Showing posts with label compensated cirrhosis. Show all posts
Showing posts with label compensated cirrhosis. Show all posts

Friday, January 6, 2017

New In Annals of Hepatology - SVR and Alcohol Consumption, Management Strategies for Liver Fibrosis and Minimal Hepatic Encephalopathy

New In Annals of Hepatology

A list of selected journal articles related to viral hepatitis published in Annals of Hepatology, January - February, 2017 issue have been provided below, view additional noteworthy articles, here.

Ongoing Alcohol Consumptions Counteracts the Benefits of Sustained Virological Response in Patients with Well Compensated Hepatitis C Cirrhosis: an Observational
Ruben Hernaez, Hashem El-Serag
No Abstract
To conclude, what should the reader tell to a well compensated hepatitis C cirrhotic patient if he/she asks "how much can I safely drink"?  The answer we believe is two fold: close to zero, and lets start you on direct antiviral agent. 
Download Full Text Article

Alcohol Intake Increases Risk for HCC in Patients With HCV-Related Cirrhosis
Alcohol consumption — including light-to-moderate — was associated with an increased risk for hepatocellular carcinoma among patients with hepatitis C virus infection-related cirrhosis, according to published findings.

Concise Review
Management Strategies for Liver Fibrosis
Alejandra Altamirano-Barrera, Beatriz Barranco-Fragoso, Nahum Méndez-Sánchez
Liver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibrosis, viral infection is most common (hepatitis B and C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages. As well as the production of other cytokines and chemokines, which increase the stimulus of hepatic stellate cells by activating proinflammatory cells. The aim of this review is to identify the therapeutic options available for the treatment of the liver fibrosis, enabling the prevention of progression when is detected in time.

Minimal Hepatic Encephalopathy in Cirrhosis- How Long to Treat?
Omesh Goyal, Sandeep S. Sidhu, Harsh Kishore
Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE. Material and methods. In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months. Results. Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn't. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse. Conclusion. Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for Study of the Liver and the Canadian Association for the Study of the Liver

Thursday, January 7, 2016

AbbVie- FDA Grants Priority Review for Supplemental NDA for VIEKIRA PAK® without Ribavirin

U.S. FDA Grants Priority Review to AbbVie for Supplemental New Drug Application for VIEKIRA PAK® (ombitasvir, paritaprevir, ritonavir tablets; dasabuvir tablets) without Ribavirin in Genotype 1b Chronic Hepatitis C Virus Patients with Compensated Cirrhosis

- The priority designation shortens the regulatory review period from the standard 10 months to six months

- TURQUOISE-III study showed 100 percent sustained virologic response at 12 weeks post-treatment (SVR12) in patients with genotype 1b (GT1b) chronic hepatitis C virus (HCV) and compensated cirrhosis (Child-Pugh A

NORTH CHICAGO, Ill., Jan. 7, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) and granted priority review for VIEKIRA PAK® (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) without ribavirin (RBV) in patients with genotype 1b (GT1b) chronic hepatitis C virus (HCV) and compensated cirrhosis (Child-Pugh A). The current dosing recommendation for patients with GT1b and compensated cirrhosis is to administer RBV with VIEKIRA PAK for 12 weeks. The FDA grants priority review designation to investigational therapies that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.

VIEKIRA PAK is a prescription medicine used with or without ribavirin to treat adults with genotype 1 (GT1) chronic HCV infection, including people who have a certain type of cirrhosis (compensated). VIEKIRA PAK is not for people with advanced cirrhosis (decompensated). If people have cirrhosis, they should talk to a doctor before taking VIEKIRA PAK.

"We are pleased that the FDA has granted priority review for VIEKIRA PAK without ribavirin as a therapy for treating GT1b chronic hepatitis C patients who have compensated cirrhosis," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "The filing of this sNDA further underscores AbbVie's commitment to patients living with chronic HCV infection."

The TURQUOISE-III study included in the sNDA evaluated the use of VIEKIRA PAK without RBV for 12 weeks in GT1b patients with compensated cirrhosis (Child-Pugh A). Results demonstrated 100 percent (N=60/60) sustained virologic response at 12 weeks post-treatment (SVR12). No patients discontinued treatment due to adverse events. The most commonly-reported adverse events (≥10 percent) were fatigue (22 percent), diarrhea (20 percent), headache (18 percent), arthralgia (10 percent), dizziness (10 percent), insomnia (10 percent) and pruritus (10 percent).1

The Centers for Disease Control and Prevention (CDC) estimates that in the United States, 2.7 million people are chronically infected with HCV.2 Genotype 1 is the most common HCV in the U.S.3 Of the total U.S. population with GT1 HCV infection, approximately 77 percent are genotype 1a (GT1a) and 23 percent are GT1b.3

About the TURQUOISE-III Study
TURQUOISE-III is a multi-center, open-label Phase 3b study to evaluate the safety and efficacy of 12 weeks of treatment with VIEKIRA PAK without ribavirin (RBV) in adult patients (N=60) with genotype 1b (GT1b) chronic hepatitis C virus (HCV) infection and compensated liver cirrhosis (Child-Pugh A) who were treatment-naïve or treatment-experienced (failed previous therapy with pegylated interferon and RBV). The primary endpoint is the rate of sustained virologic response 12 weeks after treatment (SVR12).1


Monday, July 23, 2012

Survey: Surgeons Play to Strengths in Early Hepatocellular Cancer

By: NEIL OSTERWEIL, Oncology Report Digital Network

ORLANDO – Treatment centers and surgeons tend to play to their strengths when choosing therapy for patients with well-compensated cirrhosis of the liver and early hepatocellular carcinoma, investigators reported at a symposium sponsored by the Society of Surgical Oncology.

Therapy for early HCC with well-compensated cirrhosis is controversial; there is little agreement on when resection, transplantation, or radiofrequency ablation becomes the best approach. Choice of therapy for early HCC often depends on the surgeon’s repertoire of techniques and the therapeutic services the hospital offers, based on the findings of a web-based survey of centers that had at least five HCC cases per year.

"This study demonstrates that nonclinical factors have an important effect of therapy for early HCC, and in particular the choice of therapy depends in part on the surgeon’s portfolio of techniques, as well as the availability of transplantation services," said Dr. Hari Nathan of the department of surgery at Johns Hopkins Hospital in Baltimore.

In a previous analysis of the data from their web-based survey, Dr. Nathan and colleagues found that surgeon specialty was more important than certain patient-specific factors when determining treatment choice (J. Clin. Oncol. 2011;29:619-25).

"Differences in choice of therapy for nontransplant and transplant surgeons were not the result of an across-the-board preference for one therapy vs. another. Rather, some clinical factors impacted surgeons differently, depending on their specialty," he said.

In the new analysis, the authors used the survey data to assess the effect of surgeon and hospital factors on the choice of therapy for early, well-compensated HCC, and the effect of regional liver transplantation services on the surgeon’s choice of therapy.

They defined early HCC according to the Milan criteria as a single tumor less than 5 cm in its largest dimension, or two to three tumors less than 3 cm. Cirrhosis was considered to be well compensated if it was Child-Pugh class A, with no varices, ascites, or encephalopathy.

They presented respondents with case scenarios factoring in age, tumor number and size, type of resection required, etiology of cirrhosis (hepatitis B or C, or alcoholic), biological MELD (Model for End-Stage Liver Disease) score, platelet count, and anticipated transplantation waiting time.

Of the 1,032 invitations they extended, 336 surgeons (33%) responded. Of the respondents, 284 (85%) were in academic practices and 52 (15%) were in community practices for a median of 10 years (range, 4-17 years). About two-thirds (65%) were trained in liver transplantation. Procedures performed for HCC included transplantation and radiofrequency ablation (41% of responders), transplantation alone (14%), or liver resection but not transplantation (45%). Asked which procedures were available at their primary hospital (regardless of whether the respondent performed them personally), 100% said that resections were available, and 99% said that ablations were available. In contrast, transplantations were available at 71% of respondents’ hospitals.

The authors found that neither years in practice, surgical oncology training, nor liver transplantation training had a significant effect on treatment choice. Similarly, regional transplantation variables – such as number of procedures, percentage of transplant recipients with HCC, 30th percentile of liver transplantation wait time, and severity of illness by median MELD score – did not significantly predict treatment choice.

There was, however, significant variation in therapeutic choice based on practice type, adjusted for case presentation, with surgeons in academic practices favoring transplantation 57% of the time, compared with 47% for those in community practice. Community-based surgeons were more likely to favor liver resection (45% vs. 38% for academic surgeons), and radiofrequency ablation (9% vs. 4%).

In regression analysis that controlled for clinical factors, they found that surgeons in academic setting were significantly less likely than community-based surgeons to recommend ablation over liver transplantation (relative risk ratio [RRR], 0.41; P = .01). When they looked at the effect of practice types’ controlling for surgeons’ specialties, however, the significance of the practice type on treatment choice disappeared.

Regression analysis also showed that "higher volume surgeons prefer transplantation over resection more strongly than lower-volume surgeons," Dr. Nathan said.

High-volume surgeons (defined as those performing 30 or more cases annually) were overwhelmingly transplantation surgeons; when the authors adjusted for whether the surgeon performed transplantations, the preference for transplantation disappeared.

Additionally, nontransplantation surgeons who worked at hospitals where transplantations were available were more likely to recommend transplantation over ablation, compared with surgeons working at nontransplantation hospitals.

"Interestingly, they also favored resection over radiofrequency ablation more strongly. This appeared to be a separate phenomenon than the one that we observed for the portfolio – that’s personally performed by each surgeon – and in regression analyses these effects were independent," he said.

Coauthor John F.P. Bridges, Ph.D., provided financial and administrative support for the study. Dr. Nathan reported no relevant financial disclosures.

Friday, April 20, 2012

EASL-New data from descriptive sub-analysis of patients with compensated liver cirrhosis

New data from descriptive sub-analysis of patients with compensated liver cirrhosis

New data from a descriptive sub-analysis of patients with compensated liver cirrhosis show that up to 43 percent of genotype-1a (GT1a) and up to 71 percent of GT1b hepatitis C virus (HCV) patients achieved sustained viral response (SVR12). SVR12 has been highly correlated with SVR24, which is a recognized indicator of viral cure.

This descriptive sub-analysis from SOUND-C2, a Phase 2b study evaluating interferon-free treatment with Boehringer Ingelheim's investigational direct-acting antiviral (DAA) compounds BI 201335 and BI 207127 plus ribavirin (RBV), includes HCV GT1a and 1b patients with compensated liver cirrhosis, regardless of IL-28B allele status.

Presented today (poster #1420) at the International Liver Congress™, the 47th Annual Meeting of the European Association of the Study of the Liver (EASL 2012), in Barcelona, Spain, this analysis from the SOUND-C2 study is the first dataset for an interferon-free regimen in HCV patients with compensated liver cirrhosis. SVR12 results from the SOUND-C2 study were highlighted today during an official EASL press conference and will be presented in full as part of an oral abstract session on Saturday, April 21 (oral abstract #101).

"HCV patients with cirrhosis are in urgent need of treatment to preserve liver function," said Stefan Zeuzem, M.D., Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany and one of the study investigators. "The results from this analysis of -CSOUND2 show the potential to achieve viral cure at rates similar to those seen with current therapies but without interferon in advanced genotype-1 HCV patients and warrant further evaluation."

Liver cirrhosis, where liver cells are either damaged or killed and replaced by scar tissue, causes liver function to deteriorate over time and increases the risk of liver cancer and liver transplant. In the United States, HCV is one of the most common causes of cirrhosis, with up to 20 percent of chronic HCV patients developing the condition.

"Today, one in five patients with HCV develops cirrhosis. It's important to investigate treatment options to determine if they are both effective and well tolerated in this patient population," said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Through our HCVerso™ clinical trial program, we are working with HCV experts from around the world to continue to design programs that investigate treatment with BI 201335 and BI 207127 in real-world settings, with the aim of extending a cure to more patients."

SVR12 Descriptive Sub-Analysis of Cirrhotic Patients in SOUND-C2
The SOUND-C2 open-label Phase 2b study includes 362 treatment-naive GT1 HCV patients, randomized into five interferon-free treatment groups, each with 120 mg BI 201335 once-daily (QD), but with different dosing of BI 207127 and treatment durations

This descriptive sub-analysis includes 37 patients with biopsy or Fibroscan confirmed cirrhosis. All 37 patients had compensated liver disease: 24 were GT1b and 30 had IL-28B genotype CT/TT. Patients who received the three times daily (TID) dose of BI 207127 (Arms A, B and C) were pooled.
None of the patients in this descriptive sub-analysis treated with BI 207127 twice-daily (BID) experienced relapse after treatment completion. One of the 13 patients (8 percent) in the BI 207127 TID pooled group (Arms A, B and C) of the analysis experienced relapse. Breakthrough occurred in five patients (38 percent) in the BID Arm, four patients (19 percent) in the pooled group (Arms A, B and C) and two patients (67 percent) in the BI 207127 TID Arm with no RBV (Arm E).

