Weekend Reading: HCV Extrahepatic Manifestations - Diseases outside of the liver

Weekend Reading: HCV Extrahepatic Manifestations

Greetings from Michigan! Will you be taking time out to enjoy a few holiday festivities this weekend?

The short people and Nana are preparing to visit a man with a red suit, sure hope SC is sitting closer to the food court this year.

HCV Extrahepatic Manifestations
Today's topic is HCV related extrahepatic manifestations; diseases outside of the liver.  

The Bad News
Did you know it's estimated that over 40% of patients with chronic hepatitis C may develop at least one extrahepatic manifestation during the course of their disease?

The Good News
In order not to keep you from your weekend activities - any research highlights have been cut short, and only relevant links to easily digested  information is provided, sort of.

Patient-Friendly Materials: Extrahepatic Manifestations of Hepatitis C
If you fall into the majority of people who don't enjoy reading a bunch of medical jargon, head over to HCV Advocate and review their "Easy C" Series on Extrahepatic Manifestations of Hepatitis C, launched just a few days ago.

Extrahepatic Manifestations (overview)

Cryoglobulinemia
Kidney Disease (MPGN)
Lichen Planus
Non-Hodgkin's Lymphoma (NHL)
Peripheral Neuropathy (PN)
Pictures of Extrahepatic Manifestations
Vasculitis

Hepatitis C-related Extrahepatic Manifestations And Symptoms  

The University of Washington offers a quick overview of; Extrahepatic Conditions Related to Hepatitis C. The following chart lists a range of  hepatitis C-related extrahepatic manifestations and symptoms.  

Symptom/Manifestation and Potential HCV Related Syndrome 

Learn more, here.

Extrahepatic manifestations of chronic hepatitis C virus infection: 297 cases from a tertiary medical center in Beijing, China

Cheng Zhaojing, Zhou Baotong, Shi Xiaochun, Zhang Yao, Zhang Lifan, Chen Limeng and Liu Xiaoqing

For our medical nerds who love data, we begin with a large study found online in the Chinese Medical Journal 2014. The aim of the study was to determine the presence of extrahepatic manifestations in Chinese patients with chronic HCV infection. Medical records of 297 patients (mean age, 55 years; 50.8% men) were reviewed to determine the presence of the following clinical manifestations: fever, fatigue, arthralgia, Raynaud’s phenomenon, palpable purpura, renal impairment, sicca syndrome involving mouth and eyes, thyroid dysfunction, type 2 diabetes mellitus, pulmonary fibrosis, lichen planus, paresthesia, lymphoma, and cancers. Duration of infection was 14.16 years, and approximately 26% of the cohort had HCV for more than 20 years.

According to results extrahepatic manifestations (EMs) were found to be common in Chinese HCV patients, particularly fatigue, type 2 diabetes, renal impairment, lymphadenophy, fever, and thyroid dysfunction. The study found 62% of patients had at least one extrahepatic manifestation (EM), including fatigue (29.4%), diabetes mellitus (28.2%), renal involvement (12.5%), lymphadenopathy (9.6%), fever (9.4%), thyroid dysfunction (8.1%) and arthralgia (7.4%).

Older age was associated with EMs. Also noted by the researchers; Despite the high prevalence of EM, only 36.2% (194/536) patients with anti-HCV positive were seen by a specialist and a few were tested for cryoglobulin. 

Read more about the study, here. 

Hepatitis C Infection Tied to Higher Risk of Death From Non-liver Cancers

Hepatitis C has long been associated with the development of hepatocellular carcinoma, the most common type of liver cancer. In fact, HCV is the leading risk factor for HCC in the United States, and the second leading risk factor for HCC world-wide, but recently a study found people with HCV are at a higher risk for Non-liver cancers as well.

Presented at the annual meeting of the American College of Preventive Medicine this year, Reuters Health reported on; the first U.S. study to investigate and show people with chronic hepatitis C have a higher risk of death from non-Hodgkin lymphoma (NHL).  As expected, the risk of dying from liver cancer was elevated among HCV-infected patients - nearly 30 times higher than among non-infected individuals.

Continue reading....

Cure of HCV infection reduces symptoms and mortality from severe extrahepatic manifestations

AASLD/IDSA/IAS– Guidance for Testing, Managing, and Treating Hepatitis C, offers clinical insight into the benefits of curing HCV. 

