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

Thursday, March 7, 2019

Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients

Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients
Lybeck, Charlottea; Brenndörfer, Erwin D.c; Sällberg, Mattic; Montgomery, Scott M.b,d,g; Aleman, Sooe,f; Duberg, Ann-Sofia

SVR is associated with clinical cure and regression of liver fibrosis in most patients after 10 years of FU. However, occult HCV infection can be detected in some patients many years after achievement of SVR; this may have a negative effect on the regression of liver fibrosis, but more studies are needed. Future studies are planned to determine whether the viable virus can be recovered from PBMC. If so, this raises the question of whether those repetitively positive for HCV in PBMC should be retreated. Further, the risk of HCC is not eliminated in all noncirrhotic patients with SVR. Studies of the long-term outcome more than 10 years after IFN therapy and eventually after DAA therapy are needed.

Full-text available online...

Objectives Curing of hepatitis C virus (HCV) infection primarily aims to prevent severe liver complications. Our objectives were to investigate the long-term presence and impact of occult HCV infection (OCI) and to study the outcomes in terms of liver disease after virological cure.

Patients and methods A total of 97 patients with achieved sustained virological response (SVR) during 1990–2005 were followed either by a clinical follow-up (FU) visit with blood sampling and liver elastography (n=54) or through national registries for outcomes (n=43). To diagnose OCI among patients with SVR, a highly sensitive method was used to detect HCV-RNA traces in whole blood. The FU duration was a median of 10.5 years, with samples up to 21.5 years after the end of treatment (EOT).

Results The majority of patients [52 (96%)] were HCV-RNA negative at FU, and regression of fibrosis was statistically significant. OCI was found in two (4%) of them at 8 and 9 years after EOT. These patients had F1 and F2 fibrosis before treatment and F2 at FU, but no other abnormal findings. Three previously noncirrhotic men were diagnosed with hepatocellular carcinoma 8–11 years after EOT.

Conclusion Occult infection could be detected many years after the achievement of SVR but was not associated with serious liver disease. The majority had persistent viral eradication and regression of fibrosis after SVR. However, an increased risk of hepatocellular carcinoma may persist in the long term after SVR even in noncirrhotic patients. Further studies with FU after direct-acting antiviral therapy and on the long-term impact after cure are needed.
Continue reading...….

European Journal of Gastroenterology & Hepatology: April 2019 - Volume 31 - Issue 4 - p 506–513 doi: 10.1097/MEG.0000000000001316 Original Articles: Hepatology

On This Blog
Read All Posts With The Label Liver Cancer
Review a collection of current research articles extracted from peer-reviewed journals, liver meetings/conferences, and learning activities investigating the natural history of liver cancer, approved therapies, risk factors associated with chronic viral hepatitis, cancer-prevention, including diet, nutrition and physical activity, and trends associated with the rising rate of hepatocellular carcinoma in the U.S.
Begin, here.....

Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase? Research is saying no, check out an index of articles here..... 

Saturday, March 2, 2019

Current and future pharmacological therapies for managing cirrhosis and its complications

World J Gastroenterol. Feb 28, 2019; 25(8): 888-908
Published online Feb 28, 2019. doi: 10.3748/wjg.v25.i8.888

Current and future pharmacological therapies for managing cirrhosis and its complications
David Kockerling, Rooshi Nathwani, Roberta Forlano, Pinelopi Manousou, Benjamin H Mullish, Ameet Dhar 

Core tip: Pharmacological therapy is central to the management of cirrhosis and its complications. Whilst there has been recent debate about the safety of beta-blockade in patients with ascites, conversely there is growing interest in potential benefits relating to a reduction in gut bacterial translocation and hepatocellular carcinoma risk. In addition to its well-established role in treating hepatic encephalopathy, rifaximin may also have a key role in preventing secondary infections. In this review, we summarise these and other uncertainties, controversies and novel developments related to pharmacotherapy in the clinical management of chronic liver disease.

View full-text article online: 

Saturday, February 23, 2019

Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases—meta‐analytic assessment

Cancer Med. 2019 Feb 21. doi: 10.1002/cam4.1998. [Epub ahead of print]
Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases-meta-analytic assessment.
Tarao K1, Nozaki A2, Ikeda T3, Sato A4, Komatsu H5, Komatsu T6, Taguri M7, Tanaka K8.

Abstract BACKGROUND:
It is well known that the incidence of developing hepatocelluler carcinoma (HCC) is increased in liver cirrhosis of different etiologies. However, comparison of HCC incidence in various liver diseases has not yet been estimated. We surveyed this comparison.

METHODS: The PubMed database was examined (1989-2017) for studies published in English language regarding the prospective follow-up results for the development of HCC in various liver diseases. A meta-analysis was performed for each liver disease.

RESULTS: The annual incidence (%) of HCC in the non-cirrhotic stage and cirrhotic stage, and the ratio of HCC incidence in the cirrhotic stage/non-cirrhotic stage were as follows. (a) hepatitis B virus liver disease: 0.37%→3.23% (8.73-fold), (b) hepatitis C virus liver diseases: 0.68%→4.81% (7.07-fold), (c) primary biliary cholangitis (0.26%→1.79%, 6.88-fold), (d) autoimmune hepatitis (0.19%→0.53%, 2.79-fold), and (e) NASH (0.03%→1.35%, 45.00-fold). Regarding primary hemochromatosis and alcoholic liver diseases, only follow-up studies in the cirrhotic stage were presented, 1.20% and 2.06%, respectively.

CONCLUSIONS: When the liver diseases advance to cirrhosis, the incidence of HCC is markedly increased. The development of HCC must be closely monitored by ultrasonography, magnetic resonance imaging, and computed tomography, irrespective of the different kinds of liver diseases.

DISCUSSION
--Download Full-text--
It is known that cirrhosis is present in 80~90% of HCC patients with any underlying liver disease,119 and it is the most important risk factor for HCC. However, comparison of the incidence of HCC in various liver diseases was not accurately and precisely evaluated in previous studies. In this study, we found that the incidence of HCC is highest in HCV LC (4.81%/year) and second highest in HBV LC (3.23%), followed by alcoholic LC (2.06%), PBC LC (1.79%), NASH LC (1.35%), primary hemochromatosis (1.20%), and AIH (0.53%).
        
The incidence of HCC has been wildly studied in patients with HBV LC and HCV LC, and was reported to be 3% and 5%,29, 120 which was almost the same as that in our study.

In this study, we also demonstrated that the incidence of HCC is markedly increased (2.79‐ to 45.00‐fold) in the cirrhotic state compared with non‐cirrhotic state, irrespective of the etiology of liver disease. Why this increase in HCC development occurs in the cirrhotic state must be considered.

First, chronic inflammation may be a key mechanism for HCC development in the cirrhotic state. In this respect, we made clinical observation in the HCV LC patients (Child A) in the past. The LC patients were divided into three groups: Group A: 28 patients whose annual average serum alanine aminotransferase (ALT) level was persistently high (≧80 IU; high‐ALT group); Group B: 28 patients whose annual average serum ALT levels was persistently low (<80 IU; low‐ALT group), and Group C: 13 unclassified patients. The patients had been followed up prospectively. The 5‐year incidence rate of HCC in the high‐ALT group was as high as 53.6% compared with only 7.1% in the low‐ALT group (P < 0.001).120 Thus, this clinical observation demonstrated the importance of chronic inflammation in the development of HCC in HCV LC.
        