Seven patients (19 percent) in the descriptive sub-analysis discontinued treatment early due to adverse events (AEs), with rash, photosensitivity, and jaundice caused by isolated hyperbilirubinemia (not associated with liver dysfunction) being the most commonly reported. Four patients (19 percent) in the BI 207127 TID pooled group (Arms A, B and C) experienced serious AEs compared with two patients (15 percent) in the BI 207127 BID Arm (Arm D). No discontinuations due to rash, jaundice, or photosensitivity occurred in the BID arm of the analysis.

The investigators noted that further evaluation of interferon-free treatment with BI 201335 and BI 207127 in patients with cirrhosis is warranted.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.

Related:EASL-BI 201335 and BI 207127-Viral cure achieved without interferon in up to 82% of hepatitis C patients (GT-1a & -1b*)

EASL- First ever data investigating interferon-free treatment in hepatitis C patients who have liver cirrhosis shows high viral cure rate: protease inhibitor BI 201335 plus the polymerase inhibitor BI 207127 plus ribavirin

Sunday, December 11, 2011

Advanced Liver Disease: What Every Hepatitis C Virus Treater Should Know

Advanced Liver Disease Volume 19 Issue 3 August/September 2011

Please click below to listen to podcast and view text.

Advanced Liver Disease: What Every Hepatitis C Virus Treater Should Know

Audio Will Include Moments Of Hesitation/Silence During Podcast.....

Patients with advanced fibrosis need to be regularly monitored for evidence of decompensated disease, and complications need to be aggressively managed.....

This article summarizes a presentation by Kenneth E. Sherman, MD, at the IAS–USA live continuing medical education course, Management of Hepatitis C Virus in the New Era, held in New York City in April 2011.

Wednesday, December 7, 2011

Telaprevir Effective in Hard-to-Treat Cirrhotic HCV

Medscape Medical News from:

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting

This coverage is not sanctioned by, nor a part of, the American Association for the Study of Liver Diseases.

Telaprevir Effective in Hard-to-Treat Cirrhotic HCV

Neil Canavan

December 6, 2011 (San Francisco, California) — Adding the recently approved protease inhibitor telaprevir to pegylated interferon (peginterferon) plus ribavirin therapy achieved a 47% sustained viral response (SVR) in hard-to-treat patients with hepatitis C virus (HCV) infection and cirrhosis who had previously failed the standard 2-drug regimen. This finding comes from a subset analysis of the phase 3 REALIZE trial, presented here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.

The REALIZE investigators originally looked at telaprevir in combination with peginterferon plus ribavirin in patients with HCV genotype 1 who had had a previous null or partial response, or who had relapsed after treatment with the 2-drug regimen. REALIZE had 3 treatment groups — 2 with different schedules of triple therapy and a third with placebo plus the 2-drug regimen.

Stanislas Pol, MD, PhD, from the Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale, and Assistance Publique-Hôpitaux de Paris, Cochin Hospital, France, and colleagues performed the subanalysis of the REALIZE trial to gauge the effect of triple therapy on a subset of patients with Child class A cirrhosis who had responded poorly to the 2-drug regimen. "For this analysis, we pooled the 2 telaprevir arms since there was no difference in safety and efficacy" between the 2, he explained.

The REALIZE study population consisted of 169 patients with cirrhosis (stage F4) and 493 patients without cirrhosis (stages F0 to F3). For the entire cohort, median age was 52 years, 93% was white, 88% had an HCV RNA level of at least 800,000 IU/mL, and median body mass index was 28 kg/m². Just more than half of the patients were infected with HCV genotype 1a.

There were more null responders in the group with cirrhosis (36% vs 25%), but fewer relapsers (43% vs 57%).

Results showed that in patients with no, minimal, or portal fibrosis (F0 to F2), SVR was achieved in 75% of patients receiving telaprevir and in 22% of those receiving placebo.

"If we consider SVR according to fibrosis stage and prior response, we see no clear impact of fibrosis stage on the overall SVR rate of around 85%. For prior partial responders, there was a significant impact by fibrosis stage, with a decrease in SVR rate from 77% to 56% in patients with mild fibrosis, declining to 34% in those patients with cirrhosis," Dr. Pol told Medscape Medical News.

In previous null responders, the SVR rate after triple therapy was 41% in the patients without cirrhosis, 42% in those with mild fibrosis, and 14% in those with cirrhosis.

More than half (53%) of these previously treated patients with cirrhosis did not achieve an SVR with the addition of telaprevir, compared with 27% of patients without cirrhosis.

Regarding safety, the prevalence of rash was higher in patients with than without cirrhosis (67% vs 53%), but other rates for common adverse events were similar. For hematologic events, anemia was more frequent in patients with cirrhosis (42% vs 34%). In addition, neutropenia was higher (25% vs 17%) and, "as might be expected, platelet counts were lower in the cirrhotic subset," Dr. Pol noted.

Can Early Responders Stop Treatment?

The relatively high response rate in patients with cirrhosis and HCV who had failed previous treatment with peginterferon and ribavirin raises the question of whether treatment can be stopped early with triple therapy.

Michael Bernstein, MD, director of the hepatitis clinic at the Coney Island Hospital, Brooklyn, New York, asked: "If they had an extended RVR [rapid virologic response], if they were negative for virus at week 4 and again at week 12, for which there was evidence in REALIZE, then perhaps they could get just 24 weeks of treatment. That's called response-guided therapy."

Dr. Bernstein's reasoning is that in patients without cirrhosis, an extended RVR is indicative of a greater than 90% SVR rate.

"The current recommendation is to treat these patients for 48 weeks, whether they have an extended RVR or not. In this study, this is a special subgroup of patients — even a sub-subgroup — because it is not just cirrhotics, but cirrhotics who have not responded previously to treatment.... It may be feasible to stop [treatment] at 24 weeks if they have this very favorable RVR," he told Medscape Medical News. As phase 4 data accrue, evidence might support doing so.

Dr. Pol reports being a consultant for Bristol-Myers Squibb, Boehringer Ingelheim, Tibotec, Novartis, and Gilead; and receiving grants for research from Bristol-Meyers Squibb, Gilead, Roche, and Schering-Plough/Merck. Dr. Bernstein has disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 31. Presented November 6, 2011.

Monday, August 22, 2011

Hepatitis C in HIV-infected Patients With Compensated Liver Cirrhosis

From Journal of Viral Hepatitis
Treatment of Chronic Hepatitis C in HIV-infected Patients With Compensated Liver Cirrhosis
L. Martín-Carbonero; P. Tuma, E. Vispo; J. Medrano, P. Labarga; J. González-Lahoz; P. Barreiro; V. Soriano
Authors and Disclosures
Posted: 08/22/2011; J Viral Hepat. 2011;18(8):542-548. © 2011 Blackwell Publishing

Abstract and Introduction
Patients and Methods

Treatment of chronic hepatitis C has often been declined in HIV–HCV-coinfected patients, mainly because of concerns about poor tolerability of peginterferon–ribavirin and relatively low treatment responses. Moreover, alcohol and/or intravenous drug abuse, neuropsychiatric conditions and poor social environment have all contributed to the low implementation of HCV therapy in this population.[23,24] Given that HCV-related liver fibrosis progress faster in HIV-positive individuals,[11] a growing number of coinfected patients currently present with liver cirrhosis. Current estimates suggest that half of patients older than 50 years who acquired HIV and HCV more than 25 years earlier will show cirrhosis.[25,26] Information on the efficacy and safety of peginterferon–ribavirin in this subset of patients is scarce. This information is important because the risk of liver failure is higher in cirrhotic patients with HIV infection[27,28] and clearance of HCV as a result of successful therapy is the best way to prevent liver decompensation in these patients.[12,15] In this regard, it is encouraging that our study conducted in HIV–HCV-coinfected patients showed a similar rate of SVR and side effects in 41 compensated cirrhotics compared to 190 noncirrhotics, all of whom had been treated with peginterferon–ribavirin. This is in contrast with prior reports, which have reported lower SVR rates and poorer tolerability in patients with advanced fibrosis and cirrhosis. However, this information was mainly drawn from retrospective analysis of the relatively small subset of cirrhotic individuals enrolled in trials conducted either in HCV-monoinfected[16,17,29] or coinfected individuals.[18,19,30] In fact, although the presence of bridging fibrosis and cirrhosis was a predictor of non-SVR in the univariate analysis in some of these studies, only in one of them remained associated with nonresponse in the multivariate analysis.[16] In this respect, a more recent study that compared HCV treatment outcomes in patients with cirrhosis and noncirrhotic monoinfected patients,[31] greater SVR rates were seen in noncirrhotic patients, but cirrhotics were significantly older and had higher body mass index, which most likely explained the results. In fact, in the multivariate analysis only infection with HCV genotypes 1–4 and high-baseline serum HCV-RNA remained as independent predictors of nonresponse.
Even in the face of potential low response rates and poorer tolerability, the benefits of curing hepatitis C in patients with cirrhosis have to be highlighted.[32] HCV clearance following successful treatment is associated with a halt and even reversion of liver fibrosis,[12,33] a reduced risk of liver decompensation events[13–15,34] and most likely a diminished chance of developing hepatocellular carcinoma.[15,34] In this regard, our results demonstrating a similar performance of peginterferon–ribavirin in patients with cirrhosis and noncirrhotics should encourage the consideration of HCV treatment in all HIV–HCV-coinfected patients with cirrhosis in the absence of any serious contraindication for HCV medications.

Liver decompensation may be precipitated following the initiation of peginterferon–ribavirin therapy in subjects with advanced fibrosis, especially in the setting of HIV infection and concomitant antiretroviral therapy.[35] In our study, only one of 41 patients with cirrhosis experienced a liver decompensation event after initiating HCV therapy. It is now clear that avoidance of potentially deleterious drug interactions and careful monitoring of liver function may significantly reduce clinical hepatic events during HCV therapy. Accordingly, none of the 389 coinfected patients enrolled in a recent HIV–HCV therapeutic trial developed liver decompensation, despite 27% of them having baseline F3–F4 Metavir fibrosis scores.[18]
It should be noticed that patients infected with HCV genotypes 1 and 4 showed a relatively low SVR rate (≤35%), regardless of being cirrhotics or not. In contrast, in patients infected with HCV genotypes 2 or 3, SVR rates tended to be higher in noncirrhotic than in individuals with cirrhosis (68%vs 50%, respectively), most likely reflecting a slightly poorer tolerability of the HCV medication in the latest group. In agreement with other trials,[36] in our study, cytopenias and specially thrombocytopenia were the most common treatment limiting side effect and mainly were seen in cirrhotics, forcing drug dose reductions and occasionally treatment withdrawal. Thus, close monitoring of platelet counts and consideration of strategies to prevent and manage thrombocytopenia (e.g., using eltrombopag) should be examined in this population.

Assessment of liver fibrosis before prescription of HCV therapy is increasingly being made using noninvasive tools and replacing liver biopsy. Information on treatment outcomes in the subset of patients with cirrhosis in older studies was mainly derived from fibrosis staging using liver biopsy.[16,17,19,29,30] In our study, elastometry was used to differentiate subjects with liver cirrhosis from the rest. This new method has shown to accurately predict cirrhosis when compared with other approaches, as liver biopsy or serum fibrosis indexes.[21,22,37–41] A wide use of noninvasive tools for assessing liver fibrosis will facilitate the recognition of the subset of chronic hepatitis C patients with advanced fibrosis in whom HCV treatment consideration is warranted. Unfortunately, therapeutic considerations so far often have been based on liver enzyme elevations, which do not reflect liver damage, especially in the HIV setting.[42,43]
Our study has some limitations. As this is a retrospective study, some data as HCV treatment dose reduction or heavy alcohol intake could not be properly recorded. The former information would have been important in terms of SVR. Baseline characteristics had also some differences, patients with cirrhosis had lower CD4 cell counts and were more often on HAART. We believe that does not reflect longer duration of HCV or HIV infection in this population, as the rest of epidemiological characteristics (median age, route of infection, etc) were similar between groups. Even more, the worst HIV characteristics among patients with cirrhosis will bias them towards lower SVR rates, which was not the case.

In summary, our results proving that treatment outcomes in HIV–HCV-coinfected patients with cirrhosis are similar to those obtained in noncirrhotic individuals support that HCV treatment should be offered to all patients with compensated liver disease as long as no serious contraindications for using HCV medications are acknowledged. However, closer monitoring of cytopenias, mainly platelet counts, may be warranted in the subset of patients with liver cirrhosis undergoing HCV therapy.