SVR is associated with more than 70% reduction in the risk of liver cancer, 90% reduction in the risk of liver-related mortality and reduces symptoms and mortality from severe extrahepatic manifestations.

Excerpt; WHEN AND IN WHOM TO INITIATE HCV THERAPY

Cure of HCV infection also reduces symptoms and mortality from severe extrahepatic manifestations, including cryoglobulinemic vasculitis, a condition affecting 10% to 15% of HCV-infected patients. (Fabrizi, 2013); (Landau, 2010) HCV-infected persons with non-Hodgkin lymphoma and other lymphoproliferative disorders achieve complete or partial remission in up to 75% of cases following successful antiviral therapy for HCV infection. (Gisbert, 2005); (Takahashi, 2012); (Svoboda, 2005); (Mazzaro, 2002); (Hermine, 2002) These reductions in disease severity contribute to dramatic reductions in all-cause mortality. (van der Meer, 2012); (Backus, 2011) Lastly, patients achieving SVR have substantially improved quality of life, which includes physical, emotional, and social health. (Neary, 1999); (Younossi, 2013) Because of the myriad benefits associated with successful HCV treatment, clinicians should treat HCV-infected patients with antiviral therapy with the goal of achieving an SVR, preferably early in the course of their chronic HCV infection before the development of severe liver disease and other complications.

Continue reading here....

Links Of Interest

Index of articles and research: 

Extrahepatic Manifestations Related To Hepatitis C

Research

HCV Extrahepatic Mortality-kidney/heart/cancers
Extrahepatic Manifestations of Hepatitis C Virus

Remember to exercise your mind on the weekends, your body during the week and your sense of humor daily.

Tina

Vox performs a checkup on Sovaldi

Vox performs a checkup on Sovaldi

Sarah Kliff delivers a much-needed piece on the $1,000 pill
By Trudy Lieberman

Score one for Vox.com! The website’s article earlier this week about the costly hepatitis C drug Sovaldi is one I’ve been waiting for since the drug debuted a year ago with its $84,000 price tag and boosterish press coverage. Vox health policy reporter Sarah Kliff knits together the strands of the drug’s journey from development to clinical success to shock at its high price tag and debate over its use and its impact on the healthcare system. She sums up:

Sovaldi is an instructive study in how the American healthcare system allows drugs to become expensive—an incredible, unprecedented, and $1,000-per-pill type of expensive that the country has never seen before. The story of Sovaldi shows the American healthcare system is incapable of fighting back against these prices. 

Continue reading 

Fighting an Uphill Battle': Experience With the HCV Triple Therapy

Fighting an Uphill Battle': Experience With the HCV Triple Therapy
What support is needed for patients undergoing the burdensome HCV triple therapy?

BMC Infectious Diseases

Available @ Medscape:

Fighting an Uphill Battle': Experience With the HCV Triple Therapy
Qualitative Thematic Analysis
Manuela Rasi, Patrizia Künzler-Heule, Patrick Schmid, David Semela, Philip Bruggmann, Jan Fehr, Susi Saxer, Dunja NiccaDisclosures

BMC Infect Dis. 2014;14(507)
December 05, 2014 

Discussion Provided Below

View Full Text:

• Abstract and Introduction
• Background
• Methods
• Results
• Discussion
• Conclusions

Discussion Only
This thematic analysis provides insights into HCV patients' experiences with PI based triple therapy. Before beginning their therapy, these patients were powerfully motivated to improve their health and achieve a cure. For dual therapy, patients have associated concerns regarding disease progression, loss of liver function and other potential health problems with treatment initiation.[43,44] However, this study group's homogeneously high motivation might not reflect the attitude of the majority of HCV patients in need for treatment. Studies have shown that large proportions of patients (10% - 44%) undergoing dual therapies typically discontinue treatment.[15,43,45] Although we included participants from three different outpatient clinics and used maximum variation sampling to ensure diverse characteristics and living circumstances, there might have been an earlier clinical selection of highly motivated patients treated with the then-newly-available triple therapies and the next generation of interferon-free treatments.