The same tendency was demonstrated in HBV LC. Chen et al121 reported that high serum levels of HBV DNA and ALT were independent risk factors for HCC development in HBV infection. Ishikawa et al20 also reported that serum aminotransferase are one of predictive factor for the development of HCC. One important mechanism for high incidence of HCC in HCV LC and HBV LC as compared with the incidence of HCC in LC caused by other etiologies may be the sustained high‐grade inflammation.
        
Furthermore, in autoimmune hepatitis, persistent elevation of serum aminotransaminase was reported to lead to the development of HCC.78 This suggests a role for inflammation in the development of HCC, but this hypothesis has not been confirmed solidly.
         
Second, increases in DNA synthesis in the hepatocytes of cirrhotic patients is suspected as a possible mechanism of HCC development. In our previous study, we demonstrated that in the high DNA synthetic group [BrdU (thymidine analog) labeling index ≧1.5%] 64.3% of patients developed HCC in 5 years, in contrast to 14.3% in the low DNA synthesis (Brd U LI <1.5%) group in HCV LC patients (P < 0.05).122 We further demonstrated that in HCV‐associated cirrhosis patients who showed nodular formation on ultrasound, the cell cycle of hepatocytes was markedly accelerated, as estimated by the bromodeoxyuridine (thymidine analog) uptake into hepatocytes in vitro, and the incidence of HCC was greatly increased.123

Third, accumulated genomic change was also important factor for HCC development. In this respect, Hiatt et al124 reported that C282Y mutation itself may increase the risk of HCC development in hereditary hemochromatosis. In addition, in alcoholic LC, the genetic effect of long‐term alcoholic intake may influence the development of HCC.125

Fourth, obesity, and diabetes are suspected to increase the incidence of developing HCC. In a large epidemiologic study, patients with BMI >35 had an increased risk of cancer, especially HCC, with hazard ratio (HR) of 4.52.126 In addition, diabetes is associated with HCC occurrence, with a HR of 2.39 in a US cohort.127 It is generally accepted that NASH is associated with obesity and diabetes in high percentages.

Notably, in 2014, Flemming et al128 predicted the risk of HCC in patients with cirrhosis, using the ADRESS‐HCC risk model. They examined the l‐year probability of HCC in various liver diseases in 34 932 patients in the national transplantation waitlist database. HCC developed in 1960 patients (5.6%) during a median follow‐up of 1.3 years. Six baseline clinical variables including age, diabetes, race, etiology of cirrhosis, sex, and severity (ADRESS) of liver dysfunction were independently associated with HCC. They settled ADRESS‐HCC risk model from these data and the risk model well‐coincided with the clinical observation. They concluded that the risk model was clinically useful tool for predicting the risk of HCC in patients with diverse etiologies.

In addition, the aging of the patients must be taken into the consideration, as the cirrhotic patients were considered to be older than the non‐cirrhotic patients in almost all liver diseases. In this regard, Asahina et al129 investigated the difference of HCC incidence in aging in HCV‐associated liver disease, and found that the incidence of HCC was higher in the older patients (>65 years old) than the younger patients (<65 years old). The same tendency was observed by Taura et al130 However, the difference in incidence was approximately twofold. So, it is difficult to explain the marked difference in HCC incidence between the cirrhotic state and non‐cirrhotic state found in this meta‐analysis. Regarding other liver diseases, there were very few reports which demonstrated a difference between patients in the non‐cirrhotic and cirrhotic states concerning age.

The next consideration is the prevention of patients not to become cirrhosis state. We demonstrated that the incidence of HCC in the cirrhotic state and that in the non‐cirrhotic state were markedly different in many liver diseases; therefore, efforts to prevent patients with liver diseases from progressing to the cirrhotic state by all means is very important.

In HBV infection, the effort to diminish HBV‐DNA by pegylated interferon (Peg IFN)19 or oral antiviral agents, such as entecavir (ETV), tenofovir, and tenofovir anafenamide, is important. Indeed, ETV and tenofovir were reported to prevent the occurrence of HCC.131, 132In HCV infection, Peg IFN plus ribavirin or direct‐acting antivirals (DAAs) are effective to eliminate HCV, and may be prevent the progression of the disease, resulting in prevention of HCC development.

In primary biliary cholangitis, administration of ursodeoxycholic acid is important. Indeed, the risk of HCC in UDCA‐treated PBC patients was reported to be relatively low.59, 63

In autoimmune hepatitis, well‐designed corticosteroid therapy is important to prevent HCC development, and persistent elevation of serum aminotransaminase is reported to lead the development of HCC.78 It seems that alleviation of serum ALT levels might prevent HCC development, but this hypothesis is not confirmed solidly.
        
In NASH patients, improvement in metabolic syndrome, especially improvement in diabetes mellitus and obesity, is important.

Next, we mentioned whether the treatment of underlying liver diseases substantially modulates the HCC risk or not. We restricted the survey chiefly to the cirrhotic patients because they are at high risk of HCC development.

Continue to full-text article:
https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.1998

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

KEYWORDS: hepatocellular carcinoma; liver cirrhosis; liver diseases; meta-analysis; risk of HCC

Tuesday, February 19, 2019

Understanding Liver Disease with Dr. Joe Galati

In this timeless patient-friendly video, Dr. Joe Galati will explain medical jargon used to describe common and possible severe symptoms of liver disease, relaunched this month by Liver Specialists of Texas, located in Houston.

Topics
Varices
Encephalopathy - Video
Ascites
Peritonitis infection of ascitic fluid
Fever
Abdominal Pain
Shortness of breath
Chest Pain
Headache
Jaundice
Liver transplant evaluation



Links
View additional videos on Dr. Galati's YouTube Channel, connect on Facebook, follow on twitter, or visit both his blog and website.

Wednesday, February 13, 2019

Cirrhosis: What Clinicians Need to Know

Cirrhosis: What Clinicians Need to Know
Listen to Christine Kerr, MD, AAHIVS, of Hudson River HealthCare, discuss specific challenges in managing cirrhosis in an easy to access webinar using a case-based patient scenario, provided by HepCure.

Although; Cirrhosis: What Clinicians Need to Know, is intended for physicians and health care professionals, anyone, especially patients will benefit from watching the presentation.


Learning Objectives
1. Describe cirrhosis.
2. Discuss screening guidelines and diagnostic algorithms for cirrhosis.
3. Review cirrhosis treatment best practices.
Begin here....

View All Presentations At HepCure
Webinar Archive 

Christine Kerr, MD, AAHIVS, is the medical director for the HIV and Hepatitis Programs for Hudson River HealthCare. She trained in internal medicine at Brown University and Infectious Disease at Harvard. She is the community co-chair for the New York State Hepatitis C Elimination Task force, the co-chair of the NYS AIDS institute Quality Advisory committee and is co-chair for the NYS AIDS Institute/Johns Hopkins Guidelines Committee for Treatment of Hepatitis C in the Primary Care Setting. Her areas of interest include treatment of HIV and Hepatitis C in the community setting, care of the underserved, and program development and evaluation.