View Full Data Here

Friday, July 29, 2011

Chronic hep C treatment in HIV-infected patients with compensated liver cirrhosis

Chronic hep C treatment in HIV-infected patients with compensated liver cirrhosis

Sustained virological response was associated with HCV genotypes 2–3
Journal of Viral Hepatitis

The most recent issue of the Journal of Viral Hepatitis investigates treatment of chronic hepatitis C in HIV-HCV coinfected patients with compensated liver cirrhosis.
The greatest benefit of hepatitis C virus (HCV) therapy is seen in cirrhotics attaining sustained virological response.
However, concerns about toxicity and poorer responses often discourage treatment of cirrhotics.
This may be particularly relevant in HIV–HCV-coinfected patients, in whom progression of liver fibrosis is faster and treatment responses lower.

Dr Luz Martin-Carbonero and colleagues from Spain performed a retrospective analysis of HIV–HCV-coinfected patients who had received peginterferon–ribavirin therapy at their institution.

Individuals naïve for interferon in whom liver fibrosis had been assessed using elastometry within the year before being treated were chosen.

Response rates and toxicities were compared in cirrhotics and noncirrhotics.
Patients with previous liver decompensation were excluded.

Overall, the team found that 41 cirrhotics and 190 noncirrhotics entered the study.
Groups were similar in age, gender, HCV genotypes and baseline serum HCV-RNA.

The research team observed that sustained virological response occurred at similar rates in cirrhotic and noncirrhotics, either considered by intention-to-treat or as treated.

The researchers found that sustained virological response was associated with HCV genotypes 2–3 and lower serum HCV-RNA but not with cirrhosis.

The team noted that treatment discontinuations because of adverse events tended to be more common in cirrhotics than in noncirrhotics, but only severe thrombocytopenia was more frequent in cirrhotics than in non-cirrhotics.

Dr Martin-Carbonero's team concluded, "Response to peginterferon–ribavirin therapy is similar in HIV–HCV coinfected patients with and without liver cirrhosis."
"Therefore, treatment must be encouraged in all compensated cirrhotic patients, although closer monitoring and management of side effects, mainly thrombocytopenia, may be warranted."

J Viral Hep 2011: 18(8): 542–548
29 July 2011

Thursday, April 7, 2011


EASL; Session Title: Category 02b: Cirrhosis and its complications: Clinical aspects

Presentation Date: 31 MAR, 2011


V. Calvaruso1*, V. Di Marco1, D. Ferraro2, P. Pizzillo2, G. Alaimo1, A. Craxì1

1Gastroenterology and Hepatology, 2Igiene e Microbiologia, University of Palermo, Palermo, Italy. *

Background and aim: To assess the virological and disease factors associated to liver related events and survival in patients with compensated HCV cirrhosis treated with interferon based therapy.

Patients and methods: A cohort of 425 patients with Child-A HCV cirrhosis (mean age 58.0±8.5 years, 61.9% males; 87.1% infected by HCV-Genotype1 and 12.9% by Genotype2/Genotype3; 52.8% with esophageal varices, 27.5% with diabetes) received interferon-based antiviral treatment.

Sustained Virological Response(SVR) was defined as HCV-RNA negative at 6th month of follow-up. All patients underwent ultrasound scan every 6 months and endoscopy were repeated every 2 years.

Results: Overall SVR was 23.8% (17.6% in Genotype 1 patients vs 65.5% in Genotype2/Genotype 3 patients).

During a median follow-up of 48 months, 77 patients (18.1%) developed liver decompensation, 50 patients (11.8%) had hepatocellular carcinoma (HCC) and 55 patients(12.9%) died for liver events.

By Log-Rank test presence of esophageal varices (EV) was statistically associated to an higher occurrence of liver decompensation (p< 0.001) and with mortality liver related (p=0.009), but not with development of HCC (p=0.07).

The absence of SVR was associated with an higher rate of liver decompensation(p< 0.001), HCC(p< 0.001) and mortality(p=0.001).By Cox regression analysis, albumin (OR:0.61, CI95%:0.37-0.98; p=0.043), Bilirubin (OR:1.50, CI95%: 1.02-2.21; p=0.040), platelet count(OR:0.99, CI95%: 0.98-0.99; p=0.005) and SVR (OR:0.26, CI95%: 0.09-0.72; p=0.009) were independently associated with mortality. Adding decompensation and HCC development to the model these two variables became the unique factors independently associated to mortality liver related (OR:4.05, CI95%: 2.27-7.22; p< 0.001) and (OR:3.80, CI95%: 2.21-6.55; p< 0.001) respectively.

Conclusion: In patients with compensated HCV-cirrhosis, the presence of esophageal varices is associated with higher rate of decompensation and mortality but not with HCC occurrence.

SVR is a favourable factor of free-of-event survival by univariate analysis but only the liver events occurrence is independently associated to mortality. Development of HCC doesn't act only as a decompensation hastener but it results independently associated to mortality.

Friday, December 10, 2010

Increased risk of hip and wrist fracture in patients with cirrhosis compared with the general population

Increased risk of hip and wrist fracture in patients with cirrhosis compared with the general population: a population-based cohort study

Joe West1, Zahid Asghar1, Guruprasad P. Aithal2, Tim R. Card1, 3, Kate Fleming11. Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom. 2. Nottingham Digestive Diseases Centre, Biomedical Research Unit, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom. 3. Department of Gastroenterology, Kings Mill Hospital, Sutton, Ashfield, United Kingdom.


While numerous studies have shown an association between chronic liver disease and osteoporosis few have documented accurately the risks of osteoporotic fracture in these patients and none have compared incidence rates to the general population. We have therefore performed a cohort study using the General Practice Research Database (GPRD) to quantify the excess fracture risk in people with cirrhosis.


We obtained all records of patients with a diagnostic of therapeutic code for cirrhosis, oesophageal varices and/or portal hypertension within the
General Practice Research Database=GPRD between June 1987 and April 2002 and records of up to 10 age-, sex- and practice matched controls.
We examined hazard ratios of hip and wrist fracture rates for patients with cirrhosis versus general population controls using cox proportional hazards, adjusted for age at entry to the study and sex. Analyses were stratified by aetiology of cirrhosis and severity of disease.

Patients with cirrhosis had a higher hazard of hip and wrist fracture
*see table 1
Patients with alcoholic cirrhosis had a higher hazard ratio for fractures than patients with non-alcoholic related cirrhosis.
However, this is mediated by increased risk of fracture in older control population on non-alcoholic related cirrhosis
*see table 2
A total of 4787 subjects with cirrhosis and 46,789 appropriately matched controls contributing 205,852 person years of follow-up were included within our analysis.
Main results are displayed in the table below.
There was a 4-fold increased hazard of hip fracture and nearly 2-fold increased hazard of colles fracture for the cirrhosis cohort compared with the general population.

Rates were higher for patients with decompensated disease than those with compensated cirrhosis. Absolute fracture rates in patients with alcoholic cirrhosis and non-alcohol related cirrhosis were very similar at 5.2 and 5.1 per 1000 person years respectively.

The difference in hazard ratios can be largely attributed to the older age of the patients with non-alcohol related cirrhosis and therefore the higher risk of fracture in their control population.
, .


There are large relative increases in fracture risks in people with cirrhosis compared with the general population.
The absolute excess rates we have observed mean that consideration should be given to interventions in this group to reduce fracture risk.
Abstract # 1180. AASLD 2010

Wednesday, November 10, 2010

2010 Hepatitis C:After 30yrs 15%–35% will develop cirrhosis

Prevalence and Challenges of Liver Diseases in Patients with Chronic Hepatitis C Virus Infection

Ira M. JAcobson; Gary L. Davis; Hashem El–Serag; Francesco Negro; Christian trépo
Posted: 11/09/2010; Clin Gastroenterol Hepatol. 2010;8(11):924-933. © 2010 AGA Institute

Abstract and Introduction

Hepatitis C virus (HCV) infections pose a growing challenge to health care systems. Although chronic HCV infection begins as an asymptomatic condition with few short-term effects, it can progress to cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and death. The rate of new HCV infections is decreasing, yet the number of infected people with complications of the disease is increasing. In the United States, people born between 1945 and 1964 (baby boomers) are developing more complications of infection. Men and African Americans have a higher prevalence of HCV infection. Progression of fibrosis can be accelerated by factors such as older age, duration of HCV infection, sex, and alcohol intake. Furthermore, insulin resistance can cause hepatic steatosis and is associated with fibrosis progression and inflammation. If more effective therapies are not adopted for HCV, more than 1 million patients could develop HCV-related cirrhosis, hepatic decompensation, or HCC by 2020, which will impact the US health care system. It is important to recognize the impact of HCV on liver disease progression and apply new therapeutic strategies.

Approximately 180 million people worldwide are infected with hepatitis C virus (HCV)[1] and are at risk of developing serious hepatic complications such as cirrhosis, hepatocellular carcinoma (HCC), or decompensation. In the United States, HCV-related end-stage liver disease is the most common indication for transplantation,[2] and HCV markers are frequently found in cases of HCC.[3,4] Although some data suggest that hepatitis C does not increase overall mortality,[5] it has been postulated that HCV infection could result in an 8- to 12-year reduction in life expectancy.[6] It is estimated that HCV caused more than 86,000 deaths in the European region in 2002.[7] The prevalence of hepatitis C–related cirrhosis and its complications is expected to continue to increase through the next decade.[8] In addition, demographic changes are expected to result in an increasing incidence of severe HCV-related liver disease as the population ages.

Less than half (42%–46%) of patients infected with HCV genotype 1,[9,10] the major genotype in the USA,[11] achieve a sustained virologic response (SVR) with currently available treatment (peginterferon/ribavirin for 48 weeks). There is also evidence to suggest that HCV infection is both underdiagnosed and undertreated.[12–14] The lack of access to effective, welltolerated therapies has serious implications for the current and future burden of HCV. A recent report commissioned by the Institute of Medicine (IOM) of the National Academies highlighted shortcomings in care for viral hepatitis, including the estimate that up to 75% of HCV-infected persons have not even been diagnosed. The report includes sweeping recommendations for prevention, identification, control, and surveillance of HCV in the general population and identifies major gaps in services for specific populations that are disproportionately affected.[15]
In light of the public health threat posed by HCV, efforts are needed to heighten awareness of its impact on patients. Numerous extrahepatic morbidities are associated with HCV infection; these and their consequences are reviewed elsewhere.[16] Here we summarize the latest evidence for the burden of chronic hepatitis C (CHC) in the United States, focusing on hepatic complications

Evidence Acquisition
This review reflects the detailed discussion and opinions of the authors (not the meeting sponsor, Vertex Pharmaceuticals Incorporated) on key articles from the published literature at an advisory board meeting on the burden of liver disease in HCV infection held in Boston, MA, in July 2007. Before the meeting, MEDLINE searches via the PubMed interface were designed and conducted by Paula Michelle del Rosario, a professional medical writer at Gardiner-Caldwell Communications. The searches encompassed the epidemiology and/or burden as a result of HCV-related liver disease by using the Medical Subject Headings (MeSH) [hepatitis C] and either [epidemiology], or [incidence], or [prevalence], or [fibrosis AND epidemiology], or [fibrosis AND mortality], or [liver cirrhosis AND epidemiology], or [liver cirrhosis AND mortality], or [carcinoma, hepatocellular AND epidemiology], or [carcinoma, hepatocellular AND mortality], or [cholangiocarcinoma OR intrahepatic cholangiocarcinoma AND epidemiology], or [fatty liver AND epidemiology], or [fatty liver AND mortality]. Articles not published in the English language and editorials, correspondence, letters, comments, and news articles were excluded. The authors received the search terms and results of the searches in advance of the meeting, and they selected relevant articles for discussion. The authors were responsible for several additions to content and topics covered. Throughout the development of the manuscript, the authors were personally responsible for a marked expansion in the scope of the article, including new references and concepts published since the original advisory board, making this essentially a new article. In addition, the manuscript was thoroughly updated with a repeated PubMed search by Gardiner-Caldwell Communications in September 2009 to capture articles published since the original search was conducted, and relevant publications were selected for inclusion by the authors.