Soon after starting triple therapy, our highly-motivated study group found themselves struggling. The constitutive theme–"Fighting an uphill battle"–describes the patients' common existential experience of coping with the therapy's side effects and indirect negative consequences. Bell et al. describe similar existential treatment experiences among cancer patients receiving adjuvant chemotherapy.^[46] However, in contrast to cancer patients, who saw their symptoms as a means of tracking treatment effectiveness and increasing the possibility of remission, this study's HCV patients indicated beliefs congruent with research on triple therapy, i.e., that it numerous side effects, including possible life threatening adverse events, are to be expected, but that no associations exist between symptoms and success.^[18,47]

In this study, despite information from healthcare providers and research oriented treatment reports, the symptoms experienced surpassed the patients' expectations (as described in the "Encountering surprises" subtheme). Across chronic conditions, high symptom numbers, high symptom distress and low perceived symptom manageability have negative impacts on health outcomes including quality of life and medication adherence.^[48,49] Given the high number of HCV patients who commonly interrupt dual therapy and the high symptom burden of triple therapy, it can be hypothesized that mitigating patient distress via early symptom management support will increase successful completion of therapy and would decrease dropout rates in less persistent patient groups. And while even healthcare providers were occasionally surprised by the severity and diversity of the new treatment's side effects, the first step of effective symptom management is to assess patients' perceptions of their symptoms.^[50] However, our records illustrate very clearly that the participants' symptom experiences were often so foreign to them that only metaphoric language was sufficient to explain them. Therefore, standard biomedical symptom assessment by health care providers might not be sufficient to capture the details of symptoms or symptom clusters that impact safety, adherence and treatment persistence. And with the prospect of HCV treatment options appearing in the near future, a proactive and patient-oriented system of symptom assessment will remain an important component of clinical HCV management. On the one hand these treatments are expected to entail fewer and less severe adverse events; on the other, they will also be used in patients in advanced stages of the disease, suffering co-morbidities and living in more complex circumstances.
As described above in the subtheme "Reaching the limits of systems" the therapy's drastic physical and emotional effects fundamentally disrupted participants' everyday lives and severely limited their social interactions. Similar phenomena have been described for symptomatic but untreated HCV patients, as well as for other chronic conditions.^[51]

However, the radical social changes described by our study participants appeared heavily influenced by their fear of stigmatization. In order to protect themselves from negative social consequences, it is common for patients with stigmatized infectious diseases such as HIV and HCV to make careful disclosure decisions and in some cases conceal their conditions as fully as possible.^[52–54] Our illness-experienced study group described a range of selective disclosure management strategies that had apparently been effective before the start of their triple therapy. During treatment, though, the sudden appearance of visible symptoms led to isolation when support was most needed. In some cases, though, the perception of societal rejection might simply have been internalized, i.e., the fear of stigmatization may have led some to project it onto those around them. Recent evidence shows promising approaches to combatting internalized stigma (self-stigmatization) by improving both self-esteem and help-seeking behavior.^[55,56] To minimize stress and improve social support during HCV treatment, healthcare providers should discuss stigmatization fears and disclosure management strategies during consultations both before and during treatment.

The importance of social support is also apparent in the "Reaching the limits of systems" subtheme. Participants recalled both how their symptoms sometimes impaired their judgment and how, during these periods of diminished capacity, the support of family members and close friends was crucial. The positive effects of social support on chronically ill patients' health outcomes is well documented. For example, for patients living with HIV and receiving antiretroviral treatment, a stable partnership is associated with a slower progression to AIDS or death;^[57] and among patients living with HCV, those who are married are more likely to complete dual therapy.^[43] In addition to companionship, close social contact is known to have multifaceted benefits, including emotional, instrumental, informational support.^[34,58,59]

Since study patients revealed problems with judgment and efficacy concerning sometimes life threatening symptoms, a sound knowledge of HCV treatment and decision making skills is important not only for patients but for their close support persons. This requires healthcare providers to identify close support persons and integrate them into patient education programs. Where social contact with support persons is limited, professional support, e.g., community care, should be intensified.
Based on current evidence and clinical expertise, difficulties in adherence with the complex triple therapy regimens are to be expected.^[18,28,59] Surprisingly, this study's patients did not raise the issue of medication management. However, as some patients mentioned difficulties when asked, adherence issues may simply have been eclipsed by the intensity of the medications' side effects. Given that heavy symptom burdens (often much lighter than those described by this study's patients) are known to impact adherence, and that poor adherence to dual therapy is known to impact virological response,^[25–27] it is important to integrate non-judgmental adherence assessment into routine clinical care.