Monday, February 11, 2019

Gilead Data On Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

Media
A fatty liver drug from Gilead Sciences posts negative results in late-stage clinical trial
By Adam Feuerstein @adamfeuerstein
February 11, 2019
Gilead Sciences said Monday that its experimental drug, called selonsertib, failed to improve liver scarring compared to a placebo in a Phase 3 clinical trial. The study enrolled nearly 900 patients with compensated cirrhosis, an advanced form of NASH at higher risk for liver-related death.
Read it here...

In The Journals 
What is Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis

Press release
Gilead Announces Topline Data From Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced that STELLAR-4, a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib, an investigational, once-daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), in patients with compensated cirrhosis (F4) due to nonalcoholic steatohepatitis (NASH), did not meet the pre-specified week 48 primary endpoint of a ≥ 1-stage histologic improvement in fibrosis without worsening of NASH.

In the study of 877 enrolled patients who received study drug, 14.4 percent of patients treated with selonsertib 18 mg (p=0.56 vs. placebo) and 12.5 percent of patients treated with selonsertib 6 mg (p=1.00) achieved a ≥ 1-stage improvement in fibrosis according to the NASH Clinical Research Network (CRN) classification without worsening of NASH after 48 weeks of treatment, compared with 12.8 percent of patients who received placebo. Selonsertib was generally well-tolerated and safety results were consistent with prior studies.

“While we are disappointed that the STELLAR-4 study did not achieve its primary endpoint, we remain committed to advancing therapies for patients with advanced fibrosis due to NASH, where there is a significant unmet need for effective and well-tolerated treatments. Gilead has a long-term commitment and proven track record of addressing significant challenges in the field of liver diseases. Data from this large study of patients with compensated cirrhosis due to NASH, including the extensive set of biomarkers collected, will further advance our understanding of the disease and inform our broader NASH development programs,” said John McHutchison, AO, MD, Chief Scientific Officer, Head of Research and Development, Gilead. “We are grateful to the patients and investigators who participated in the STELLAR-4 study, and we now await the upcoming results from the Phase 3 STELLAR-3 trial of selonsertib in patients with bridging fibrosis (F3) due to NASH and the Phase 2 ATLAS combination trial of selonsertib, cilofexor (GS-9674) and firsocostat (GS-0976) in patients with advanced fibrosis due to NASH later this year.”

Further in-depth analysis of the findings is ongoing and the data will be submitted to an upcoming scientific conference. Gilead will work with the Data Monitoring Committee and investigators to conclude the STELLAR-4 study in a manner consistent with the best interests of each patient.

Selonsertib, cilofexor and firsocostat, alone or in combination, are investigational compounds and are not approved by the U.S. Food & Drug Administration (FDA) or any other regulatory authority. Safety and efficacy have not been established for these agents.

About Selonsertib and the STELLAR-4 Study
Selonsertib is an investigational small molecule inhibitor of ASK1, a protein that promotes inflammation, apoptosis (cell death) and fibrosis in settings of oxidative stress. Oxidative stress can be increased in many pathological conditions including liver diseases such as NASH.

The STELLAR-4 study is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with compensated cirrhosis (F4) due to NASH. Eligible adults ages 18 to 70 years were randomized and received selonsertib 18 mg (n=354), selonsertib 6 mg (n=351) or placebo (n=172) for up to 240 weeks. Either selonsertib or placebo is being administered orally once daily. The primary endpoints of the study are a composite of the proportion of patients who achieve a ≥ 1-stage improvement in fibrosis according to the NASH CRN classification without worsening of NASH at week 48 and event-free survival at week 240 as assessed by time to the first clinical event. Further information about the clinical study can be found at www.clinicaltrials.gov.

About Gilead’s Clinical Programs in NASH
NASH is a chronic and progressive liver disease characterized by fat accumulation and inflammation in the liver, which can lead to scarring, or fibrosis, that impairs liver function. Individuals with advanced fibrosis, including bridging fibrosis (F3) or compensated cirrhosis (F4), are at a significantly higher risk of liver-related mortality and all-cause mortality.
Gilead is advancing multiple novel investigational compounds for the treatment of advanced fibrosis due to NASH, evaluating single-agent and combination therapy approaches against the core pathways associated with NASH – hepatocyte lipotoxicity, inflammation and fibrosis. Investigational compounds in development include the ASK1 inhibitor selonsertib, the selective, non-steroidal FXR agonist cilofexor (GS-9674) and the ACC inhibitor firsocostat (GS-0976). The STELLAR-3 Phase 3 trial evaluating selonsertib among NASH patients with bridging fibrosis (F3) is ongoing. Cilofexor and firsocostat are currently in Phase 2 studies in NASH, including the ATLAS Phase 2 trial evaluating combinations of selonsertib, cilofexor and firsocostat in advanced fibrosis (F3 and F4) due to NASH.

About Gilead Sciences
Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California. For more information on Gilead Sciences, please visit the company’s website at www.gilead.com.

Monday, February 4, 2019

Hepatocellular carcinoma in non-cirrhotic liver: A comprehensive review.

World J Hepatol. 2019 Jan 27;11(1):1-18. doi: 10.4254/wjh.v11.i1.1.

Hepatocellular carcinoma in non-cirrhotic liver: A comprehensive review.
Desai A1, Sandhu S2, Lai JP3, Sandhu DS4.

Full-text Article

Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which in turns accounts for the sixth most common cancer worldwide. Despite being the 6th most common cancer it is the second leading cause of cancer related deaths. HCC typically arises in the background of cirrhosis, however, about 20% of cases can develop in a non-cirrhotic liver. This particular subgroup of HCC generally presents at an advanced stage as surveillance is not performed in a non-cirrhotic liver. HCC in non-cirrhotic patients is clinically silent in its early stages because of lack of symptoms and surveillance imaging; and higher hepatic reserve in this population. Interestingly, F3 fibrosis in non-alcoholic fatty liver disease, hepatitis B virus and hepatitis C virus infections are associated with high risk of developing HCC. Even though considerable progress has been made in the management of this entity, there is a dire need for implementation of surveillance strategies in the patient population at risk, to decrease the disease burden at presentation and improve the prognosis of these patients. This comprehensive review details the epidemiology, risk factors, clinical features, diagnosis and management of HCC in non-cirrhotic patients and provides future directions for research.

Thursday, January 17, 2019

After The Cure: What’s Next? Hepatitis C Post-Treatment Management

Listen to experts discuss important HCV related topics in the following easy to access webinar series provided by HepCure.

Achieved SVR, What’s Next? HCV Post-Treatment Management
This month Dr. Anthony Martinez of University at Buffalo presented; Achieved SVR, What’s Next? HCV Post-Treatment Management. 

Topics Discussed
1. Define sustained virologic response (SVR).
2. Describe how to manage cirrhotic patients post-SVR
3. Discuss at-risk populations for HCV reinfection

Begin here.....

View All Presentations

Recommended Reading 
AASLD-IDSA Hepatitis C Guidance:
Monitoring Patients Who Are Starting HCV Treatment, Are on Treatment, or Have Completed Therapy
Post-Treatment Follow-Up for Patients Who Achieved a Sustained Virologic Response
Patients who have undetectable HCV RNA in the serum, as assessed by a sensitive polymerase chain reaction (PCR) assay, ≥12 weeks after treatment completion are deemed to have achieved SVR. In these patients, HCV-related liver injury stops, although they remain at risk for non-HCV–related liver disease, such as fatty liver disease or alcoholic liver disease. Patients with cirrhosis or advanced fibrosis remain at risk for developing hepatocellular carcinoma (HCC).
Continue reading...….

