News Cirrhosis
May 2012
DDW-Statins Shown to Be Safe in Patients With Cirrhosis Complications of Cirrhosis Cirrhosis - Risks of Eating Raw Oysters New Antivirals Show Poor Safety in Hepatitis C With Cirrhosis April 2012 Heart Surgery Safe for Compensated Cirrhosis Patients Summary Of The 47th European Association for the Study of the Liver EASL Cirrhosis burden expected to climb in older Americans Findings Confirm Benefits of Albumin in Treating Cirrhosis Patients Undergoing Large-Volume Paracentesis Bacterial resistance in cirrhotic patients: An emerging reality March Cirrhotic patients experience increased daytime sleepiness from higher ammonia levels Source Italian and Swiss researchers confirm that induced hyperammonaemia significantly increases daytime sleepiness in patients with cirrhosis. The findings available in the March issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases, show that higher blood levels of ammonia reduced the ability of cirrhotic patients to produce restorative sleep. Chronic liver disease can lead to cirrhosis—a condition where scar tissue replaces healthy tissue, resulting in decreased blood flow through the liver and reduced liver function. Viral hepatitis, heavy alcohol use and obesity are among the causes of cirrhosis according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). In patients with chronic liver failure neuropsychiatric abnormalities may arise—termed hepatic encephalopathy (HE)—which experts believe to be due to neurotoxic substances that originate in the gut and are not cleared by the liver, such as ammonia. HE is common following a gastrointestinal bleed, which can be simulated by the oral administration of a mixture of protein mimicking that contained in blood ('amino acid challenge'; AAC). To investigate the effects of excess ammonia and HE on sleep-wake patterns in patients with cirrhosis, Dr. Sara Montagnese and colleagues from the Dipartimento di Medicina in Padova, Italy and the Institute of Pharmacology and Toxicology in Zurich, Switzerland, induced hyperammonaemia in participants by an AAC. Ten cirrhotic patients and ten healthy controls underwent eight days of sleep quality monitoring, neuropsychiatric/wake and sleep EEG assessment prior to and following the AAC, and hourly ammonia and sleepiness assessments for eight hours post-AAC. "Our study found that induced hyperammonaemia led to a significant increase in daytime sleepiness in both patients and healthy volunteers," said Dr. Montagnese. The authors also report changes to the EEG architecture of a sleep episode (nap) in patients with cirrhosis, which they believe points to a reduced ability to produce restorative sleep. Dr. Montagnese concludes, "Our findings have important clinical implications in that subjective sleepiness may be used as a surrogate marker for HE." The authors also suggest that strategies aimed at reducing daytime sleepiness may result in improved sleep at night. More information: "Induced Hyperammonaemia may Compromise the Ability to Generate Restful Sleep in Patients with Cirrhosis." A Bersagliere, ID Raduazzo, M Nardi, S Schiff, A Gatta, P Amodio, P Achermann and S Montagnese. | Also See : Digest
2010/2011 Cirrhosis Specialty News Digest Cirrhosis Blog Updates 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 SVR compared with patients who received Peg-IFN and ribavirin alone. However, among those with cirrhosis, SVR rates peaked at 47% in previous responders and were lower for previous null responders. The study also found that cirrhotic patients with several baseline factors—high baseline alanine aminotransferase (ALT)or aspartateaminotransferase (AST) levels—were more likely to achieve SVR following telaprevir triple therapy..... 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? By Dr Mohmed Bouattour Sorafenib, an oral multi-tyrosine kinase inhibitor, is the first and so far the only drug that has shown overall survival benefit in patients with advanced hepatocellular carcinoma (HCC) in two large multicenter, double-blind, placebo-controlled randomized phase III trials [1-2]. Despite the survival benefit in this population, sorafenib has been infrequently associated with changes in tumors dimensions, challenging standard RECIST criteria [3]. Tumor shrinkage and dimensional change, usually assessed to define tumor response of cytotoxic drugs based on the morphological RECIST criteria, was observed in less than 5% of patients. Furthermore, changes in tumor angiogenesis are observed such as decrease in the number of vessels in tumor masses and the appearance of large areas of intratumor necrosis (Figure 2). This feature is acknowledged to reflect the antitumor activity of antiangiogenic drugs that does not always translate into changes in the diameter of the tumor, making the radiological evaluation of efficacy using standard RECIST criteria often inappropriate........... 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
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 |