The insights provided by this study illustrate the need to assess patient perspectives of new treatment options in 'real-life' settings–as opposed to those of clinical trials. In clinical care, clinicians routinely treat patients who would have been excluded from clinical trials due to medical, social or behavioral problems. Research shows that exactly such medical or socio-behavioral challenges impair results in patients with HCV.^[42,60,61] Therefore, despite the availability of new HCV treatment options, it remains important to assess patients' treatment experiences with various other regimens where, based on information from clinical trials, these treatments offer higher tolerability and manageability. Furthermore, considering the extremely high cost of the currently-available IFN-free regimes with improved tolerability, it can be expected that they will not be used in all countries.

Full Text

At The Crossroads, Part 6: Veterans Harder Hit By Hep C

Sen. Bernie Sanders

A new series from Rhode Island Public Radio

At The Crossroads, Part 6: Veterans Harder Hit By Hep C

In our ongoing series about hepatitis C, we look now at one of the hardest hit populations: veterans. Hep C is three times more prevalent among vets than in the general population. The Veterans Health Administration has the country’s largest hepatitis C screening and treatment program in the country. But that program is struggling to pay for new treatments – and the rising number of veterans who need them.

Listen or read part 6, here or view the complete series, here. 

About the series:
Hepatitis C infects an estimated five million Americans, though most of them don’t know it. But deaths from hepatitis C are on the rise in baby boomers. And throughout New England, new infections are creeping up among a younger generation. Less than a year ago, their only options for treatment were complicated regimens of injections that didn’t always lead to a cure. But brand new drugs could change everything. That is, if the cost doesn’t break us.

Acknowledgments
This series was produced by Kristin Gourlay, and edited by Catherine Welch, as a project for The California Endowment Health Journalism Fellowships, a program of the USC Annenberg School for Communication and Journalism.

High costs threaten veterans' access to hepatitis C drug Sovaldi

Senate Panel Probes Exorbitant Prices for Hepatitis C Drugs 

WASHINGTON--(ENEWSPF)--December 3, 2014 – The Senate Veterans’ Affairs Committee held a hearing today on exorbitant prices charged by drugmakers for new treatments for hepatitis C, a liver disease that claims about 15,000 lives a year in the United States.

Gilead, the leading manufacturer of the drugs, refused to testify at the hearing about the $84,000 it charges for a 12-week regimen of Sovaldi and the $94,500 price tag for a newer drug, Harvoni. The price per pill is about $1,000 for Sovaldi $1,125 for Harvoni.

Even with bulk-purchase discounts, the Department of Veterans Affairs spent $370 million in the past year on new treatments. Outlays are projected to soar by an additional $1.3 billion for the next two years.

“What we are looking at is a very excessive profit,” said Sen. Bernie Sanders (I-Vt.), the committee chairman. He called it “deplorable” and a “moral issue” that the life-saving drug may have to be rationed because the price makes it unaffordable for all who need it.

The treatment cost is especially significant to the VA because the disease affects veterans – particularly Vietnam-era veterans – at a rate higher than the general population. Approximately 174,000 veterans currently enrolled in VA have been diagnosed with hepatitis C.

Sovaldi is on pace to become the highest grossing drug in history. Approved by the Food and Drug Administration late in 2013, sales totaled $2.27 billion in the first quarter of 2014 and $3.48 billion in the second quarter. Gilead bought the rights to market the drug from another company, which had planned to charge less than half as much for the medication. “Did Gilead purchase the company knowing it could more than double the price and pay for its investment in one year?” asked John Rother of the National Coalition on Health Care.

Robert Weissman, president of the consumer rights group Public Citizen, testified that Gilead is making $200 million a week on Sovaldi. He said treatments are useful only if they are accessible. “We’ve now reached a point where treatments will increasingly be restricted and rationed because brand-name drug companies have used monopolies to price them out of reach.”

The introduction of the costly but effective treatments “holds the promise of eradicating this disease in infected veterans,” according to Michael Valentino, a pharmacist who is the VA’s chief Pharmacy Benefits Management consultant. But he told the committee that the cost of the new therapies “remains a major challenge.”