Prevalence, Identification of at-risk Individuals, and Effects on Life Expectancy
Various estimates of HCV prevalence in the US population place the number of infected individuals (as defined by anti-HCV antibody positivity) at between 4.1 and 5 million. Of these, 3.2–3.4 million are chronically infected.[17,18] During the first 10–20 years of infection HCV-infected individuals generally experience asymptomatic or mild illness,[19] which explains why an estimated 75% of infections remain undiagnosed in the United States.[15,20] Despite a decline in the number of new US cases of HCV infection from a peak of an estimated 262,000/year in 1986 to 17,000/year in 2007,[21] the prevalence of individuals infected with HCV for more than 20 years is expected to continue to increase until 2015.[22] In the National Health and Nutrition Examination Survey (NHANES; 1999–2002), patients aged 40–49 years accounted for 66% of American HCVinfected patients, and the prevalence of HCV infection in the United States was 2.7 times higher among 40- to 49-year-olds than the general population (Figure 1).[17] This "baby boomer" generation is particularly susceptible to blood-borne HCV transmission as a result of an increased lifetime risk of injection drug use (IDU), blood transfusion before 1992, or sexual activity with ≥20 partners, compared with older or younger patients.[23,24] The prevalence of HCV infection varies by age, sex, and race/ethnicity, and early identification of at-risk individuals through routine questioning by clinicians is critical, because management options are limited in late-stage disease.[24]

Figure 1.
Prevalence of HCV antibodies by age group (A) and year of birth (B) in the 1988–1994 and 1999–2002 NHANES. Vertical bars, 95% confidence intervals. Adapted with permission from Armstrong et al 2006.17

After 30 years of infection, an estimated 15%–35% of patients will develop cirrhosis (5-year survival, 75%–80%);[6] after 40 years, up to 60% could have cirrhosis.
Given the high prevalence of HCV infection among 40- to 49-year-olds[17] and that Americans are now expected to live into their mid-70s or beyond, the incidence of complications of HCV infections can be expected to further increase in coming years. In fact, from 1995–2004, US HCV-related mortality already increased 123% from 1.09/100,000 to 2.44/100,000 persons, although this study has some limitations.[25] Furthermore, the proportion of CHC patients in the United States with cirrhosis is projected to rise from 25% in 2010 to 45% in 2030.[8] Projections also estimate that without effective treatment, the annual number of US patients with cirrhosis, hepatic decompensation, or HCC will roughly double by 2020, and liver-related deaths will almost triple (Table 1).[26] Although not all data agree with these estimates,[5] several studies have suggested that HCV infection could have a deleterious effect on population mortality rates and life expectancy.[27,28] HCV increased the risk of death in several analyses, irrespective of comorbidities such as coinfection with human immunodeficiency virus (HIV)[29] or hepatitis B virus (HBV)[30,31] and even after adjustment for alcohol consumption.[32] Furthermore, numerous studies[33–37] and a Cochrane review[38] indicated that achievement of an SVR through effective antiviral therapy can significantly reduce mortality in patients with chronic HCV. If all HCV-infected patients were treated with currently available treatment in 2010, liver-related HCV-associated deaths could be reduced by 36% by 2020,[8] whereas antiviral treatment rates are currently declining. Improvements in diagnosis and treatment are therefore necessary to reduce the associated public health burden.[15,39]

Hepatic Consequences
Individuals with CHC are at increased risk of liverrelated morbidity and mortality. HCV infection was associated with 27% of all US liver transplants performed in 2007,[2] and US-based studies demonstrated that up to 51%–55% of HCC patients have anti-HCV antibodies.[3,4] There is also a link between steatosis and liver fibrosis in HCV-infected patients,[40] as well as a potential association between HCV infection and HCC or, as described more recently, of intrahepatic cholangiocarcinoma (ICC).[41–45] In some ethnic groups such as Latinos the course of HCV infection is more aggressive, with a higher risk of cirrhosis than other ethnic groups.[46] Furthermore, disease progression is more rapid in patients who are coinfected with HCV and HIV. Coinfected patients have approximately double the risk of cirrhosis or decompensation than those infected with HCV alone.[47]

Fibrosis and Cirrhosis
Progressive hepatic fibrosis leading to cirrhosis is the major complication of chronic HCV infection and accounts for almost all HCV-related morbidity and mortality.[26] Early studies suggested little, if any, fibrosis progression during the first decade of infection, followed by a slow, regular progression during the next 15 years, increasing to an intermediate rate during the subsequent decade.[48,49] In a German cohort study of 1833 women infected with HCV-contaminated immunoglobulin, 0.5% of patients developed cirrhosis after 25 years.[50] Similarly, in a study of 376 HCV-infected women conducted by the Irish Hepatology Research Group, 51% of patients had fibrosis after 17 years, but only 2% had probable/definite cirrhosis.[51] These estimates of cirrhosis rates are considerably lower than those from the US multicohort study[8] and the widely cited US military study (approximately 35%).[5] Fibrosis outcomes of 184 women from the same cohort were followed up for the subsequent 5 years; 49% showed no change in fibrosis, 24% showed regression, and 27% showed progression.[52]
Recent data reinforce the potential for severe liver disease to develop in some patients. Among 485 plasma donors infected during the early 1970s, 34% had stage F3/F4 fibrosis (bridging fibrosis), cirrhosis, or HCC after 31 years; their 35-year cumulative survival was 84% versus 91%–95% for the general population.[53] Similarly, a study of 300 black and white Americans with untreated HCV infection found that 29% of patients had stage F3/F4 fibrosis after 20 years, and 4.7% had confirmed cirrhosis.[54] It should be noted, however, that these studies could have selected patients with severe disease.

The nonlinear progression of fibrosis was recently confirmed in a meta-analysis of 111 HCV studies.[55] The mean annual stage-specific transition probabilities were 0.117 for stage F0 to F1, 0.085 for F1 to F2, 0.120 for F2 to F3, and 0.116 for F3 to F4. Although the estimated prevalence of cirrhosis was 16% after 20 years, there was wide variation between studies, suggesting that fibrosis is a highly unpredictable process.

Infection duration is a major risk factor for severe fibrosis,[55] with the progression rate in a 50-year-old being almost 3 times that in a 20-year-old.[56] Age at time of infection is also important. In a biopsy analysis of 247 treatment-naïve HCV patients, progression rates were 0.13, 0.14, 0.27, and 0.36 fibrosis units/year for patients aged ≤19, 20–24, 25–36, and >36 years at infection, respectively.[57] Age >36 years (vs ≤36 years) at time of infection was independently associated with faster progression. Men infected before age 50 have been identified as comprising the majority of cases of cirrhosis today (73.6%), whereas men aged >50 years when infected have faster disease progression compared with other age groups.[8]

Several other factors, including sex, baseline fibrosis, HCV genotype, HIV/HBV coinfection, and alcohol consumption, also influence fibrosis progression (Table 2).[54–69] Identifying these factors can be useful when determining prognosis and advising patients on minimizing liver damage. Indeed, a recent study suggested that HCV genotype 3 might pose a particularly high risk of progressive fibrosis.[69] Insulin resistance has been linked with fibrosis,[70,71] and several studies have reported that this relationship remains significant, irrespective of HCV genotype.[62,72,73] In addition, serum aminotransferase level elevations and the degree of hepatocellular necrosis/inflammation on biopsy have been found to predict fibrosis progression.[74] Genetic factors might also play a role in fibrosis progression.[75,76] Recent data indicate that the cirrhosis risk score, which is based on the association of 7 host genes, might help to differentiate HCV patients at high versus low risk of progressing toward cirrhosis, including those with early or mild CHC.[76–78] Steatosis has also been linked to fibrosis progression,[40,67,79] as has regular cannabis use.[68,80] There is evidence of an association between cigarette smoking and hepatitis fibrosis,[81] but not all studies have verified such an association.[82]

Hepatocellular Carcinoma
The greatest increase in US cancer deaths from 1995–2004 was in those caused by cancers of the liver and bile duct, of which HCC comprised about 76%.[83] This might be attributed to the increasing incidence of HCV-related HCC because rates for HBVrelated and alcohol-related HCC have remained stable during recent years.[84,85] The incidence of HCV-related HCC in the United States is projected to peak in 2019 at 14,000 cases/year.[8] In a large US database, the proportion of HCV-related cases of HCC among HCC patients aged ≥65 years doubled from 11% in 1993–1996 to 21% in 1996–1999.[84] During the past decade, the fastest increase in HCC incidence has affected Hispanics and whites.[86] In multivariate analysis HCV infection was an independent predictor for the development of HCC.[87] Furthermore, maintenance therapy with peginterferon did not reduce the 5-year incidence of HCC in the HALT-C cohort.[88]

Comparisons of US and Japanese HCV strains suggest that the US HCV epidemic began about 2 to 3 decades after that in Japan.[89,90] This has led to speculation that the burden of HCC in the United States might eventually equal that currently seen in Japan as HCV-infected individuals age and their infection duration increases. In Japan, HCV-related HCC accounts for 80% of all HCC cases,[91] and the rate of HCC among HCV-infected men has risen from 17.4/100,000 in 1972–1976 (32,335 deaths) to 27.4/100,000 in 1992–1996 (109,365 deaths).[92]

A recent Italian study of 214 HCV-infected patients with Child–Pugh class A cirrhosis showed that HCC developed at a rate of almost 4%/year.[93] HCC was the first complication to occur in 55 (27%) patients; after 17 years, HCC had developed in 68 (32%) patients.[93] In another cohort of 416 patients with uncomplicated Child–Pugh class A HCV-related cirrhosis, the incidence of HCC was 13.4% at 5 years, and the 5-year HCC death rate was 15.3%, with the hazard rate of HCC tending to increase over time.[94]

Several factors influence the risk of HCC in patients with HCV-related cirrhosis. Generally, HCC risk is increased in patients aged >50 years or those infected when aged >50 years, patients with longer duration of infection, men, overweight or diabetic patients, and patients with advanced cirrhosis or elevated alpha-fetoprotein.[8,95,96] Other possible risk factors include the presence of steatosis,[41] HCV genotype 1b,[97] Asian/African American race,[98] and occult HBV infection.[99] As for hepatic fibrosis, an association between cigarette smoking and HCV-related HCC has been suggested in some studies[100] but not others.[101]

Chronic HCV-related inflammation might increase HCC risk by shifting hepatocytic transforming growth factor– beta signaling from tumor suppression to fibrogenesis.[102] HCC generally develops after cirrhosis is established, signifying the likely importance of long-standing necrosis and regeneration, an environment of extensive scarring, in its pathogenesis. HCV might influence hepatocarcinogenesis through the oncogenic effects of its core protein, which might augment oxidative stress.[103] It might also alter the signaling cascade of mitogen-activated protein kinase and activating factor 1, thereby activating cellcycle control. Liver angiogenesis and the neovascular response,[104,105] plus genomic changes that deregulate components of the Jak/STAT pathway in early carcinogenesis,[106] might also promote HCV-related hepatocarcinogenesis. Additional mechanisms have also been proposed.[107]

Various small studies have demonstrated a link between HCV and ICC.[42–45] A recent large cohort study of >140,000 HCV-infected military veterans[108] showed a >2-fold increase in ICC risk in HCV-infected patients versus noninfected controls. However, many of these hospital-based, case-control studies are limited by the potential for selection or ascertainment bias,[108] and some studies have failed to observe any association between HCV and ICC.[109,110] The association of HCV infection with susceptibility to ICC, and the pathogenetic basis for such an association, warrant further investigation. Chronic HCV infection was not a risk for extrahepatic cholangiocarcinoma (ECC).[111]

Patients with HCV-associated cirrhosis are at high risk of developing hepatic decompensation, manifesting as hepatic synthetic dysfunction or complications of portal hypertension. Clinical signs of decompensation include ascites, encephalopathy, and upper gastrointestinal hemorrhage caused by variceal bleeding.[93,112]

In an analysis of data from 1000 HCV patients with mild to advanced fibrosis, the incidence of decompensated cirrhosis after 5–7 years of follow-up was 43.5/10,000 person-years or about 1 in 230 patients/year.[65] Similarly, a retrospective study reported the 5-year risk of decompensation to be 18% in 384 HCV patients with compensated cirrhosis (incidence, 3.9%/year),[112] and a recent estimate suggests decompensation is currently present in 11.7% of CHC patients with cirrhosis.[8] Decompensation has become more common since 1995, and because the proportion of CHC patients with cirrhosis is expected to increase through 2030, the incidence of decompensation can be expected to increase accordingly.[8] It should be noted, however, that this model estimates that the majority of cirrhotic patients with chronic HCV infection will not develop decompensation during the first 3 decades of infection. Annual incidence rates for ascites (2.9%), jaundice (2.0%), upper gastrointestinal bleeding (0.7%), and encephalopathy (0.1%) were established in a later prospective study of 214 HCV-RNA seropositive patients after 114 months of follow-up.[93]

Age at HCV acquisition is relevant, with decompensation risk as high as 133/10,000 person-years in patients infected after 39 years of age.[65] In addition, the presence of the human leukocyte antigen DRB1*1201–3 allele might be associated with a higher rate of progression toward decompensated cirrhosis and HCC.[65] The identification of reliable proteomic/genomic markers for risk of advanced HCV-related liver disease would aid prognostication and therapeutic decision-making.

