News: Cirrhosis

News Cirrhosis

Cirrhosis Blog Updates

Nov 2012
Chronic HCV infection: epidemiological and clinical
relevance

May 2012
Audio - Minimal hepatic encephalopathy Complications of Cirrhosis
Experts Offer Guidance on Use of DAAs for Difficult-To-Treat Hep C Patients
ISSUE: MAY 2012 | VOLUME: 63:5
Cirrhotic patients who previously received the standard two-drug therapy and then received telaprevir in combination with pegylated interferon (Peg-IFN) and ribavirin had improved..
Continue Reading At:gastroendonews.com

Triple Therapy for Hepatitis C-Maximizing Opportunities and Avoiding Mistakes
A special supplementary issue of Gastroenterology with
full text viral hepatitis review articles and commentaries available through open access.
Click here to view an index of articles.

March 2012
Tumor response assessment to sorafenib in patients with advanced hepatocellular carcinoma: do we need new criteria?

May 2012
Complications of Cirrhosis
Purpose of review Chronic liver disease (CLD) causes significant morbidity and mortality, mainly due to complications [hepatic encephalopathy, ascites,
hepatorenal syndrome (HRS), and esophageal variceal hemorrhage (EVH)]. Studies of the complications, management and outcomes in patients with CLD over the past 18 months are reviewed.

Feb 2012
JOURNAL OF HEPATOLOGY
VOLUME 56, SUPPLEMENT 1, PAGES S1–S122
Management of Liver Diseases 2012
Management of bacterial infections in cirrhosis
Management of critically-ill cirrhotic patients
Management of hepatic vascular diseases
Management of alcoholic hepatitis
Managing systemic symptoms in chronic liver disease
The interaction of metabolic factors with HCV infection:
Does it matter?
Anti-fibrotic therapy: Lost in translation?
Management of HCC
Antiviral strategies in hepatitis C virus infection
Trends in liver transplantation 2011
Management of treatment failure in chronic hepatitis B
Download PDF Here

Video
New and experimental oral drugs to treat hepatitis C
Also Current Recommendations for Using Telaprevir and Boceprevir in Patients With Advanced Fibrosis or Cirrhosis

Jan 2012
Future treatment of patients with HCV cirrhosis

February 2012
Of all hepatitis C virus (HCV) patients, those with cirrhosis are most in need of treatment because of increased morbidity and mortality. Treatment with pegylated-interferon (PEG-IFN) and ribavirin (RBV) (PR) has definitely shown the benefits of successful treatment by improving fibrosis, causing the regression of cirrhosis and reducing and preventing cirrhosis-related complications. However, the sustained virological response (SVR) is lower in patients with cirrhosis. First generation protease inhibitors (boceprevir and telaprevir) in combination with PR are a major advancement in the treatment of both naïve and treatment-experienced genotype 1 patients. In naïve patients, the SVR rate with the triple regimen with boceprevir was increased by 14% in patients with severe fibrosis or cirrhosis compared with PR. This benefit was lower than that observed in patients with mild or moderate fibrosis (30%). The SVR rate of the triple regimen with telaprevir was increased by 10–30% compared with PR in patients with severe fibrosis or cirrhosis compared with nearly 30% in patients with mild or moderate fibrosis. In treatment-experienced patients, previous relapsers have the highest increase in SVR with the triple regimen compared with PR, whatever the status of fibrosis. Previous partial or non-responder patients with cirrhosis had lower SVR rates than those without cirrhosis. However, the benefits of telaprevir and boceprevir vs PR was maintained. Previous non-responder patients with cirrhosis benefited the least from treatment. The relapse rate was always higher and side effects were more frequent in patients with cirrhosis compared with those without. First generation protease inhibitors plus PR appear to be a new step forward in the management of HCV genotype 1 patients with cirrhosis...continue reading..