High costs threaten veterans' access to hepatitis C drug Sovaldi

Stars and Stripes

Published: December 3, 2014

WASHINGTON — A new drug holds the potential to cure hepatitis C in tens of thousands of veterans but will require billions in new spending to cover the cost, Department of Veterans Affairs officials told a Senate panel Wednesday....

Sen. Richard Burr, R-N.C., said companies such as Gilead take large financial risks and navigate a testing and approval “valley of death” when developing new drugs.

“Innovation is expensive … I think the one thing we agree on is we don’t want to give up innovation,” Burr said....

Instead of attacking prices, he said Congress and the VA should look at how much could be saved in the long-term by treating veterans known to have hepatitis C....

“I believe the price of this particular drug should be looked at on the macro level,” Burr said.

Still, it remains unclear how the VA will deal with the high costs of treatment. Valentino said the department expects more new hepatitis C drugs to be released this month and next year, which could provide veterans alternatives to Sovaldi...

Continue reading...

Reducing the cost of new hepatitis C drugs
Daclatasvir, Harvoni (ledipasvir/sofosbuvir) and Sovaldi.
An index of articles & research weighing the pros and cons over the high price of hepatitis C drugs.

Noninvasive Alternatives to Assess Liver Fibrosis: Ready for Prime Time?

Medscape

Noninvasive Alternatives to Assess Liver Fibrosis: Ready for Prime Time?

William F. Balistreri, MD

December 02, 2014

A Common Clinical Scenario

A healthy, asymptomatic 45-year-old woman with newly diagnosed hepatitis C virus (HCV) infection presents for consultation. Her questions relate not only to treatment options but also to her prognosis: "How much damage has the virus caused?" "Is my liver scarred?" She is informed that despite an unremarkable physical examination, the gold standard for determining the extent of fibrosis is liver biopsy. Having researched her diagnosis, the patient expresses her understanding but has valid concerns that this invasive procedure is subject to not only sampling/interpretation error but also, albeit rarely, potentially life-threatening procedure-related complications. She asks, "Is there a noninvasive way to determine the extent of scarring?"

This is an increasingly common clinical scenario owing to various factors.

Awareness of HCV has increased since the recent Centers for Disease Control and Prevention recommendations that everyone in the baby boomer generation undergo a one-time screening test.[1] This is a major advance in public health, but it brings the potential of discovering hundreds of thousands of infected persons.[2] In addition, widespread excitement has been generated by the emergence of new HCV antivirals that offer a high probability of a cure.[3]

Along with these developments in HCV, there is also the reality that the global epidemic of obesity will bring an increasing number of patients with fatty liver disease to our offices.[4]

The flood of patients with liver disease will challenge clinicians to determine the prognosis and eligibility for treatment and to gauge the response to any intervention.

Thus, there is significant interest in the development and validation of noninvasive alternatives to biopsy in the assessment of the extent of liver disease, specifically the degree of fibrosis and the pace of progression. The emergence of these tools will have a significant impact on clinical research as well as the practice of hepatology.
Noninvasive Options for Fibrosis Assessment

The proposed methods of fibrosis assessment in a variety of liver diseases are based on clinical, biochemical, and radiologic variables and are often used in combination. Specifically, the use of serum biomarkers of fibrosis and apoptosis, and several imaging modalities to assess liver stiffness, have been introduced and validated. These noninvasive indices of liver fibrosis offer an enhanced ability to prognosticate and stratify disease, thus improving patient care; they will also inform the development of antifibrotic therapies.[5,6]

Despite this recent progress, questions remain regarding the diagnostic validity, cut-off and threshold values for the degree of fibrosis, cost, and broad applicability of each test, which should be answered with more data obtained through systematic reviews of studies.[7]

Serum Biomarkers

The practical advantages of emerging serum biomarkers include their high applicability and interlaboratory reproducibility, as well as their potential widespread availability. However, these biomarker panels require careful clinical correlation for critical interpretation of results. In addition, serum biomarkers often fail to discriminate adequately between lesser grades of fibrosis. Nevertheless, biomarkers are potentially useful monitoring and prognostic tools, with the ability to predict clinical outcome on the basis of repeated assessment of the ongoing pathophysiologic process of fibrogenesis.