May 2017 Gastroenterology
American Gastroenterological Association Institute Clinical Practice Update—Expert Review: Care of Patients Who Have Achieved a Sustained Virologic Response After Antiviral Therapy for Chronic Hepatitis C Infection
Ira M. Jacobson, Joseph K. Lim, Michael W. Fried

Full-text - Download PDF

Background and Objective
With the advent of safe and highly effective DAAs, cure of HCV infection has become more frequent. On the basis of randomized and observational studies, systematic reviews, and expert opinion, the authors of this clinical practice update present key recommendations about whether, when, and how long HCV patients who have achieved SVR should receive ongoing liver care.

Key Points
Confirm long-term virologic response at 48 weeks posttreatment. This recommendation is based on clinical trial results that have identified a late-relapse rate of ±0.5%. However, further confirmation of virologic response beyond 48 weeks posttreatment is not supported by the available evidence.

For patients with stage 3 fibrosis or liver cirrhosis, continue post-SVR surveillance for hepatocellular carcinoma (HCC) for an indefinite period of time, since research has identified no point beyond which the risk for HCC is reduced to that of patients without liver disease. For patients with earlier stages of fibrosis, no surveillance is recommended.

Continue endoscopic screening for varices in all patients with cirrhosis (whether or not they have SVR). However, in patients with SVR who are not at risk for progressive liver disease, if no varices are identified within 2 to 3 years, cessation of further surveillance may be considered.

Noninvasive methods can be used to assess progression and regression of fibrosis after SVR. However, do not alter HCC surveillance protocols in patients with baseline cirrhosis, even when regression of fibrosis is noted, since fibrosis regression assessed by noninvasive testing has not been shown to accurately indicate a reduction in HCC risk.


Tuesday, January 1, 2019

Editorial: Long-awaited treatment for hepatitis C virus decompensated cirrhosis

Journal of Gastroenterology
pp 1–2 |
Long-awaited treatment for hepatitis C virus decompensated cirrhosis
Kiminori Kimura

Editorial
First Online: 01 January 2019
Organ fibrosis is pathologically progressive due to the abnormal accumulation of extracellular matrix occurring during the wound healing process of repeated injuries and necrosis associated with inflammation and tissue necrosis [1]. It also causes organ dysfunction, reportedly accounting approximately 30% of the cause of death in developed countries [2]. Therefore, development of therapeutic drugs against fibrosis is an urgent problem. Liver cirrhosis, also known as liver fibrosis, is caused by viral hepatitis such as hepatitis B virus (HBV) and hepatitis C virus (HCV) and fatty liver, which are recently increasing and alcohol consumption. HCV cirrhosis, accounting for the majority of domestic liver cirrhosis, progresses from compensated Child–Pugh (CP) classification A with comparatively hepatic reserve preservation to decompensated CP-B and CP-C. As the liver cirrhosis progresses, complications such as ascites, jaundice, and encephalopathy increasingly occurred due to decreased liver function and ruptured esophageal varices, because of portal hypertension, which affect the prognosis of patients with cirrhosis. In fact, the one-year CP-C survival rate is approximately 40% [3]. In addition, cirrhosis is the primary cause of liver cancer that ranked as the fifth cause of domestic death; therefore, therapeutic drugs should be developed.

With the breakthrough advent of direct-acting antivirals (DAAs) against HCV, most patients infected with HCV could be excluded [4]. With the development of this therapeutic agent, several reports have demonstrated that antiviral therapy for chronic hepatitis and compensated cirrhosis, which improves liver function and prevents the occurrence of liver cancer, becomes possible [5, 6, 7]. Reports from domestic clinical trials as well as overseas treatment results have indicated good sustained virologic response (SVR) 12 results after DAA administration [8, 9, 10]. Since DAAs had fewer side effects compared with the conventional treatment based on IFN, subjects who were contraindicated with IFN (those with thrombocytopenia, leukopenia, depression, and kidney disorder, among others) can now be treated, which will greatly decrease the number of patients infected with HCV. Under these circumstances, patients with decompensated cirrhosis who are contraindicated with DAA still remain in the treatment target group. In Europe and the United States, liver transplant has been established as the standard treatment option, but remains not very popular in Japan. In one reported case, a sofosbuvir + ledipasvir + ribavirin combination therapy for decompensated cirrhosis achieved SVR12 and improved liver function, but there are no therapeutic medicines approved in Japan at present [11]. Therefore, decompensated cirrhosis remains one of the unmet medical needs in Japan.

In a study published in this issue, Takehara et al. demonstrate that administration of sofosbuvir + velpatasvir ± ribavirin combination therapy against HCV decompensated cirrhosis is sufficiently safe and effective [12]. Regardless of ribavirin involvement, the SVR 12 is 92%, which is comparable to that of the previous reports from other Western countries [13]. This therapeutic agent seems effective for HCV genotype 1 or 2, which is common in Japan. Compared with ASTRAL-4, a previous trial on concomitant administration of sofosbuvir + velpatasvir ± ribavirin for decompensated cirrhosis, this study’s subjects could tolerate, although they were older than the registered patients (aged 66 vs. 58 years). Although this study reports that cirrhosis worsened in the ribavirin combination group, these patients should be carefully monitored because of the increasing death cases.

One of the notable results of this report is that if patients with decompensated cirrhosis can achieve SVR 12, approximately 25% of them showed improvement from CP-B to CP-A even in a short period of time. This is an effect of improved protein synthesis ability, such as of albumin. These results can improve the prognosis of decompensated cirrhosis by eliminating the causative HCV despite progression to decompensated cirrhosis. Future studies should also be conducted to confirm this finding; however, we expect that these DAAs will have a similar effect as IFN treatment, and may also reduce the incidence of liver cancer.

Finally, we need to consider which type of patients with decompensated cirrhosis should be treated in the future. In Japan, where liver transplantation is not actively carried out, the purpose of extending the period until the transplantation is not applicable, and analyzing the cost-effectiveness based on treatment is required. In addition, using DAAs eliminates the causative factors of liver cirrhosis, which will only recover normally due to the liver’s regenerative ability. It has been demonstrated that resolution of cirrhosis takes time after HCV eradication [14]; therefore, therapeutic drugs that dissolve fibrosis are desirable in the future. 