Steatosis occurs to some degree in about half of all patients with chronic HCV infection.[40,113] In a meta-analysis of data from >3000 patients, steatosis was independently associated with the presence of fibrosis, diabetes, hepatic inflammation, ongoing alcohol abuse, overweight (body mass index >25), age ≥45 years, and genotype 3 infection.[40] Among 101 HCV-infected patients with no factors predisposing to fatty liver, steatosis was found in 41% of patients, irrespective of sex, age, or infection route.[114]

Two main mechanisms underlie the pathogenesis of steatosis in HCV-infected patients who abstain from alcohol, a direct viral effect and a metabolic mechanism. Viral steatosis is associated with genotype 3 HCV infection,[40,114–117] where the severity of steatosis correlates with serum[71,115] and intrahepatic[113] viral load. This type of steatosis often resolves after viral eradication.[116–118] It is believed that HCV genotype 3 has a direct effect on hepatocyte lipid metabolism, resulting in fat accumulation. Interactions involving the HCV genotype 3 core protein, such as enhanced fatty acid synthase promoter activation[119] and increased lipid affinity,[120] are being investigated in vitro.

Metabolic steatosis is seen primarily in patients infected with genotype non-3 HCV[40,72] and is largely due to insulin resistance,[62,72,121] characterized by hyperinsulinemia and free fatty acid overflow to organs and non-adipose tissues.[122] These alterations give rise to triglyceride accumulation in hepatocytes, resulting in steatosis.[40,70,71,123]
Steatosis might reduce the likelihood of achieving SVR with HCV treatment, even when other steatosis-inducing factors are accounted for. In one study, SVR rates were 18%–32% lower in people with steatosis versus those without steatosis after adjusting for other potentially confounding cofactors such as genotype, fibrosis score, and viral load.[117]

Reducing the Impact of Infection
About 85% of HCV-positive persons in the United States general population can be identified on the basis of 3 characteristics: IDU history, blood transfusion before 1992, or abnormal serum alanine transaminase levels.[17] In selected populations, other characteristics might also be useful for screening. A retrospective study of 5400 US veterans found that the following factors predicted HCV infection: IDU, blood transfusion before 1992, service during the Vietnam war, tattoo, and a history of abnormal liver test results.[123] However, HCV risk factor histories are rarely documented in clinical practice.[124] Infected patients can thus remain undiagnosed until they present with hepatic complications. Recent guidelines issued by the American Association for the Study of Liver Diseases (AASLD) make recommendations for diagnosis and counseling of HCV-infected patients on alcohol, weight loss, and treatment to prevent the development of cirrhosis and other complications.[125]

Diagnosis and Screening
Figure 2 summarizes the clinical management of patients at risk of HCV infection. Asking patients about their transfusion history and high-risk drug/sexual behavior during health care visits should be routine, and high-risk patients (history of IDU, blood transfusion before 1992, or HIV-positive) should be tested, with cognizance of the higher prevalence rates in men, "baby boomers," and African Americans. The AASLD guidelines promote screening in at-risk populations to reduce HCV transmission rates.[125] The recent IOM report on viral hepatitis includes a recommendation that federally funded US health care insurers improve access to HCV screening as part of preventative care for the general population, so people at risk of HCV infection can be identified.[15]

Figure 2.
Summary of the screening, diagnosis, and treatment of patients at risk of HCV infection
Once diagnosed, patients should be evaluated for HCV RNA, genotype, and serologic exclusion of common liver diseases. Baseline imaging (ultrasound) might also be useful. Assessing fibrosis by liver biopsy can be used to estimate prognosis, treatment urgency, and necessity of HCC screening. Surrogate methods, including serum fibrosis markers, imaging techniques, and indirect methods to measure liver stiffness such as transient elastography,[125] might have a future role.

Because insulin resistance enhances fibrosis progression, monitoring insulin resistance, fasting glucose, or insulin levels is advisable. In addition, lifestyle modifications, including weight loss and dietary changes, might reduce insulin resistance and slow the fibrosis rate. All patients should be assessed for immunity against hepatitis A/B by assessment of disease markers and vaccinated if seronegative.[125] Counseling should be offered regarding alcohol consumption, if appropriate.
Currently, the only drugs available to treat HCV are peginterferon and ribavirin. SVR rates associated with peginterferon/ribavirin are suboptimal, particularly for genotype 1–infected patients.[9,10] The AASLD guidelines recommend an individualized treatment approach based on assessment of comorbidities, likelihood of response, and side-effect potential.[125] Although more effective options are needed, successful treatment can eradicate the virus and thereby minimize complications and possibly improve mortality rates.[126,127] Nearly all patients (99.2%) maintain undetectable HCV loads 5 years after attaining SVR, representing a "virologic cure."[126] Some patients with fibrosis who achieve SVR demonstrate an improvement in necroinflammatory activity and fibrosis regression.[128 –130] Furthermore, the 5-year survival of SVR patients is similar to that of the overall population.[130] The role of interferon in preventing HCC is controversial. A reduced risk of HCC has been noted in patients achieving SVR; however, reports of HCC after SVR was achieved in cirrhotic patients indicate a need for surveillance and reinforce the importance of viral eradication before cirrhosis develops.[131,132] Long-term maintenance therapy with peginterferon does not appear to affect the incidence of HCC.[133]

Davis et al[8] extended their multicohort model to include an assessment of treatment effects, predicting that an increase in the proportion of treated patients (or use of treatment with improved viral clearance rate) would result in reduced rates of cirrhosis, liver failure, HCC, and liver-related death.
Education and Counseling
A lack of knowledge about HCV among health care providers, social service providers, and the public is identified by the IOM as a major challenge to controlling the disease. Education and outreach programs for these audiences feature among the recent IOM recommendations for comprehensive viral hepatitis services aimed at preventing viral transmission, missed diagnosis, and poor health outcomes in HCV.[15]

Increasing access to treatment and providing support to optimize therapeutic adherence might help to improve outcomes. This requires a greater emphasis on early detection along with careful, individualized diagnostic assessment and therapeutic decision-making. Many physicians have adopted a "watch-and-wait" approach, particularly for patients with minimal liver disease. Although this might sometimes be appropriate, patients should be advised of the possibility of unexpectedly rapid disease progression and the need for regular follow-up, including repeat biopsies every 3–5 years. The pros and cons of deferring therapy should be discussed in the context of the patient's clinical and histologic profile.

Many eligible patients decline antiviral treatment. In a study of 280 US patients, 41% declined treatment, citing no symptoms and concerns about side effects.[134] Information provided by health care providers is critical; in 3 US cities, interest in HCV treatment among injection drug users was 7-fold higher among patients who were told that they were at risk for cirrhosis or cancer.[135] Patients under regular review are also more likely to be interested in receiving treatment,[135] emphasizing the importance of communication and continuity of care. Several promising agents, including HCV protease and polymerase inhibitors (eg, telaprevir, boceprevir, and R7128), are in phase 2 or phase 3 trials, with a hope of availability within 2–3 years and beyond.
Changing our Views
The impact of HCV infection on the burden of liver disease is becoming evident as individuals unknowingly infected decades ago age and develop severe sequelae of advanced liver fibrosis. Up to 1 million Americans are predicted to develop HCV-related hepatic complications during the next 2 decades.[26] Persons born between the 1940s and 1960s account for most infections, with the highest risk among those with a history of IDU or blood transfusions before 1992. Once chronic infection is established, disease progression is variable and dependent on several factors. Cirrhosis, liver failure, and HCC might occur at a faster rate and in more patients than previously believed.

HCV infection is a health care priority. Increasing access to treatment might significantly reduce the morbidity and mortality burden of HCV infection.[136] Other measures to tackle the challenge of HCV include improving surveillance, screening and identifying patients at risk of progression, and optimizing therapy. We now need to capitalize on what we know about HCV and formulate strategies to address the anticipated surge in HCV-related morbidity and mortality. New HCV treatments are in development that might increase SVR and potentially decrease the burden of hepatic complications in populations with significant unmet need.

Saturday, November 6, 2010

Hey,I Have Questions About Cirrhosis And My Liver......

Part One: Hey, Can I Get Hepatitis C From.....?
Part Two: Hey, I Have A Question About HCV Tests
Part Four: Answered: Thirty Eight Questions About Hepatitis C

Part Three: Hey, I Have Questions About Cirrhosis And My Liver......

Q-Isn’t it true that the liver can regenerate and does this mean I can get better on my own?
A-Your body can replace old liver cells, called hepatocytes, with new ones. This means that your liver can recover from minor stresses and strains. However, over time damage can cause fibrous scar tissue. This changes the structure of the liver and cannot be repaired. This is why it is so important to spot liver problems before the damage builds up and becomes irreversible.

Q-When does a doctor think liver enzymes readings are cirrhosis?
Wanted to see if anyone knew what liver enzyme reading ast/alt would concern a dr to the point to refer for a biopsy?
A-Doctors don't generally make a diagnosis of cirrhosis based solely on liver enzymes, which are not a reliable indicator of liver damage, i.e. a person can have end-stage liver disease and normal liver enzymes, or a healthy liver and elevated enzymes. While elevated liver enzymes indicate activity going on in the liver, they don't paint the whole picture, nor do they identify a specific liver problem, as many things can account for the elevation. Further, the doctor will also consider: How high are the enzymes? Was it a sudden one-time spike, or have they been up in the 100s over a period of time?

If elevated for a long time, have they remained steady around that level, or have they been steadily increasing? It's important to provide the doctor with a full (honest) history to determine whether there are risk factors for liver disease. Patient history, symptoms, and blood count are among the indicators (as well as enzymes & biopsy) that will help a physician assess liver damage. Liver biopsy remains the "gold standard" of evaluating the liver's condition. However, biopsy isn't always necessary, nor is it always 100% accurate, due to sampling error.

Generally, biopsy is only done to provide additional information that can't be assessed or confirmed through non-invasive measures - information that would help identify a specific liver disease or make a difference in determining a course of treatment. If non-invasive measures do suggest advanced disease (cirrhosis), the doctor may decide against doing a biopsy due to risk. So, in answer to your question, liver disease is complex, and assessing damage isn't as simple as a single test result, i.e. there isn't a liver enzyme level that prompts referral for biopsy, and biopsy isn't always needed to determine that someone has cirrhosis.

Q-Do high liver enzymes indicate serious liver damage?
A-Despite what one might expect, high levels of liver enzymes (transaminases - AST and ALT) in the blood don’t always reveal just how badly the liver is inflamed or damaged. This is an extremely important point to keep in mind. The normal ranges for AST and ALT are around 0 to 40 IU/L and 0 to 45 IU/L respectively. (IU/L stands for international units per liter and is the most commonly accepted way to measure these particular enzymes.) But someone who has an ALT level of 50 IU/L is not necessarily in better condition than someone with an ALT level of 250 IU/L! This is because these blood tests measure inflammation and damage to the liver at an isolated point in time. For instance, if the liver is inflamed on the day that blood was drawn—let’s say if a patient consumes an alcoholic drink a few hours prior to blood being drawn—the levels of the transaminases may be much higher than if the alcohol had not been consumed. Following the same reasoning, if the liver was damaged years before—by excessive alcohol use—the results of a blood test done today may be normal, but a damaged liver may still be present.

Q-What About My Diet ?
A- Cirrhosis refers to the replacement of damaged liver cells by scar tissue. Too much scarring prevents blood flow through the liver. This causes even more damage and loss of liver function. Cirrhosis can hinder the body's use of nutrients and can lead to malnutrition.

Many patients with cirrhosis tend to hold onto (or retain) water. This often is shown first by swelling in the ankles, particularly after walking. The swelling may move up the legs to the abdomen. Water buildup in the abdomen is called "ascites" (pronounced "ah-si-teez").

Sodium (salt)Too much sodium (or salt) in the diet can make the situation worse, because sodium encourages the body to retain water. Your doctor will tell you if you need to limit sodium in your diet. Usually this means restricting sodium intake to about 2,000 mg a day or less.

If you need to restrict sodium, here are some tips that can help:

Avoid salty foods, salt in cooking, and salt at the table. Anything that tastes salty (such as tomato sauce, salsa, soy sauce, canned soups) probably has too much salt. Spice things up with lemon juice or herbs, instead of salt. Fresh foods usually are a better bet than processed foods.

Read food labels when shopping. Check the amount of sodium in the foods you are buying.
Avoid fast-food restaurants. Most fast foods are very high in sodium.

Go easy on meats, especially red meats, which are high in sodium. When possible, consider vegetarian (meat-free) alternatives.

A dietitian can inform you about other products, such as antacids, that also contain lots of sodium.

The more fluid you retain, the greater your need to avoid salt. Your doctor may prescribe diuretics ("water pills") to help you urinate more. But all the water pills in the world won't help if you eat salty foods, such as anchovy pizzas.

Calories and protein
People with cirrhosis may need more extra calories and protein. They may lose their appetite and experience nausea, vomiting, and severe weight loss. This can lead to shortage of the minerals calcium and magnesium (signs include muscle cramps, fatigue, weakness, nausea, and vomiting), or a shortage of zinc (signs include reduced ability to taste, changes in taste).