The commonly used biomarkers for the detection of liver fibrosis include simple measures, such as the aspartate aminotransferase-to-platelet ratio index (APRI),^[6,8] as well as several marketed products or validated algorithms that assess extracellular matrix turnover (fibrogenesis). These include:

• FibroMeter™ (Echosens; Paris, France)^[9];
• FibroTest-ActiTest® (Biopredictive; Paris, France); HCV FibroSure® (LabCorp; Burlington, North Carolina)^[10,11];
• HepaScore^[12] (also known as FibroScore);
• Enhanced liver fibrosis (ELF) panel^[13,14]; and
• Fibrosis-4 (FIB-4) index.^[15,16]

Each is derived from a panel of analytes that have been shown to predict the process or extent of fibrogenesis; please consult the cited references for specific details.

To varying degrees, these tests have achieved acceptance. Vergniol and colleagues[15] reported the value of several of these noninvasive tests in monitoring patients with chronic HCV infection and in predicting their outcome over a 3-year evolution of liver fibrosis. A meta-analysis by Xiao and colleagues[16] suggested that APRI and FIB-4 can identify hepatitis B virus (HBV)-related fibrosis with moderate sensitivity and accuracy.

The FibroTest was shown to correlate with survival and to have a similar 5-year prognostic value to that of liver biopsy in patients with a variety of liver diseases, such as chronic HBV or HCV and alcoholic liver disease.[17] Vallet-Pichard and colleagues[18] validated the simple, inexpensive FIB-4 index, which combines standard biochemical values (platelets, alanine aminotransferase [ALT], aspartate aminotransferase [AST]) and age, as an accurate method for assessing liver fibrosis, concordant with FibroTest results.

Imaging Techniques

Transient Elastography

Over the past 5 years, transient elastography (TE) has become accepted as a noninvasive marker of fibrosis. TE, which relies on sonic detection of liver stiffness to predict hepatic fibrosis, has been validated in patients with chronic hepatitis.^[19] TE methodology offers several distinct advantages: a brief procedure time, immediate availability of results, and the option of performing the procedure in real time at the bedside or in the outpatient clinic.

TE has some limitations. As with any tool, the results are often in the hands of the user. Interpretation must be correlated with the clinical context and other test results (biochemical, radiologic, and endoscopic).^[20] In addition, liver stiffness may be overestimated in the presence of confounding factors, such as obesity, extrahepatic cholestasis, and congestive heart failure.^[21] Appropriate cut-off values for diagnosing fibrosis and distinguishing cirrhosis must be further defined for each assay.^[22] Numerous published studies, some of which are summarized here, have addressed the rationale, reliability, and limitations of this technique.

Wong and colleagues examined the accuracy of TE as measured by FibroScan^® (Echosens; Paris, France) among patients with nonalcoholic fatty liver disease (NAFLD).^[23]Liver stiffness increased significantly with fibrosis. TE was highly accurate for detecting significant/advanced fibrosis and cirrhosis. Its accuracy was not affected by body mass index (BMI) or steatosis grade and was similar to that of other clinical and biochemical noninvasive measures: APRI, FIB-4, NAFLD fibrosis score, and BARD score (derived from BMI, AST/ALT ratio, and the presence of diabetes).

Degos and colleagues^[24] compared the accuracy of TE, assessed using FibroScan, with that of serum biomarkers in the prediction of significant biopsy-proven fibrosis in patients with chronic viral hepatitis. The overall accuracy of FibroScan was significantly higher than that of biomarkers.

Pang and colleagues^[17] tested the ability of liver stiffness measurement by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease. They used Cox regression to determine the independent association between liver stiffness and hepatic complications or death. After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications. TE may help estimate prognosis and guide management of patients with chronic liver disease.