Friday, November 30, 2018

Combination interventions for Hepatitis C and Cirrhosis reduction among people who inject drugs: An agent-based, networked population simulation experiment

Combination interventions for Hepatitis C and Cirrhosis reduction among people who inject drugs: An agent-based, networked population simulation experiment
Bilal Khan, Ian Duncan, Mohamad Saad, Daniel Schaefer, Ashly Jordan, Daniel Smith, Alan eaigus,
Don Des Jarlais, Holly Hagan, Kirk Dombrowski 

Published: November 29, 2018



Fig 1. Finite state diagram of the HCV model used in the experiments.
Once infected, agents face a series of stochastic and enforced progressions through a series of ever worsening liver function. Throughout the simulation, infected agents who have reached a chronic state (non-acute HCV infected agents) face a small but regular chance of moving directly to cirrhosis, decompensated cirrhosis, or hepatocellular carcinoma. In addition, their Metavir fibrosis level is incremented yearly, moving them gradually from early stage fibrosis to cirrhosis. Once in any of the three severe liver stages, agents face an increasing probability of death due to HCV infection, incremented on a five year basis.
https://doi.org/10.1371/journal.pone.0206356.g001

Full-text article:

Abstract
Hepatitis C virus (HCV) infection is endemic in people who inject drugs (PWID), with prevalence estimates above 60% for PWID in the United States. Previous modeling studies suggest that direct acting antiviral (DAA) treatment can lower overall prevalence in this population, but treatment is often delayed until the onset of advanced liver disease (fibrosis stage 3 or later) due to cost. Lower cost interventions featuring syringe access (SA) and medically assisted treatment (MAT) have shown mixed results in lowering HCV rates below current levels. However. little is known about the potential cumulative effects of combining DAA and MAT treatment. While simulation experiments can reveal likely long-term effects, most prior simulations have been performed on closed populations of model agents—a scenario quite different from the open, mobile populations known to most health agencies. This paper uses data from the Centers for Disease Control’s National HIV Behavioral Surveillance project, IDU round 3, collected in New York City in 2012 to parameterize simulations of open populations. To test the effect of combining DAA treatment with SA/MAT participation, multiple, scaled implementations of the two intervention strategies were simulated. Our results show that, in an open population, SA/MAT by itself has only small effects on HCV prevalence, while DAA treatment by itself can lower both HCV and HCV-related advanced liver disease prevalence. More importantly, the simulation experiments suggest that combinations of the two strategies can, when implemented together and at sufficient levels, dramatically reduce HCV incidence. We conclude that adopting SA/MAT implementations alongside DAA interventions can play a critical role in reducing the long-term consequences of ongoing HCV infection.

Perinatal Exposure to HCV Leads to Earlier Cirrhosis

Recommended Reading
Liver Meeting 2018 
Sofosbuvir/ledipasvir cures most young children with hepatitis C
Liz Highleyman / 13 November 2018
Almost all young children ages 3 to 6 years with chronic hepatitis C achieved sustained virological response after 12 weeks of treatment using sofosbuvir/ledipasvir oral granules, according to findings presented at the ..

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Full-text article downloaded & shared via twitter by Henry E. Chang:

Perinatal Exposure to HCV Leads to Earlier Cirrhosis
Samantha DiGrande
A recent retrospective review of patients who contracted hepatitis C (HCV) in childhood found that those with perinatal infection developed cirrhosis earlier than other risk groups.

A recent retrospective review of patients who contracted hepatitis C (HCV) in childhood found that those with perinatal infection developed cirrhosis earlier than those in other risk groups.
Read more:
https://www.ajmc.com/newsroom/perinatal-exposure-to-hcv-leads-to-earlier-cirrhosis

Abstract
Modin L, Arshad A, Wilkes B, et al. Epidemiology and natural history of hepatitis C virus infection among children and young people [published online November 26, 2018]. J Hepatol. doi: 10.1016/j.jhep.2018.11.013.

Highlights
• HCV infection in UK children - IV drug use 53%; blood products 24%; perinatal 11%
• Cirrhosis in 32% of patients at median of 33 years irrespective of infection route.
• Treatment impact on disease progression better if started before cirrhosis.
• Anti-HCV therapy should be available in childhood to prevent long-term liver disease.
Read more:
https://www.journal-of-hepatology.eu/article/S0168-8278(18)32545-5/fulltext

Thursday, November 29, 2018

Ribavirin Beneficial For Patients with Hepatitis C Genotype 3

Ribavirin Beneficial For Patients with Hepatitis C Genotype 3
NOVEMBER 29, 2018
Kenneth Bender, PharmD, MA

The addition of ribavirin to a regimen of sofosbuvir and velpatasvir (Epclusa) to treat hepatitis C virus (HCV) genotype 3 appeared to increase efficacy for patients with compensated cirrhosis, particularly in those with resistance-associated substitution (RAS), in a trial that sought to confirm the therapeutic strategy for this considered difficult-to-cure population.

Rafael Esteban, MD, of the Vall d'Hebron Hospital University, Spain, and colleagues conducted the comparison in patients with compensated cirrhosis to elaborate on earlier indications of ribavirin benefit from phase 2 studies, and from the ASTRA-4 study in patients with HCV genotype 3 and decompensated cirrhosis.
Read more:
https://www.mdmag.com/medical-news/ribavirin-beneficial-for-patients-with-hepatitis-c-genotype-3

Recommended Reading
The Liver Meeting
San Francisco
November 2018

On This Blog
Review research articles with a focus on treating HCV according to genotype using FDA approved  medicines. Information is extracted from news articles, peer-reviewed journals, as well as liver meetings/conferences, research manuscripts and interactive learning activities.

Thursday, November 22, 2018

Blogging About Liver Disease: Reasons To Be Grateful


Happy Thanksgiving! This year, and every year, I am grateful for a small group of talented bloggers who continue to keep us informed about all types of viral hepatitis.

In the spirit of the holiday, each blog has featured many reasons to be thankful this year; from curing HCV to improving the treatment of HIV.

Latest Articles 
Some of the following blogs are published by support organizations, healthcare professionals or physicians, while others are written from a patients perspective, offering us healthy tips about each stage of liver disease.

New @ HIV and ID Observations
Paul E. Sax, MD
As noted here before, I’m a big fan of Thanksgiving, a great excuse to get together with family and friends, and to eat a gargantuan amount of food.*

Hepatitis B Foundation
Holidays with Hepatitis B: How to Tell Your Family
hepbtalk
As the holidays approach, families are planning parties and dinners and preparing to spend time with their loved ones. In such a merry atmosphere, the idea of discussing hepatitis B – whether its a recent diagnosis or the first time that you are ready to disclose your status – may be intimidating. However, it doesn’t have to be! In honor of National Family Health History Day – which falls on Thanksgiving – we put together some tips to help you start the conversation.

Joseph Galati, M.D.
Tips for a Healthier Holiday
Ahh, the holidays. A time to celebrate all the good that has come our way during the previous year. First up: Thanksgiving. What better way to begin the year-end wrap-up than to sit down at a hearty meal with family and friends? But the holidays are arguably the toughest time of the year to eat..

Hep Blogs
Finding Gratitude in Sickness, Health and Hepatitis 
By Lucinda K. Porter, RN
Some good news in the hepatitis C realm, plus a look at the practice of gratitude.

Mavyret versus Epclusa
By Greg Jefferys
Both Mavyret and Epclusa give cure rates above 97% for all genotypes of Hepatitis C except for G3 where both give a cure rate of around 95%.

The End Times
By Grace Campbell
Who gave cirrhosis such a catchy generic title? End stage liver disease. There’s a name sure to invoke confidence.

Liver Meeting 2018 Wrap-Up: Vaccines, Diet, and an Increasing Liver Menace 
By Lucinda K. Porter, RN
Ending the week with summaries of research from the 2018 Liver Meeting. I cover hepatitis B vaccination, diet and alcoholic liver disease.

HepatitisC.net
Options for Treatment with Liver Cancer
By Karen Hoyt
After my diagnosis of liver cancer, I had to find out what options for treatment were available.