It can help to eat small, frequent meals (4 to 7 times a day), including an evening snack. Your doctor even may recommend high-nutritional supplement drinks, such as Ensure or Boost.

When the scarring from cirrhosis prevents blood from passing through the liver, pressure increases in the veins entering the liver. This is called portal hypertension. The body is forced to reroute the blood away from the liver and into the general blood circulation. This causes large blood vessels, called "varices," to form.

Because the rerouted blood bypasses the liver, it contains high levels of amino acids, ammonia, and toxins that normally would have been handled by the liver. When these substances reach the brain, they can cause confusion and temporary loss of memory (a condition called "hepatic encephalopathy").

Amino acids and ammonia come from protein in the diet. Some evidence shows that patients with cirrhosis do better when they get their protein from vegetables (such as beans, lentils, and tofu) and from dairy products (eggs, milk, yogurt) instead of from meats.

Doctors can prescribe a syrup called Lactulose to push food through the bowels more quickly. This way, less food is absorbed, the liver has less work to do, and fewer toxins make their way to the brain.

Avoid eating raw oysters or other raw shellfish. Raw shellfish can harbor bacteria (Vibrio vulnificus) that cause severe infections in people with cirrhosis.

Diet For People With Cirrhosis
If your condition has progressed to cirrhosis there are additional considerations you will need to make in your diet to support your liver, learn more here.  For support visit; I Help C - Your Best Friends Guide to Hepatitis C and Cirrhosis

Q-Can antidepressants raise liver enzymes?
A-While SSRIs are considered to be safe for people with liver disease, they can increase liver-related blood tests. However, other causes of liver elevations need to be looked for as the SSRI may or may not be the cause, for example, thyroid disease can also sometimes cause elevations in liver enzymes.

Q-Can prescription medicines, common pharmacy medicines, herbal remedies and illegal drugs affect my liver disease?.
A-Yes. Most drugs (whether prescription, legal or illegal) are processed and broken down by the liver. In people with liver disease where the liver is already under strain, the extra work in breaking down drugs can be dangerous. Make sure all the health professionals (such as your GP, dentist and pharmacist) know about your liver disease before you are given or buy medicines from them. Even common tablets such as aspirin can be dangerous to people with liver problems. Herbal remedies and illegal drugs are a particular risk, as they are not regulated and can contain impurities that cause liver damage. If in doubt, speak to your liver specialist before taking any medicines or drugs.

The following are some tips for managing your medication:

To avoid potentially life-threatening complications, you should talk to your doctor or pharmacist about all medications or supplements - pharmaceutical and herbal - that you are taking or thinking of taking.

Always read the instructions, and never take more than the recommended dose. Taking more than is recommended of any medication could potentially cause harm to the liver.

NEVER mix medication with alcohol. Alcohol only increases the risk of possible liver damage. Acetaminophen can be especially toxic when combined with alcohol.

Consult your doctor about acetaminophen if you have liver disease.

Avoid certain herbal supplements as well as certain vitamins in high doses as they have the potential to cause damage to the liver. Kava, kava kava, comfrey, chaparral, jin bu huan, kombucha tea, pennyroyal, skullcap and shou-wu-pian all may be toxic to the liver.

High doses of vitamins E, K - and especially vitamins A and D - also may be harmful.

Take acetaminophen and all other pain relievers only when really necessary.

Q -What about using Milk Thistle ?
A Laboratory studies suggest that milk thistle may benefit the liver by protecting and promoting the growth of liver cells, fighting oxidation (a chemical process that can damage cells), and inhibiting inflammation. Study results from small clinical trials on milk thistle for liver diseases have been mixed; however, most of these studies have not been rigorously designed, or they have looked at various types of liver diseases—not just hepatitis C. High-quality, well-designed clinical trials have not proven that milk thistle or silymarin is beneficial for treating hepatitis C. The HALT-C study mentioned above found that silymarin use by hepatitis C patients was associated with fewer and milder symptoms of liver disease and somewhat better quality of life, but there was no change in virus activity or liver inflammation

Q-Can I use supplements?
A- In general it is important to keep in mind that excessive doses of iron , vitamin A and niacin have been found to be toxic to the liver. Thus, individuals with liver disease are generally advised to avoid these supplements. And, since osteoporosis ( a disease characterized by reduced bone mass resulting in an increased risk for bone fractures), is common to many liver diseases, it is a good idea for all people with chronic liver disease to take a calcium supplement. Calcium supplementation should be limited to no more than 1000 to 2000 milligrams per day and should be taken with a vitamin D supplement ( which is usually included in the calcium tablet). Since stomach acid is needed to properly absorb calcium, antacids, such as Tums, which reduce stomach acid, are poor sources of calcium. Finally. individuals suffering from ascites- a complication of cirrhosis resulting in an abnormal accumulation of fluid in the abdomen, need to limit their intake of sodium. For every gram of sodium consumed, the accumulation of 200 milliliters of fluid results. The lower the consumption of sodium in the diet, the better controlled this excessive fluid accumulation is. For people with ascites, sodium intake should be restricted to under 1,000 milligrams per day and preferably under 500 milligrams. This goal is difficult, yet attainable.

Iron and Hepatitis C :The liver plays an important role in the metabolism of iron since it is the primary organ in the body that stores this metal. The average American diet contains about 10- 20 mg of iron. Only about 10% of this iron is eliminated from the body. Patients with chronichepatitis C sometimes have difficulty excreting iron from the body. This can result in anoverload of iron in the liver, blood, and other organs. Excess iron can be very damaging to the liver. Studies suggest that high iron levels reduce the response rate of patients with hepatitis C to interferon. Thus, patients with chronic hepatitis C whose serum iron level is elevated, or who have cirrhosis, should avoid taking iron supplementation. In addition, one should restrict the amounts of iron rich foods in their diet, such as red meats, liver, and cereals fortified with iron, and should avoid cooking with iron coated utensils.

Healthcare professionals strongly advised not to take megavitamin therapy or to use nutritional products bought in special stores or by catalogue without consulting your doctor. Some dietary supplements can harm your liver. A few that have caused problems are cascara, chaparral, comfrey, kava, and ephedra.

Learn more by reviewing the following Herbal Glossary available at HCV Advocate: This glossary describes various herbs — the safety concerns, interactions with other medications and potential harms to The goal of the herbal glossary is to help people make an informed decision and stay safe. Note: be sure to inform your medical provider if you are taking any herbs or supplements.

Q-I have cirrhosis what can I take for joint pain ?
A-Acetaminophen is the recommended medication for relieving minor aches, pains, and headaches in people with liver disease. In small doses (less than 4 grams per day, or eight pills taken over a twenty-four hour period of time) acetaminophen is quite safe for the liver—unless combined with alcoholic beverages. (Note: each acetaminophen tablet or pill typically contains 500 milligrams of acetaminophen.) Be careful about mixing Tylenol® with other products that contain acetaminophen. By taking more than one pain reliever at a time, you may accidentally take more acetaminophen than is safe.

Q-What is acetaminophen?
A: Acetaminophen (pronounced: a∙seet·aminofen), is an active ingredient found in many OTC and prescription medicines to help relieve pain and reduce fever.It is also found in combination with other active ingredients, called combination medicines, which treat conditions such as:

symptoms of colds and flu

Medicines containing acetaminophen are available in many forms, including drops, syrups, capsules, and pills. Many people call OTC acetaminophen by a brand name, Tylenol. Others may know Percocet or Vicodin, which are prescription brand names that contain acetaminophen and other active ingredients to help relieve pain.You might see acetaminophen abbreviated as “APAP” on prescription medicines. In other countries, acetaminophen may have a different name. For example, acetaminophen is known as paracetamol in the United Kingdom.

Acetaminophen, supplements and other medications may trigger drug-induced liver injury
November 30, 2016
Download Full Text Article @ AACN Advanced Critical Care
About 46 percent of persons with acute liver failure in the United States have liver damage associated with acetaminophen, making it the most common cause of DILI. Since acetaminophen is often an ingredient in over-the-counter and prescription pain medications, patients may take higher doses than needed.

Liver disease and acetaminophen: can you take it safely?
June 2016
Doctors often tell patients with liver disease that they shouldn't use acetaminophen, a common over-the-counter pain reliever found in Tylenol and many other cold and flu medications. Acetaminophen is broken down by the liver and can form byproducts that are toxic to the liver, so this warning is not completely without merit.

But take it from a hepatologist, acetaminophen is the best option for pain relief for people with liver disease.

Acetaminophen is a “dose-dependent hepatotoxin,” which means that its toxic effects on the liver are related to the amount taken. If anyone takes too much, even those with healthy livers, it will reliably cause an acute injury to the liver. In fact, acetaminophen is the most common cause of acute liver failure in the United States, accounting for almost half of all cases.

The good news is that liver injury can be avoided by limiting the amount of acetaminophen taken each day to 3,000 mg for most people and 2,000 mg for those with chronic liver disease. Staying within these limits will generally prevent liver injury. But the toxic byproducts can accumulate, so it’s best not to take acetaminophen every day.
Continue reading....

Why acetaminophen is the 'most common cause of liver injury' in Canada
Sep 16, 2016
Health Canada's new labelling rules for acetaminophen are not strict enough, and the extra-strength products should be removed from store shelves, some doctors say. Acetaminophen is one of the most widely used pain and fever relievers in Canada and worldwide. It is safe if used properly, but too much can be dangerous, particularly over time.
"It is the most common cause of liver injury. Period. Full stop," said  Dr. Michael Rieder, a pediatric clinical pharmacologist at Western University in London, Ont.

Acetaminophen-induced acute liver injury, acute liver failure occurs more in women
May 23, 2016
​SAN DIEGO —  Despite increased rates of acetaminophen-induced acute liver injury and acute liver failure than male counterparts, women did not experience poorer survival outcomes related to these conditions, according to findings presented at Digestive Disease Week 2016.

AASLD-What Patients Need to Know about Acetaminophen
Hepatitis C Review - Acetaminophen -Tylenol
Q-Can liver cysts cause abdominal pain?
A-Simple liver cysts — fluid-filled cavities in the liver — usually cause no signs or symptoms and need no treatment. However, they may enlarge enough to cause pain or discomfort in the upper right part of the abdomen.

Most liver cysts can be detected on ultrasound or computerized tomography (CT) scans. When needed, treatment may include drainage or removal of the cyst.

The cause of simple liver cysts isn't known, but they may be present at birth (congenital). Rarely, liver cysts may indicate a serious, underlying condition such as:

Polycystic liver disease, an inherited disorder
Echinococcus infection, a parasitic infection
Liver cancer

Q- What is a hemangioma ?
A- Hemangioma (he-man-jee-O-muh) is a noncancerous (benign) mass that occurs in the liver. A liver hemangioma is made up of a tangle of poorly formed blood vessels. Liver hemangioma is sometimes called hepatic hemangioma or cavernous hemangioma.

Most cases of liver hemangioma are discovered during a test or procedure for some other condition. Most people who have a liver hemangioma never experience signs and symptoms and never need treatment.

While it may be unsettling to know you have a mass in your liver, even if it's a benign mass, there's no evidence that an untreated liver hemangioma can lead to liver cancer.

Q-What is the most common benign liver tumors?
A-Hemangiomas are the most common benign tumors of the liver.The name hemangioma derives from the fact that these tumors are filled with heme (blood). They have no malignant potential and may occur in a person with or without underlying liver disease. Hemangiomas occur in the liver in approximately 10 percent of the population, and are usually detected by chance during a sonogram or CT scan performed for the evaluation of an unrelated medical condition. Hemangiomas are more common in women, but can also be found in men, and can occur at any age.

Typically, an individual who harbors a liver hemangioma will not even be aware of it, as these tumors are usually asymptomatic. Some researchers believe that excess estrogen can cause hemangiomas to grow. In fact, growth of hemangiomas has been observed in some women during pregnancy, and in others while taking birth control pills. Furthermore, these people may be at increased risk for rupture. Although the effect of estrogen on hemangiomas is not conclusive, it is advisable for people with hemangiomas to stay off birth control pills and all other forms of estrogen replacement.

In the United States, metastatic tumors are the most common malignancies that occur in the liver. A metastatic liver tumor is a cancer that originally started in an organ other than the liver (known as the primary organ), and then spread to the liver.

Q-Why does my liver hurt ?
A-When diagnosed with hepatitis, patients often expect to feel pain over the liver. And, in fact, many people with chronic hepatitis do experience abdominal pain or discomfort over the liver. Others state that although they do not actually experience pain, they do feel a vague sense of “fullness”, or an “awareness”, of the liver. However, patients who report these symptoms to the doctor, will likely be informed that the liver itself does not typically cause pain or discomfort. Abdominal pain and/or pain over the liver (known as right upper quadrant pain), in people with liver disease may have many causes. This type of pain should not automatically be attributed to a liver disorder – other causes should be investigated. In fact, abdominal and right upper quadrant pain is rarely due to chronic liver disease.Right upper quadrant pain, when due to the liver, occurs most commonly in the acute stages of liver disease, (inflammation of the liver that lasts less than six months), or during a flare - up of a chronic liver disease. In these circumstances, the cause of this pain is due to acute inflammation, irritation, and distention of the liver’s surface. Otherwise, the liver is rarely tender.