The Patient With Cirrhosis: Don't Miss This
David A. Johnson, MD
Dec 2011
Podcast:
Advanced Liver Disease Volume 19 Issue 3 August/September 2011
Advanced Liver Disease: What Every Hepatitis C Virus Treater Should Know
Identification and treatment of advanced hepatitis C virus (HCV) infection is often challenging. Accurate fibrosis staging can be performed only by liver biopsy. For patients with advanced fibrosis (Metavir score, F3 or F4), progression to decompensated liver disease occurs at a rate of approximately 5% per year and progression to hepatocellular carcinoma occurs at a rate of 1% to 2% per year

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

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

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

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

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

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

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

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

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

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

Can Early Responders Stop Treatment?

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

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

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

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

Promacta Could Ease Hepatitis C Treatment Complications Depending on the results of a study investigating Promacta for Hepatitis C blood-related treatment complications, this medication could become a valued addition to managing the side effects of Hepatitis C combination therapy.
Glaxo's Promacta May Turn Into Blockbuster Medicine, UBS Says
By Makiko Kitamura
Nov. 7 (Bloomberg) -- GlaxoSmithKline Plc's Promacta blood disorder medicine may generate as much as $2 billion in annual sales if the U.K.'s largest drugmaker can expand its use to the treatment of a condition associated with hepatitis C, according to UBS AG.

The medicine, already approved for sale in the U.S. to raise platelet counts in patients with a rare blood disorder, is being studied to extend use to patients with thrombocytopenia, a blood complication stemming from hepatitis C treatments. Glaxo will present results from the last of three stages of clinical testing required for regulatory approval on the new use at a medical meeting in San Francisco today.

Continue reading this entire article:
http://www.businessweek.com/news/2011-11-09/glaxo-s-promacta-may-turn-into-blockbuster-medicine-ubs-says.html?trkv=481538&trks=1298469

November

AASLD: Do Hepatitis C Patients with Cirrhosis Benefit from Adding Telaprevir?

Published on Tuesday, 15 November 2011 00:00 Written by Liz Highleyman © Russell Kightley

Adding telaprevir to pegylated interferon/ribavirin increased the likelihood of a cure for genotype 1 chronic hepatitis C patients with liver cirrhosis in the REALIZE trial, according to data presented at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011) last week in San Francisco.

The advent of hepatitis C virus (HCV) direct-acting antiviral agents has revolutionized treatment, but drugs such as the recently approved HCV protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis) have not yet been well studied in people with advanced liver disease -- a group that responds poorly to standard interferon-based therapy.

Stanislas Pol from Université Paris Descartes and colleagues performed a sub-analysis to assess the safety and efficacy of telaprevir plus pegylated interferon/ribavirin among prior non-responders with Child A stage cirrhosis in the pivotal REALIZE trial.

REALIZE compared 2 telaprevir regimens -- 12 weeks of telaprevir/pegylated interferon/ribavirin triple therapy followed by 36 weeks of pegylated interferon/ribavirin alone, or a 4-week pegylated interferon/ribavirin lead-in followed by 12 weeks of triple therapy and 32 weeks of pegylated interferon/ribavirin alone -- versus pegylated interferon/ribavirin standard therapy for 48 weeks.

Out of the total 662 participants in the trial, 578 had complete information about liver disease status at baseline; within this group, 143 patients had liver cirrhosis (fibrosis stage F4). The majority of participants were men and almost all were white. People with cirrhosis were slightly older than non-cirrhotics (54 vs 50 years) and were more likely to be prior null responders rather than partial responders or relapsers (36% vs 25%). Patients taking the 2 different telaprevir regimens were pooled.