ADRLF (Al D. Rodriguez Liver Foundation)
Who says a fantastically delicious Thanksgiving spread can’t be healthy? This year, make your Thanksgiving feast even more special with these liver-healthy options that won’t give you or your family that post-holiday guilt; nor will they keep you stuck in the kitchen for hours on end! Check out these appetizing recipes for a healthy, scrumptious, easy-to-prep (or time-saving) Thanksgiving meal!

Finding Hope in Affordable Hepatitis Screening
Screening remains to be the best defense against detecting the hepatitis virus in its earliest stages, and potentially developing life-threatening complications, later down the line. Dubbed as the “silent killer,” hepatitis doesn’t exhibit obvious symptoms in many people, who may live, comfortably, with the virus for years and only discover their condition at its advanced, acute stage. Noting the importance of the timeliness of testing, Texas-based Link2Labs is making affordable hepatitis C tests available to uninsured and underinsured people.

HCV News
Weekly Review
Catch up on what you missed this week, read HepCBC's - Weekly Bull.

FYI - Lettuce Recall 
“I believe it’s all related to a big increase in obesity and type 2 diabetes in this country,” lead study author Zobair M. Younossi, MD, MPH, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases. “Those two risk factors drive NAFLD and its progressive type, nonalcoholic steatohepatitis (NASH). That accounts for at least part of the increase in mortality related to liver disease.”

AGA Journals - Blog
Dr. Kristine Novak
Persistent drinking of very hot coffee can cause exfoliative esophagitis due to thermal injury, researchers report in the November issue of Clinical Gastroenterology and Hepatology. Florian Schertl et al describe the case of a 55-year-old woman with new retrosternal pain upon swallowing. She had been receiving continuous and successful proton pump inhibitor.

Fatty Liver Disease
Canadian Liver Foundation
It Happened To Me | My Fatty Liver Journey
Melanie was all too familiar with fatty liver disease, with her husband being diagnosed 5 years earlier. But, she never thought it would happen to her.

The Flu & You
Canadian Liver Foundation
What’s intended to help shouldn’t hurt
Before you head to the cabinet for medication, there are a few things you should know to ensure that what you take will help, not hurt.

One Medical blog
So you’ve come down with a nasty bug that’s been making the rounds.

This Blog
Flu Activity Updated Nov 10/News Articles Nov 16
Weekend Reading - Baby Boomers and the Flu

Recommended Blogs
Dr Paul Gow talks all things the liver and answers call-in questions on ABC Nightlife 


Source - Hepatitis Victoria

On Twitter
Shared by @HenryEChang 

Just Because
Matthew Kaskavitch
CU Anschutz Medical Campus experts share Thanksgiving health insights
Thanksgiving is almost here, and that means two things: 1) time spent with family and friends around the television watching football, and 2) eating turkey. Lots and lots of turkey. At this time of year, we often overindulge and loosen our belt and wonder how we fit all that stuffing and gravy into our stomach. Don’t worry. We asked leading health experts from the University of Colorado Anschutz Medical Campus a few of the Thanksgiving questions you’ve always wanted to know the answer to.

Happy Thanksgiving!

Tuesday, November 13, 2018

AbbVie's MAVYRET™ (glecaprevir/pibrentasvir) Shows High Virologic Cure* Rates in Treatment-Naïve Hepatitis C Patients with Compensated Cirrhosis

The Liver Meeting® 2018
Meeting Updates 
View all updates on this blog, (LINK), coverage elsewhere, (LINK).
Related Links:
High SVR12 rate for 16 week glecaprevir/pibrentasvir regimen in HCV GT1

Today's Press Release
AbbVie's MAVYRET™ (glecaprevir/pibrentasvir) Shows High Virologic Cure* Rates in Treatment-Naïve Hepatitis C Patients with Compensated Cirrhosis

- EXPEDITION-8 is the first Phase 3b study evaluating 8 weeks of MAVYRET™ in treatment-naïve chronic hepatitis C virus (HCV)-infected patients with compensated cirrhosis across all major genotypes (GT1-6)[1] 

- In cohort one, 100 percent of genotype 1, 2, 4, 5 and 6 treatment-naïve chronic HCV patients with compensated cirrhosis achieved SVR[12] with 8 weeks of MAVYRET per protocol analysis[1]
- Cohort two of the study is ongoing, evaluating treatment-naïve genotype 3 (GT3) patients with compensated cirrhosis 

- MAVYRET is currently approved as an 8-week, pan-genotypic treatment for treatment-naïve patients without cirrhosis

NORTH CHICAGO, Ill., Nov. 13, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new data for its pan-genotypic chronic hepatitis C virus (HCV) treatment, MAVYRET™ (glecaprevir/pibrentasvir), in treatment-naïve patients with compensated cirrhosis. Results from the Phase 3b EXPEDITION-8 study showed that with 8 weeks of MAVYRET, 100 percent (n=273/273) of genotype 1, 2, 4, 5 and 6 patients achieved a sustained virologic response 12 weeks after treatment (SVR12) per protocol analysis.1

These data are being presented today as a late-breaking, oral presentation at The Liver Meeting® 2018 organized by the American Association for the Study of Liver Diseases (AASLD) in San Francisco, California.

"Current guidelines recommend a 12-week pan-genotypic regimen for people who have hepatitis C, are treatment-naïve and have compensated cirrhosis," said Robert S. Brown, Jr., M.D., the Gladys and Roland Harriman professor of medicine, Weill Cornell Medical College. "We are interested in investigating shorter treatment options, which may simplify care for patients with compensated cirrhosis while providing high cure rates."

This analysis is part of the ongoing Phase 3b EXPEDITION-8 study evaluating the safety and efficacy of MAVYRET in treatment-naïve chronic HCV patients with compensated cirrhosis across all major genotypes (GT1-6).1 The study includes two cohorts; cohort one with genotype 1, 2, 4, 5, 6 chronic HCV-infected patients, and cohort two with genotype 3 (GT3) chronic HCV-infected patients.1

"MAVYRET is already having a significant impact on people living with HCV. However, there are still groups of patients who may benefit from a shorter treatment option," said Janet Hammond, M.D., Ph.D., vice president, infectious diseases development, AbbVie. "We continue to investigate and understand the value of an 8-week treatment regimen for patients, something we recognize as an important step towards HCV elimination."

To date, no virologic failures have been reported in cohort one of the study and no patients have discontinued treatment due to adverse events.1 Adverse events (>5%) reported of the study populations include pruritus (9.6%), fatigue (8.6%), headache (8.2%) and nausea (6.4%).1 Six serious adverse events (2%) have occurred during the study, none of which were deemed to be related to glecaprevir/pibrentasvir.1 No new safety signals were identified in this study.

Data from the ongoing EXPEDITION-8 Phase 3b study will be presented as a late-breaking, oral presentation during the Late-breaking Abstract Oral Session II on November 13 at 8:30 a.m. PST.

MAVYRET is approved in the U.S. as a 12-week pan-genotypic treatment for treatment-naïve patients with compensated cirrhosis.2

*Patients who achieve a sustained virologic response at 12 weeks post treatment (SVR12) are considered cured of hepatitis C.