Gallstones often occur in individuals with liver disease, especially those with cirrhosis. Other risk factors for gallstones include female gender, obesity, a family history of gallstones, multiple pregnancies, rapid weight loss, and biliary tract narrowing (known as biliary strictures). The typical pain from gallstones is a right upper quadrant discomfort that usually lasts from a half hour to six hours before abating. Pain is usually severe and usually recurs. This pain often radiates to the shoulder or back, and is usually accompanied by nausea and vomiting. Diagnosis of gallstones is typically made by obtaining an abdominal sonogram.Liver cancer may also cause abdominal or right upper quadrant pain. People with a history of chronic hepatitis B or C, and those with cirrhosis due to any chronic liver disease are at risk for developing liver cancer, (also known as hepatocellular carcinoma, (HCC) or hepatoma).

HCC is one of the most common cancers in the world, with its greatest frequency occurring in Asia and Africa. Although its rate of occurrence has been rising over the past twenty years in the United States, it is still uncommon, accounting for only 0.5 to 2 percent of all cancers. The cause of this rise has been linked to the prevalence of chronic hepatitis C in the United States.

Stomach disorders, such as peptic ulcer disease (PUD) and gastritis (inflammation of the stomach lining) often cause abdominal pain in people with liver disease. An upper endoscopy (a procedure wherein a flexible tube with a light at the end is inserted down the esophagus into the stomach and first part of the small intestine) is typically performed in order to diagnose these stomach disorders. During an upper endoscopy, a biopsy is usually taken of the lining of the stomach for Helicobacter pylori, a bacteria which may cause gastritis and ulcers. These stomach ailments are readily treatable with medications known as proton-pump inhibitors, such as Prevacid, Nexium, Protonix or Aciphex, either alone, or in combination with antibiotics, depending upon the precise diagnosis.

Other causes of abdominal and right upper quadrant pain which should be investigated in people with liver disease, include inflammation of the pancreas a condition known as pancreatitis, which may occur with increased frequency in those who drink excessive alcohol, and scar tissue from prior abdominal surgery known as adhesions.

If one experiences abdominal pain along with distention and swelling of the abdomen, ascites must be considered as a cause. Ascites is characterized by accumulation of fluid in the peritoneal cavity – the space between the abdominal organs and the skin, and is the most common complication of cirrhosis. When this is accompanied by a fever and severe abdominal pain, an infection of this fluid should be suspected. This is a serious medical condition known as spontaneous bacterial peritonitis (SBP), and requires immediate hospitalization and treatment.

However, abdominal distention and pain occurring in patients with liver disease may be due to less serious ailments than ascites. For example, abdominal distention and discomfort can result when the digestive tract fills with gas. When this happens, one may experience the sensation of being bloated. This type of abdominal distention may be due to impaired or inadequate absorption known as malabsorption or digestion, known as maldigestion, of certain foods which can be associated with certain liver disorders. This is a controllable condition, and may be treated by the avoidance of specific foods, for example milk-products or wheat (gluten) products

Q- Why does my spleen hurt?
A- Spleen is an important organ of the lymphatic system. It is found on the left upper side of the abdomen, between the 9th and 12th rib. The primary function of the spleen is to produce lymphocytes and plasma cells, which are used in humoral and cellular immune defense. Approximately half of the body’s monocytes are stored in this organ. These cells can easily transform into macrophages and dendritic cells, and assist in wound repair. Additionally, the spleen filters the blood and removes all the unwanted materials like cell debris and microorganisms as bacteria, viruses and fungi.

Furthermore, it monitors the red blood cells, eliminating those that are abnormal, damaged or too old to function properly. It also serves as a storehouse for various elements of the blood like platelets and white blood cells. In the absence of the spleen, the body becomes susceptible to diseases caused by bacteria and protozoa, and responsiveness to certain vaccines also decreases.

Whenever the normal functioning of the body is hampered by disorders like cancer, anemia, malaria, tuberculosis, amyloidosis, cirrhosis, hepatitis and the like, the spleen becomes hyperactive, and starts entrapping and storing a large number of blood cells and platelets. As the result, the platelet and blood cell count in the bloodstream begins to fall dramatically. Due to entrapment, the spleen grows in size, and as it grows, it traps in more and more blood cells and platelets. Eventually the overgrown spleen starts capturing and destroying the normal blood cells together with the abnormal ones. These blood cells and platelets clog the spleen and interfere with its normal function.

The characteristic symptom of spleen enlargement is severe pain in the abdomen and back. At times, the pain shoots up to the left shoulder. This happens when certain parts of the spleen begin to bleed and die due to inadequate supply of blood. The enlarged spleen also starts pressing the stomach, which leads to the feeling of fullness after eating a small amount of food or even without eating anything. Furthermore, as too many blood cells and platelets have been removed from the bloodstream, the body’s immune response begins to dwindle, symptoms of anemia emerge, and normal blood clotting process is also slows down.

In this era of personalized medicine, it is necessary to stratify different risk groups among patients with cirrhosis. As recently proposed, a revised staging of cirrhosis should start with its main classification of compensated and decompensated cirrhosis, 2 separate entities with different prognostic significance. Decompensated cirrhosis is defined by the presence of complications that are mostly secondary to portal hypertension: Ascites, variceal hemorrhage, and/or hepatic encephalopathy....

Q-What is cirrhosis ?
A-Cirrhosis is a description of the extent of scarring of the liver. With cirrhosis, scarring or fibrosis has advanced to the extent that the structure of the liver is altered: the usual smooth texture of the liver starts to become nodular and lumpy. Nodules are areas of liver cells that have become cut off from the rest of the liver by circular bands of scarring with liver cells unsuccessfully trying to regenerate inside the bands. The free flow of blood throughout the liver starts to be compromised.

Q-What are some symptoms of early cirrhosis?
A-Many people with cirrhosis have no symptoms in the early stages of the disease. However, as the disease progresses, a person may experience the following symptoms:

loss of appetite
weight loss
abdominal pain and bloating when fluid accumulates in the abdomen
spiderlike blood vessels on the skin

Q- What is compensated cirrhosis ?
A-Compensated cirrhosis means that the liver is still able to cope with or compensate for the damage and carry out most (sometimes all) of its functions. Cirrhosis, as with fibrosis, ranges from mild (at the beginning) to moderate and severe. Severe cirrhosis can then progress to decompensated cirrhosis.

** For people with Hepatitis C it is important to remember the disease progression is not linear; that is, the process speeds up so it is critical for people to take the necessary steps to make sure that they are receiving the appropriate medical care, which may include HCV therapy to help slow down or stop the disease progression process.

Q-What is decompensated cirrhosis ?
A- Decompensated cirrhosis means that the liver is extensively scarred and unable to function properly. People with decompensated cirrhosis eventually develop many symptoms and complications that can be life threatening.

Q- When does the liver stop working ?
A-The liver can still function with up to 80 percent deterioration. According to the Hepatitis C Trust, 80 to 90 percent of the liver becomes permanently damaged before decompensated occurs.

Q-Can a person have ascities and not have decompensated cirrhosis?
A- While the presence of ascites usually stems from decompensated cirrhosis, there are other causes of ascites, unrelated to liver disease - such as kidney failure, heart failure or ovarian cancer. Veno-occlusive disease can also cause ascites in people who do not have decompensated cirrhosis. In this disease, the hepatic vein becomes clogged, blocking off the blood supply to the liver resulting in ascites. The pyrrolizidine alkaloids which are ingredients of some herbal teas, such as Comfrey tea have been associated with veno-occlusive disorder. Many herbal preparations that contain a mixture of herbs include comfrey, but due to the lack of labeling regulations of herbal products, comfrey may or may not be listed as an ingredient on these products.

Q-Why is my urine a dark color ?
A-Brown urine can be a danger sign of liver disease, according to the University of Maryland Medical Center. Jaundice is often the first sign of liver disease, causing dark urine and yellowed eyes and skin. Cirrhosis, hepatitis, pancreatic cancer, pancreatitis, bile duct cancer and alcoholic liver disease all cause dark urine. Other symptoms of liver disease include an enlarged abdomen, disorientation, easy bruising or bleeding, nausea, loss of appetite and fatigue. Liver disease is a life-threatening disorder.

Q- What happens as liver function decreases?
A-As liver function decreases, fewer proteins such as albumin are produced resulting in fluid accumulation in the legs (edema) or abdomen (ascites). Individuals with cirrhosis may bleed and bruise easily due to a decrease in proteins required for blood clotting. Some people may even experience intense itching due to products that are deposited in the skin.

Q-What problems are associated with the later stages of cirrhosis, or in decompensated cirrhosis?
A-Complications can include:

• Hardening of the Liver due to dying liver cells can be felt on examination.
• As liver disease progresses there is bone mass and density loss.
• A damaged liver is unable to regulate the production and breakdown of some female and male hormones. In women this can cause menstrual irregularities, and in men, gynecomastia (breast enlargement).
• Impaired Mental Status is due to many factors. Toxic substances that are usually filtered by the liver reach the brain. Symptoms of encephalopathy include personality changes, changes in sleep patterns, sluggish movements, drowsiness, confusion, stupor, and coma.
• Itching (pruritus) can develop that can be debilitating. The cause of pruritus is believed to be caused by impairment or failure of bile flow complicated by jaundice.
• Kidney function deteriorates in someone with decompensated cirrhosis, contributing to fluid retention(ascites, edema) and various kidney disorders.
• People with hepatitis C who develop cirrhosis are at risk for liver cancer.
• Muscle wasting can result from the liver’s inability to metabolize proteins, which can make a person with cirrhosis more prone to bone fractures.
• A combination of factors such as portal hypertension,low albumin levels and kidney dysfunction produce an accumulation of fluid in the body. Ascites is the accumulation of fluid in the abdominal cavity. Edema is the accumulation of fluid in the extremities, especially the feet and legs
• Bleeding problems (coagulopathy) develop as the liver
• The spleen stores red and white blood cells and platelets. An enlarged spleen develops due to blood being forced into it when portal hypertension develops. An enlarged spleen loses its ability to store red and white blood cells, and platelets.
• Scar tissue in the liver restricts the flow of blood and leads to portal hypertension resulting in complications such as ascites, spontaneous bacterial peritonitis, varices and other potentially life-threatening complications.
• Spontaneous Bacterial Peritonitis is a condition caused when the body’s natural bacteria enters the ascites fluid causing severe infection.
• The veins in the stomach, esophagus and rectum become so stretched and dilated (due to portal hypertension) that a condition called varices develops which can lead to internal bleeding.

Q-What is hepatic encephalopathy?
A-Hepatic encephalopathy (HE) is a disorder of mental activity, neuromuscular function and consciousness that occurs as a result of either chronic or acute liver failure. This complex neuropsychiatric syndrome is primarily caused by metabolic abnormalities. The syndrome may occur spontaneously or be induced by some precipitating factor and may be reversible, either by improvement in liver function, correction of the precipitating factors or the administration of therapy. However, HE can eventually lead to coma and especially in acute liver failure, may be fatal.

Q-What are the different types of hepatic encephalopathy?
A-Acute or subacute encephalopathy - is generally rapidly progressive over the short course and is a complication of acute liver disease. This type of HE most often occurs in patients with acute fulminant viral hepatitis, toxic hepatitis and Reye's syndrome and is a sign of terminal liver failure.

Acute or subacute recurrent encephalopathy - more than one episode of HE in a patient with chronic disease with cirrhosis, with periods in between without any observable HE.

Specific precipitating factors can usually be identified in association with the recurrent episodes. Even though coma may develop, it is rarely fatal. Chronic recurrent encephalopathy - multiple recurrences of observable HE, requiring continuous therapy to decrease or prevent the development of symptoms during intervening periods.

Usually this type of HE is found in patients who are cirrhotic with an extensive portal collateral circulation with shunts either surgical or spontaneously evolving.

Chronic permanent encephalopathy or myelopathy - permanent neurological abnormalities unresponsive to therapy and forming part of the spectrum of acquired hepatocerebral degeneration and may include a myelopathy. This condition is very rare.

Q-What are the symptoms of hepatic encephalopathy?
A-There are four different stages of symptoms that can occur. The abnormalities that reflect mental and personality changes are distinguished from those reflecting neuromuscular functions.

In Stage 1, the symptoms include mild confusion, short attention span, nightmares and poor night time sleep with daytime sleepiness, restlessness, depression, aimless wandering, anxiety and irritability.
In Stage 2, the mental and personality changes include obvious drowsiness, obvious personality change, gross impairment of ability to do mental tasks, slow response, disobedience, sullenness and disorientation for time and place.
In Stage 3, the symptoms include bizarre behavior, occasional fits of rage, confusion, speech that is incomprehensible, paranoia and anger.
In Stage 4, coma is either responsive or unresponsive.