Results

Overall, participants who received telaprevir triple had significantly higher sustained virological response (SVR) rates than those who received pegylated interferon/ribavirin standard therapy alone.
The benefit of adding telaprevir was seen across all fibrosis stages:
- Cirrhosis (stage F4): SVR 47% with telaprevir triple therapy vs 8% with pegylated interferon/ribavirin alone;
- Bridging fibrosis (stage F3): 67% vs 7%, respectively;
- Absent, minimal, or moderate fibrosis (stage F0-F2): 75% vs 22%, respectively.
The benefit of adding telaprevir was greatest for patients with better prior response and not appreciably different for null responders:
- Prior relapsers: SVR 84% with telaprevir triple therapy vs 7% with pegylated interferon/ribavirin alone;
- Prior partial responders: 34% vs 20%, respectively;
- Prior null responders: 14% vs 10%, respectively.
Looking only at telaprevir recipients, prior null and partial responders with cirrhosis had lower SVR rates than non-cirrhotics, but prior relapsers were similar:
- Prior relapsers: SVR 84% for cirrhotics vs 87% for absent-to-moderate fibrosis;
- Prior partial responders: 34% vs 77%, respectively;
- Prior null responders: 14% vs 41%, respectively.
32% of patients with cirrhosis experienced on-treatment virological failure, compared with 13% of non-cirrhotics.
12% and 5%, respectively, relapsed after completing therapy.
In a multivariate analysis of patients with cirrhosis, baseline ALT or AST and degree of prior response were significant predictors of response.
Among patients who experienced virological failure on telaprevir, there was no association between telaprevir resistance and fibrosis/cirrhosis stage.
Among patients with cirrhosis, side effects that occurred more often in the telaprevir arms than in the standard therapy arm included skin rash, pruritis (itching), and anemia.
15% of patients with cirrhosis and 12% of non-cirrhotic patients discontinued telaprevir due to adverse events.

"Telaprevir plus [pegylated interferon/ribavirin] resulted in higher SVR rates in treatment-experienced patients with cirrhosis compared with [pegylated interferon/ribavirin] alone," the researchers concluded. "Rates of discontinuation due to [adverse events] were slightly higher in cirrhotic versus non-cirrhotic patients."

Investigator affiliations: Université Paris Descartes, INSERM Unité 1016, and Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France; Department of Gastroenterology, Alfred Hospital, Melbourne, VIC, Australia; Università di Bologna, Bologna, Italy; Center for Liver Diseases and Department of Medicine, Inova Fairfax Hospital, Falls Church, VA; Hospital General de Valencia, Valencia, Spain; Alamo Medical Research, San Antonio, TX; Emilio Ribas Infectious Diseases Institute, São Paulo, Brazil; Queen Marys University of London, Institute of Cell and Molecular Science, London, UK; Medical University of Warsaw, Warsaw, Poland; Janssen Pharmaceuticals, Paris, France; Tibotec Inc., Titusville, NJ; Tibotec BVBA, Beerse, Belgium; Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany.

11/15/11

Reference

S Pol, SK Roberts, P Andreone, et al. Efficacy and safety of telaprevir-based regimens in cirrhotic patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: subanalysis of the REALIZE Phase III study. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 31.

Hep C Trial Reports Good Results for Alisporivir November 18, 2011
Representing a new type of Hepatitis C drug, the debut of Alisporivir (a cyclophilin inhibitor) delivers encouraging news for interferon-free Hepatitis C treatment.

November 14, 2011

Interferon-Free Alisporivir Treatment Showing Promise in Genotype 2/3 Trial

Alisporivir, a once-daily drug being developed by Novartis at the forefront of a new class of hepatitis C virus (HCV) compounds known as cyclophilin inhibitors, is showing promise as a component of interferon-free therapy for people with genotype 2 or 3 HCV infection, according to new results from a Phase II study reported in San Francisco at the 62nd annual meeting of the American Association for the Study of Liver Diseases.

Nearly half of all study volunteers using the drug in combination with ribavirin, but without interferon, have undetectable HCV levels after six weeks of treatment, reported Jean-Michel Pawlotsky, MD, of the University of East Paris and his colleagues. In addition, roughly a third of the genotype 2/3 patients in the study had undetectable HCV levels at the six-week mark of therapy with alisporivir alone--use of the drug without either pegylated interferon or ribavirin.

Continue reading this entire article:
http://www.aidsmeds.com/articles/alisporovir_
interferon_hcv_1667_21445.shtml?trkv=481538&trks=1298469