About the EXPEDITION-8 Study1
EXPEDITION-8 is an ongoing non-randomized, single arm, open-label, multicenter Phase 3b study evaluating the safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve GT1-6 chronic HCV patients with compensated cirrhosis. The study investigated two cohorts of patients:
Cohort one: treatment-naïve genotype 1, 2, 4, 5, 6 patients with compensated cirrhosis (n=280)
Cohort two: treatment-naïve GT3 patients with compensated cirrhosis (n=60)

The primary endpoint is the percentage of patients achieving SVR12 in a per-protocol analysis and the secondary endpoints are on-treatment virologic failure and relapse rates. For cohort one, 280 patients were enrolled and seven patients were excluded from the SVR12 per-protocol analysis (n=273); five patients were lost to follow up, and two patients received less than 8 weeks of treatment (one of these two patients achieved SVR12).

Additional information on the clinical trials for MAVYRET is available at www.clinicaltrials.gov/.

About MAVYRET™ (glecaprevir/pibrentasvir)
MAVYRET™ is approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic hepatitis C virus (HCV) infection in adults across all major genotypes (GT1-6). MAVYRET is a pan-genotypic, once-daily, ribavirin-free treatment that combines glecaprevir (100mg), an NS3/4A protease inhibitor, and pibrentasvir (40mg), an NS5A inhibitor, dosed once-daily as three oral tablets, taken with food.

MAVYRET is an 8-week, pan-genotypic option for patients without cirrhosis and who are new to treatment, who comprise the majority of people living with HCV. MAVYRET is also approved as a treatment for patients with specific treatment challenges, including those (GT1) not cured by prior treatment experience to either a protease inhibitor or NS5A inhibitor (but not both), and in patients with limited treatment options, such as those with severe chronic kidney disease (CKD) or those with genotype 3 chronic HCV. MAVYRET is a pan-genotypic treatment approved for use in patients across all stages of CKD.

Glecaprevir (GLE) was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors.

Full prescribing information can be found here.

Monday, November 12, 2018

High SVR12 rate for 16 week glecaprevir/pibrentasvir regimen in HCV GT1

Combo HCV Pill Effective in Certain Refractory Patients
High SVR12 rate for 16 week glecaprevir/pibrentasvir regimen in HCV GT1 patients
by Molly Walker, Staff Writer, MedPage Today November 11, 2018 
November 11, 2018
A 16-week treatment course had a SVR 12 of 95%, including 94% in non-cirrhotic patients and 97% in cirrhotic patients who had failed prior treatment containing NS5A inhibitors, with no virologic failure among those with HCV genotype 1b infection, reported Mark S. Sulkowski, MD, of Johns Hopkins Hospital in Baltimore.

He said that glecaprevir/pibrentasvir was approved by the FDA in 2017 for treatment of NS5A inhibitor-experienced patients with genotype 1 infection and no NS3/4A protease inhibitor therapy.

A 16-week course of treatment was approved based on a small group of 17 patients in a trial where 16 of 17 achieved SVR12, Sulkowski explained at a press conference at the annual Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD).

But that wasn't enough for the AASLD/Infectious Diseases Society of America (IDSA) guidelines panel, which labeled the therapy an "alternative regimen" and did not put it in the recommended category for treatment for this population, with "concerns based on the small number of human beings treated."
Read More: https://www.medpagetoday.com/meetingcoverage/aasld/76266
Website MedPage Today Twitter @medpagetoday

Coverage > Liver Meeting
Mavyret SVR high in patients with Sovaldi, NS5A inhibitor experience
November 11, 2018
SAN FRANCISCO — Mavyret was highly effective and well-tolerated in patients with chronic hepatitis C genotype 1 who had experience with a combination of Sovaldi, NS5A inhibitor and ribavirin, according to data presented at The Liver Meeting 2018.

“The context of this study was that the FDA granted approval in August 2017 for [Mavyret] for 16 weeks in persons who failed an NS5A-containing regimen that did not also contain a protease inhibitor,” Mark S. Sulkowski, MD, from Johns Hopkins Hospital in Maryland, said during a press conference presentation.
Website Healio - Twitter @HealioHep

Combined Glecaprevir/Pibrentasvir Highly Effective in HCV Patients Who Have Failed Other Therapies 
SAN FRANCISCO – Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found the combination of glecaprevir and pibrentasvir is highly effective and well tolerated in patients with chronic hepatitis C virus (commonly called HCV) genotype-1 infections who have prior treatment experience with sofosbuvir/NS5A inhibitor.

Meeting Updates 
View all updates on this blog, (LINK), coverage elsewhere, (LINK).

Abstract
American Association for the Study of Liver Diseases
Website AASLD Twitter @AASLDtweets

AASLD Poster Roundup: Factors that Impact Cirrhosis Diagnosis

Meeting Coverage > AASLD
AASLD Poster Roundup: Factors that Impact Cirrhosis Diagnosis
Selections from poster sessions at the annual Liver Meeting
Nov 11
by Elizabeth Hlavinka, Staff Writer, MedPage Today
SAN FRANCISCO -- Over 40,000 people die of cirrhosis and chronic liver disease per year, and determining which factors increase the risk of this illness is important for implementing prevention and treatment methods.

This issue was explored in poster presentations at the annual Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD).


Meeting Coverage
Website MedPage Today
Twitter @medpagetoday

Sunday, November 11, 2018

Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

In Case You Missed It

Can J Gastroenterol Hepatol. 2018 Oct 3;2018:6095097. doi: 10.1155/2018/6095097. eCollection 2018.

Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals.
Drazilova S1, Janicko M2, Skladany L3, Kristian P4, Oltman M5, Szantova M6, Krkoska D7, Mazuchova E7, Piesecka L8, Vahalova V8, Rac M9, Schreter I4, Virag L4, Koller T10, Liptakova A11, Ondrasova M12, Jarcuska P2.

This retrospective study confirmed that the prevalence of either type 2 diabetes mellitus ( T2DM ) or impaired fasting glucose (IFG) increases in chronic hepatitis C patients with the degree of fibrosis; patients with F4 fibrosis had 27.1% prevalence of IFG and 31.8% of T2DM. The predictive factors for T2DM had besides F4 fibrosis also higher age and BMI. Significant decrease of fasting glycemia at the end of treatment and 12 weeks after that was observed in the whole cohort and in subgroups of patients with type 2 diabetes mellitus, impaired fasting glucose, Child-Pugh A cirrhotic patients, treatment experienced patients, and treatment experienced cirrhotics. Long term follow-up may further show if the achievement of SVR after DAA treatment will reduce the risk of future T2DM development similarly to SVR after interferon treatment and if the improvement of glycemic control in patients with T2DM decreases the risk of chronic complications and improves survival.

Open Access

Abstract
Background and Aims
Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C.

Methods 
We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals.

Results
We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis.

Conclusion
We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.


30402450 PMCID:
PMC6192081 DOI: 10.1155/2018/6095097

Monday, October 29, 2018

Mavyret (glecaprevir/pibrentasvir) 8 Wks Improved Cardiovascular and Metabolic Outcomes and Stable Renal Function

Infect Dis Ther. 2018 Oct 27. doi: 10.1007/s40121-018-0218-x. [Epub ahead of print]

Pan-Genotypic Hepatitis C Treatment with Glecaprevir and Pibrentasvir for 8 Weeks Resulted in Improved Cardiovascular and Metabolic Outcomes and Stable Renal Function: A Post-Hoc Analysis of Phase 3 Clinical Trials. 
Tran TT1, Mehta D2,3, Mensa F3, Park C3, Bao Y3, Sanchez Gonzalez Y4.