Significant fibrosis may be present in patients with NAFLD despite normal liver tests and ultrasonography.^[5,25] Liver stiffness measurement by TE proved to be useful and specific to screen for cirrhosis in the general population and to detect undiagnosed chronic liver disease in apparently healthy persons.^[26,27] Liver stiffness values in the general population were found to be influenced independently by sex, BMI, and the metabolic syndrome.^[28,29]

Liver stiffness values vary after a test meal, presumably owing to adaptation of the hepatic microcirculation to increased portal blood flow; postprandial hyperemia is associated with a greater increase in portal pressure in patients with cirrhosis.^[30,31] Arena and colleagues^[32] characterized the "confounding" increase in liver stiffness after a standardized meal in patients with chronic HCV infection at different stages of evolution of the process of fibrogenesis. They detected evidence of the confounding effect of a meal on the accuracy of liver stiffness measurements for the prediction of fibrosis stage in patients with chronic HCV hepatitis and suggested that patients should fast for 120 minutes before TE is performed.

Magnetic Resonance Elastography

Several MRI techniques have also been proposed for assessing hepatic fibrosis. The most common approach is magnetic resonance elastography (MRE).[5,33-37] MRE quantitatively measures and visualizes propagating acoustic shear waves that progress through liver tissue.[5,38] This test has been of value in the assessment of chronic liver disease in children, a population in which determination of the stage of liver injury is especially limited by lack of validated noninvasive biomarkers of histologic severity. In a case series of 35 children with chronic liver disease, including severely obese children, Xanthakos and colleagues[38] demonstrated that MRE is feasible and accurate in detecting significant hepatic fibrosis.
Ultrasonography

Acoustic radiation force impulse (ARFI) imaging is a promising method that involves the mechanical excitation of tissue using short-duration acoustic pulses. The ARFI method can be embedded into a conventional ultrasonographic scanner to allow formal examination of the hepatic parenchyma as well.[7] Several published studies have addressed the rationale, reliability, and limitations of this technique; preliminary results suggest very similar performance to that of TE, although further validation is warranted.

Leung and colleagues[6] documented the utility of shear-wave (SW) elastography for assessing liver fibrosis in patients with chronic hepatitis B and compared its performance with that of TE. SW elastography of the liver, SW elastography of the spleen, and TE of the liver were compared and correlated with biopsy-derived fibrosis scores. SW elastography of the liver showed significantly higher accuracy than TE of the liver and SW elastography of the spleen in all fibrosis stages. SW elastography of the liver had a higher success rate than TE of the liver (98.9% vs 89.6%). Real-time SW elastography was also shown to be accurate for assessing liver fibrosis in patients with chronic hepatitis C.[39]

Spleen stiffness as a predictive model. Takuma and colleagues[40] also documented the prognostic value of spleen stiffness, as detected by ultrasonography (ARFI imaging), in the evaluation of patients with cirrhosis, specifically differentiating patients at low risk for decompensation from those at high risk. Similar results were documented in other centers and in a pediatric population.[41,42]
Not the End of Liver Biopsy Yet

It seems that these noninvasive techniques have had an impact by decreasing the number of liver biopsies performed. In addition, such modalities as MRE have given us a "number" to share with the patient—one that reflects the degree of liver fibrosis.

However, the story is incomplete. More data are needed, including studies that compare strategies using TE, MRE, ARFI, or biomarkers (perhaps in combination) in various populations. Finally, the cost-effectiveness of each screening/monitoring strategy must be further evaluated before broad implementation can be recommended.

Source - Medscape

Parliamentary inquiry to examine Australia's hepatitis C 'epidemic'

Parliamentary inquiry to examine Australia's hepatitis C 'epidemic'

Natasha Boddy
Canberra Times reporter
View more articles from Natasha Boddy

The organisation's chief executive Helen Tyrrell said hepatitis C had been neglected as an epidemic in Australia. 

"It's really in the shadows of many other blood-borne viruses which actually have a lower prevalence but much higher profile in the community," she said.

"The issue with hep C at the moment is that we're really at a watershed moment where we've got 250,000 people in Australia living with hepatitis and about three-quarters of those are already over the age of 40 and we know that puts them into the 'liver danger zone' which means they are at the point where their risk of serious liver disease is significantly increased."

Continue reading.... 

Probiotics for Cirrhosis?

bacteria in the intestinal microbiota

Probiotics for Cirrhosis?

A probiotic solution significantly reduced the risk of hospitalization for hepatic encephalopathy and markers of liver disease severity in patients with cirrhosis, researchers report in the December issue of Gastroenterology.