Q-How is hepatic encephalopathy diagnosed?
A-The diagnosis of HE is made primarily by recognition of neuropsychiatric changes occurring in a patient with known liver disease. In a patient with cirrhosis, whose liver disease has been followed for some time, the diagnosis becomes readily apparent with development of several of the symptoms mentioned above. When confronted with a patient who presents with an encephalopathy or a patient known to have a history of previous or current liver disease and who has neurological impairment, it is very important that attention should be paid to neurological symptoms such as personality changes, hypersomnia, reversal of sleep pattern, presence of precipitating factors such as gastrointestinal bleeding, use of sedative hypnotic drugs, etc. The presence of a flapping tremor is also an important physical finding in a patient with HE. There is no specific diagnostic test, improvement with treatment is the usual method of diagnosis.

Q-What is the treatment for hepatic encephalopathy?
A-The most important aspect of management is the prompt recognition and correction of precipitating factors, when possible. These factors include kidney failure, use of sedatives or narcotics, GI bleeding, hypokalemia/alkalosis, dietary protein increase, infection, constipation and exacerbation of liver disease. The importance of recognizing and correcting any precipitating factors in patients with HE cannot be overemphasized. Every patient with alcoholic cirrhosis and presumed HE should receive thiamine upon admission to hospital.

Additional therapeutic measures include dietary protein restriction and lactulose and occasionally additional neomycin or metronidazole therapy. The use of L-Dopa or bromocriptine is reserved for patients who do not respond to more conventional therapies, even though, in general, these two therapies are not effective in most patients.

Patients with chronic encephalopathy are encouraged to eat vegetable rather than animal protein. Branched-chain amino acid (BCAA) therapy, administered either orally or intravenously, remains the most controversial treatment. Available data about BCAA are conflicting and do not support its routine use. Newer therapies include lactilol, a disaccharide compound quite similar to lactulose. It is reported to be as effective as lactulose or neomycin but is associated with a decreased incidence of severe diarrhea and other side effects. In many patients with chronic liver disease, liver transplantation entirely reverses HE. Thus, liver transplantation may be considered in some patients with hepatic encephalopathy.

Q-What treatments are used to fight liver cirrhosis?
A-Treatments of cirrhosis are aimed at stopping or delaying the disease progress, minimizing liver cell damage and reducing complications. When cirrhosis is caused by alcohol, the patient must stop drinking to halt the progression of the disease. Cirrhosis caused by viral hepatitis may be treated with antiviral drugs to reduce liver cell injury. Medications can be given to control the symptoms of cirrhosis. For example, drugs called "diuretics" are used to remove excess fluid and to prevent edema and ascites from recurring. Combined diet and drug therapy can improve altered mental function. For instance, decreasing dietary protein results in less toxin formation in the digestive tract. Laxatives, such as lactulose, may be given to help absorb toxins and speed their removal from the intestines. A serious consequence of cirrhosis may be bleeding as a result of portal hypertension. Medications, such as beta blockers, may be prescribed to reduce portal hypertension.

Even when complications develop, they can usually be treated. If the patient bleeds from the varices of the stomach or esophagus, the doctor can inject these veins with a sclerosing (hardening) agent administered through a flexible tube (endoscope) that is inserted through the mouth and esophagus. Rubber bands can also be placed around the veins through the endoscope. In critical cases, a liver transplant or a portacaval shunt, which relieves the pressure in the portal vein and varices, may be necessary.

Q-What are varices?
A-Normally, blood from the intestines and spleen is brought to the liver through the portal vein. In people with severe liver damage (cirrhosis) however, the normal flow of blood through the liver is blocked. This can lead to swelling of the liver and potentially the spleen. Blood from the intestines is then rerouted around the liver through small vessels primarily in the stomach and esophagus. Some of these blood vessels become quite large and swollen (varices). These varices may rupture due to high blood pressure (portal hypertension) and thin vessel walls, causing bleeding in the upper stomach or esophagus.

Q-What is a portal systemic shunt?
A-In cases where severe bleeding occurs, surgical shunt procedures may be used to improve the flow of blood through the varices and to stop bleeding and relieve pressure in these swollen blood vessels.

Introduced in 1945, the portal shunt (portal systemic shunt) was the first definitive form of therapy used for patients who had bled from varices. The procedure involves the surgical joining of two veins, the portal vein and the inferior vena cava, to relieve pressure in the portal vein that carries blood into the liver.

Q-Who qualifies for this procedure?
A-Elective portal shunt surgery is performed in only a relatively small number of patients who bleed from esophageal varices. About one-fourth have severe, uncontrollable bleeding requiring emergency surgery.

Q-Is the portal systemic shunt still performed?
A-The shunt operation virtually eliminated recurrent bleeding from varices but its use declined in the 1970's for two major reasons. One was the frequency of encephalopathy (dysfunction of the brain) as a complication. The other was the failure of controlled clinical trials to establish a statistically significant advantage in survival for patients treated with shunts, over those treated with nonsurgical therapy. The failure of portal shunts to enhance survival, reflected the associated complications of encephalopathy and post shunt failure.

Q-What is a distal splenorenal shunt (DSRS)?
A-This operation was devised to preserve the flow of blood through the portal vein to the liver, while decompressing varices in the stomach and esophagus by joining the splenic vein to the left kidney vein. Studies comparing portal systematic shunts with DSRS, found similar rates of overall mortality and cumulative survival. DSRS had a higher operative mortality but a lower rate of encephalopathy afterwards. Also, patients with alcoholic cirrhosis do poorly with DSRS compared to nonalcoholic cirrhotic patients.

Q-What is endoscopic therapy?
A-Endoscopic therapy is a way of reducing variceal bleeding without surgery. In one procedure called endoscopic sclerotherapy, a flexible endoscope is used to inject diluted mixtures of sclerosing (hardening) solutions into the esophageal varices. Another technique called variceal banding, involves placing rubber bands around the veins through the endoscope.

What are the relative advantages and disadvantages of endoscopic therapy over surgical shunts?

The major merit of endoscopic therapy is that it is relatively easy to apply and can be administered at many primary care hospitals. It is commonly used in the initial management of patients with cirrhosis and variceal bleeding. However, patients experiencing gastric (stomach) variceal bleeding, hypertensive gastritis bleeding or repeated esophageal variceal bleeding following endoscopic therapy, should be treated surgically. In this combination, initial endoscopic therapy and selective shunt surgery may significantly improve survival in patients with variceal bleeding.

Q-What is a transjugular intrahepatic portal-systemic shunt (TIPS)?
A-An important recent advance has been the development of the transjugular intrahepatic portal-systemic shunt (TIPS). TIPS is performed by radiologists using only a local anesthetic and a sedative. A long needle is inserted via the jugular vein in the neck, advanced into a hepatic vein and then into a large branch of the portal vein in the liver. Using an inflatable balloon-tipped catheter tube, the section between the portal vein branch and the hepatic vein is widened and then kept open (stented) with a cylindrical wire-mesh stent.

Q-What are the advantages and disadvantages of TIPS?
A-The major advantages of TIPS are that it dispenses with the need for a general anesthetic and a major surgical procedure, both of which are often poorly tolerated by patients with cirrhosis. Another advantage of TIPS is that it reduces ascites (accumulation of fluid in the abdomen) while the DSRS does not. It has been used successfully to treat severe ascites that no longer respond to the use of drugs (diuretic) to reduce the amount of fluid. TIPS is a valuable innovation but it is not without its hazards. Although the direct mortality from TIPS complications is relatively low (less than 5%), this is true only in the hands of experienced radiologists in specialized centres. Approximately one quarter of patients develop encephalopathy after TIPS and these shunts frequently narrow or block up, requiring additional interventional procedures. In the setting of life-threatening bleeding that cannot be controlled by endoscopic therapy, TIPS is probably the ideal shunt procedure if it is readily available. In patients with portal hypertension who have failed treatment with endoscopic therapy and are candidates for liver transplantation in the near future, TIPS is not the preferred type of shunt. The presence of a surgical shunt makes transplant surgery more difficult and may therefore result in an increased risk of complications following liver transplantation. In patients who have recurrent bleeding in spite of endoscopic therapy and whose liver function is good, DSRS may be preferable in the elective or non-emergency setting. Appropriate clinical comparisons between TIPS, DSRS and endoscopic therapy are not yet available and will help to further clarify the place of TIPS in the management of variceal bleeding.

Q-What is ascites and what causes it?
A-When fluid accumulates in the abdominal cavity, it is called ascites. Cirrhosis of the liver is the most common cause of ascites but other conditions such as heart failure, kidney failure, infection or cancer can also cause ascites.

Q-How common is ascites in people with cirrhosis?
A-Ascites is common in people with cirrhosis and it usually develops when the liver is starting to fail. In general, the development of ascites indicates evidence of advanced liver disease and patients should be referred for consideration of liver transplantation.

Q-What causes ascites in patients with cirrhosis?
A-Ascites is caused by a combination of elevated pressure in the veins running through the liver (portal hypertension) and a decrease in liver function caused by scarring of the liver.

Q-What are the symptoms of ascites?
A-Most patients who develop ascites notice abdominal distension and rapid weight gain. Some people also develop swelling of ankles and shortness of breath.

Q-How is ascites diagnosed?
A-Depending on how much fluid is present in the abdomen, ascites may be diagnosed by your doctor on physical examination but is usually confirmed by tests such as ultrasound or CT scan of the abdomen. In the majority of patients, your doctor will recommend that a small needle be inserted through the abdominal wall (after local anesthesia) to remove fluid to be examined in the laboratory. This test is called a paracentesis. The fluid removed will be examined for signs of infection or cancer and to determine the cause for the fluid accumulation.

Q-Is ascites a dangerous sign?
A-Yes. The development of ascites generally suggests that the liver is not working well. The survival rate 5 years after ascites develops is only 30-40% and it is important that you and your doctor discuss a referral to a liver specialist and a liver transplant center.

Q-What are the complications of ascites?
A-Abdominal pain, discomfort and difficulty breathing: These may occur when too much fluid accumulates in the abdominal cavity. This may limit your ability to eat, ambulate and perform activities of daily living.

Infection: This is called spontaneous bacterial peritonitis (SBP) and it usually causes abdominal pain, tenderness, fever or nausea. If this is not promptly diagnosed or treated, a patient may develop kidney failure, severe infection in the blood stream or mental confusion. The diagnosis is generally made by taking a sample of the fluid from your abdominal cavity as described above. This infection can be treated with intravenous antibiotics, and after recovery, patients will require long term treatment with antibiotics to prevent SBP from recurring.

Ascites related hernias: Elevated intra-abdominal pressure can lead to the development of umbilical (around the bellybutton) and inguinal (groin) hernias that can cause abdominal discomfort. Surgical repair is generally avoided unless there is severe pain suggesting the intestines or tissue may be pinched or twisted along with a persistent bulge from the hernia. Surgeons who have experience in treating patients with cirrhosis should perform the operation.

Fluid may get into the chest: This is called hepatic hydrothorax and abdominal fluid fills your lung cavities (mostly on your right side).

Q-How best to treat ascites?
A-The most important step to treat ascites is to strictly reduce your salt intake. Your doctor may advise you to limit your salt intake to 4-5 grams per day (2,000 mg of sodium) or less. As it can be difficult to determine the salt content of various foods, it is generally recommended that a patient with ascites see a nutritionist (dietician) for advice about various foods to avoid. Patients may use salt substitute but it is essential to choose one without potassium because the potassium levels can increase with certain medications to treat ascites. It is important to discuss with your doctor or the dietician which salt substitute you are planning to use.

Most often, patients will require water pills (diuretics) to treat ascites. Your doctor will choose appropriate doses of water pills such as spironolactone (Aldactone) and/or furosemide (Lasix). As these water pills can cause problems with your electrolytes (levels of sodium, potassium, chloride, and bicarbonate in the blood stream), your doctor will need to monitor your blood levels closely. It is important to realize that taking water pills is not a substitute for reducing your salt intake, as water pills will work only when they are taken together with restricted salt intake.

Checking your body weight daily on a scale and contacting your physician whenever there is a gain of more than 10 lbs (or greater than 2 lbs per day for 3 consecutive days) is a good strategy for better management of ascites.

When fluid accumulation cannot be treated optimally with water pills and salt restricted diet, patients may require a large amount of fluid be removed (paracentesis) for relief of symptoms. Your doctors may also discuss with you other procedures such as having a radiologist place a shunt within the liver (called TIPS) to prevent significant fluid accumulation from ascites. As mentioned, patients with ascites have a serious health risk and are often evaluated for liver transplantation.