First Online: 27 October 2018

Treatment with Glecaprevir and Pibrentasvir G/P for as short as 8 weeks showed improved glucose and triglyceride levels by post-treatment week 4 irrespective of treatment history and cirrhosis status. These benefits were especially pronounced in patients with elevated triglycerides, pre-diabetes and diabetes at baseline. Treatment with G/P also resulted in stable eGFR function in both during and post-treatment periods. Future studies are needed to determine whether these effects are maintained over longer periods of time.

Full-Text

Abstract
Introduction
Chronic hepatitis C (CHC) infection is associated with extrahepatic manifestations (EHMs) which can affect renal, cardiovascular and other comorbidities. The effect of CHC treatment with short-duration regimens on these EHMs is not well defined. Hence, we examined longitudinal estimated glomerular filtration rate (eGFR), triglycerides and glucose values to assess the impact of short-duration CHC therapy on renal, cardiovascular and metabolic diseases, respectively.

Methods
We conducted analyses of all patients without cirrhosis treated with glecaprevir and pibrentasvir (G/P) for 8 weeks in two phase 3 clinical trials. In addition, one phase 3 trial was carried out to explore the effects of treatment on renal EHMs in patients with advanced renal impairment at baseline. As a sensitivity analysis, we included all CHC patients treated with G/P for 8 or 12 weeks enrolled across five phase 3 trials. Adjusting for baseline demographics and clinical properties via mixed regression models enabled evaluation of changes in EHMs through end of treatment.

Results
G/P treatment for 8 weeks resulted in statistically significant declines in triglycerides (− 28.6 mg/dl) and glucose (− 11.2 mg/dl), while there was no statistically significant decline in eGFR. Biomarker improvements were greatest among patients with elevated triglycerides and elevated glucose at baseline. Similar effects were observed across all patients treated with G/P for 8 or 12 weeks.

Conclusion
Short-duration treatment with G/P resulted in stable renal function and improvements in cardiovascular and metabolic EHM markers, especially in patients with severe EHMs at baseline.

Continue reading: https://link.springer.com/article/10.1007%2Fs40121-018-0218-x

Additional Reading
HCV Advocate
Hepatitis C is NOT just a liver disease-it affects the entire body. Check out our fact sheet that lists some of the more common and uncommon extrahepatic manifestations of hepatitis C.

Navigate this blog 
Sift through current research articles on the extrahepatic manifestations of hepatitis C.

Sunday, October 28, 2018

Long term outcome of antiviral therapy in HBV patients with cirrhosis

World J Gastroenterol. Oct 28, 2018; 24(40): 4606-4614
Published online Oct 28, 2018. doi: 10.3748/wjg.v24.i40.4606
Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis 
Young-Cheol Ju, Dae-Won Jun, Jun Choi, Waqar Khalid Saeed, Hyo-Young Lee, Hyun-Woo Oh 

Full-text Article 
https://www.wjgnet.com/1007-9327/full/v24/i40/4606.htm

Core tip: It is well known that antiviral treatment improves clinical outcomes of chronic hepatitis B-associated decompensated cirrhosis. However, long term and large scale clinical data regarding survival rate, and incidence of hepatocellular carcinoma in patients with decompensated cirrhosis in the antiviral era are lacking. We investigated the survival rate and incidence of hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis by using the Health Insurance Review and Assessment database. Long term outcome of treating hepatitis B-associated decompensated cirrhosis using antiviral agents improved much compare to previous reports. Cumulative mortality rate and incidence of HCC was sharply decreased after one year antiviral treatment.

AIM
To investigate survival rate and incidence of hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis in the antiviral era. 

METHODS
We used the Korean Health Insurance Review and Assessment. Korea’s health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance guidelines. Overall, 48365 antiviral treatment-naïve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1st decompensated chronic hepatitis B (CHB) and treatment-naïve patients (n = 7166). 

RESULTS
The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1st decompensated CHB treatment-naïve subjects. But the annual mortality rates sharply decreased to 3.4% (2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5% (1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-naïve patients was 3.4% (2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-naïve patients. 

CONCLUSION
Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.
Continue reading......

Thursday, October 25, 2018

Curing hepatitis C reduces the risk of cardiovascular events

Liz Highleyman
Published: 25 October 2018
Several studies have found that people with hepatitis C are more prone to developing cardiovascular conditions such as coronary artery disease, peripheral vascular disease, myocardial infarction and stroke; however, other studies have not seen this association.

A growing body of evidence shows that HCV treatment can help reverse this increased risk. A recent study from France, for example, found that curing hepatitis C reduces the risk of cardiovascular events in people with compensated cirrhosis. But again, some large studies from the interferon era did not see a similar benefit. 

On This Blog
A collection of current research articles on ailments related to HCV
Article directory on the extrahepatic manifestations of hepatitis C.

The following study investigated the prevalence of early signs of cardiovascular damage in patients with HCV cirrhosis. Is such damage reversible following treatment with DAAs? 

Full-text article available online @ Medscape, or purchase article, here

A Prospective Study
Aliment Pharmacol Ther. 2018 Oct;48(7):740-749. doi: 10.1111/apt.14934. Epub 2018 Aug 10.

Subclinical cardiovascular damage in patients with HCV cirrhosis before and after treatment with direct antiviral agents: a prospective study.
Novo G1, Macaione F1, Giannitrapani L2, Minissale MG2, Bonomo V1, Indovina F1, Petta S3, Soresi M2, Montalto G2, Novo S1, Craxi A3, Licata A2,3.

Abstract
BACKGROUND:
Cirrhosis is associated with morpho-functional cardiovascular alterations.

AIMS: 
To detect early features of cardiovascular damage in HCV-compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short-term behaviour after HCV eradication with direct antiviral agents (DAAs).

METHODS: 
Thirty-nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain and ultrasound scan of carotid arteries. HCV-cirrhotics were reassessed by echocardiography and carotid ultrasound after obtaining sustained virological response (SVR) on DAAs.

RESULTS: 
HCV-cirrhotics showed at baseline a significantly reduced global longitudinal strain compared to controls -18.1 (16.3-20.5) vs -21.2 (20.4-22.3), P < 0.001. They also had a significantly higher pulse wave velocity 8.6 (7.7-9.1) m/s vs 6.6 (6.0-7.1) m/s, P = 0.0001, and β-stiffness index 12.4 (11.1-13.5) vs 8.6 (8.0-9.2) P = 0.0001. At multiple regression analysis, diabetes and HCV cirrhosis were independent predictors of global longitudinal strain. All HCV-cirrhotic patients had SVR on DAAs. Follow-up available in 32 of 39 (82%) at 9 (8-10) months showed a significant improvement of tricuspid annular plane systolic excursion (P = 0.01) and lateral E' velocity compared to baseline (P = 0.001).

CONCLUSIONS: 
HCV-cirrhotics show a significant rate of subclinical cardiac and vascular abnormalities. At a time when their survival is less linked to progression of liver disease, due to viral eradication on DAAs, cardiovascular morbidity and mortality may take a significant role.
Continue to full-text: https://www.medscape.com/viewarticle/902665
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