Hepatic encephalopathy develops in 50%–70% of patients with cirrhosis; fewer than 50% of these patients survive for 1 year. Rifaximin and lactulose are commonly used to try to prevent hepatic encephalopathy, but there are concerns about their cost and side effects. Many patients develop breakthrough episodes of hepatic encephalopathy despite prophylactic treatment with these agents.

Hepatic encephalopathy has been linked to alterations in the intestinal microbiota, increased production of gut-derived toxins such as ammonia and indoles, and endotoxemia, which lead to systemic and cerebral inflammation.

Probiotics can alter numbers, composition, and functions of bacteria in the intestinal microbiome and reduce levels of ammonia. Radha K. Dhiman et al therefore performed a randomized controlled trial to determine whether probiotics could prevent recurrence of hepatic encephalopathy and improve liver function in patients with cirrhosis.

At a hospital in India, 130 patients with cirrhosis who had recovered from an episode of hepatic encephalopathy in the previous month were randomly assigned to groups given a probiotic preparation (VSL#3, 9 × 1011 colony-forming units per sachet) or placebo (controls) each day for 6 months.

VSL#3 contains 4 Lactobacillus species (L paracasei, L plantarum, L acidophilus, and L delbrueckii subspecies bulgaricus), 3 Bifidobacterium species (B longum, B infantis, and B breve), and Streptococcus thermophiles.

After the 6 month period ended, only 34.8% of subjects in the probiotic group had developed hepatic encephalopathy, compared with 51.6% in the control group, although this difference was not significant.

However, significantly fewer patients in the probiotic group were hospitalized for hepatic encephalopathy (19.7% vs 42.2% of controls) or for complications of cirrhosis (24.2% vs 45.3% of controls). The mean time to hospitalization for any reason was 136 days in the probiotic group and 109 days in the placebo group.

Child–Turcotte–Pugh and model for end-stage liver disease scores (indicators of liver disease) improved significantly from baseline to 6 months in the probiotic group, but not in the placebo group.

There were no adverse events related to VSL#3. Thirty patients died during the study: 14 in the probiotic group and 16 in the placebo group.

Fasting blood ammonia levels decreased among patients in the probiotic group and increased among patients in the placebo group, although these were not statistically significant. Plasma indole levels decreased significantly only in the probiotic group.

Although plasma levels of the inflammatory cytokines tumor necrosis factor (TNF), IL1B, and IL6 decreased significantly in the probiotic group, there was no significant change in the placebo group. Plasma levels of renin and brain-type natriuretic peptide (BNP) also decreased significantly in the probiotic group but not the placebo group.

How could a probiotic reduce markers of liver disease, complications of cirrhosis, and even risk of hospitalization? Dhiman et al explain that bacterial overgrowth and impaired intestinal barrier integrity in patients with cirrhosis leads to endotoxemia. Endotoxemia initiates liver damage through its interaction with Toll-like receptors, which activate immune and inflammatory responses. Systemic inflammation and infection exacerbate the symptoms of hepatic encephalopathy in patients with all grades of cirrhosis. Production of inflammatory cytokines such as TNFa, IL1b, and IL6 can the increase the cerebral effects of ammonia.

Probiotics have been shown to improve the integrity of the gut epithelium, promote innate immunity in the gut, and reduce local and systemic inflammation.

Dhiman et al propose that in the patients receiving the probiotics, significant reductions in renin, aldosterone, and BNP probably resulted from improved cardiac function, systemic hemodynamics, and increased renal blood flow following reductions in inflammatory cytokines. However, further studies of hemodynamic parameters are needed to confirm model.

The authors conclude that probiotic use significantly reduces the risk of hospitalization, related primarily to the development of fewer complications and episodes of breakthrough hepatic encephalopathy in patients with cirrhosis. They say that this could translate into significant cost savings.

In an editorial that accompanies the article, David W. Victor, III and Eamonn M.M. Quigley state that additional studies, to demonstrate a clinically meaningful reduction in recurrence of hepatic encephalopathy, are required before this or any other probiotic can be recommended for treatment of patients.

They say it is also important to identify the bacterial populations whose presence, or absence, affect risk for hepatic encephalopathy. This would facilitate development of probiotic formulations best suited for therapy or prevention.

Source - http://journalsblog.gastro.org/probiotics-for-cirrhosis/