Elena Vezali1, Alessio Aghemo, Massimo Colombo. 1. Centro A.M. e A. Migliavacca, Unità Operativa di Gastroenterologia 1, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Abstract
BACKGROUND: Cirrhosis developing during chronic infection with the hepatitis C virus (HCV) poses a risk of anticipated liver-related death, therefore representing a dominant indication to anti-HCV therapy. OBJECTIVE: This review highlights the efficacy and safety of treatment of HCV infection in cirrhotic patients with respect to the clinical stage of the disease. METHODS: The PubMed, MEDLINE, EMBASE, and Cochrane databases, as well as the conference proceedings from the annual meetings of the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver, were searched for articles published in English from January 1990 through May 2010, fulfilling the following criteria: (1) randomized, prospective observational, retrospective, or meta-analysis; (2) involving adult patients with chronic HCV infection; and (3) data (fibrosis stage, treatment regimen, efficacy, safety) available for cirrhotics. Reviews were excluded. Search terms included chronic hepatitis C, fibrosis, cirrhosis, interferon alfa, ribavirin, hepatocellular carcinoma, and liver decompensation. RESULTS: Forty-five studies were identified. The rates of sustained virologic response to pegylated interferon in combination with ribavirin ranged from 10% to 44% for HCV genotypes 1/4 to 33% to 72% for genotypes 2/3 in compensated cirrhosis, while falling to 0% to 16% and 44% to 57%, respectively, in the decompensated stage, compared with 29% to 55% for genotypes 1/4 and 70% to 80% for genotypes 2/3 in noncirrhotic patients (compensated cirrhosis vs no cirrhosis: P < 0.001 for genotypes 1/4 and P = 0.002 for genotypes 2/3; decompensated cirrhosis vs no cirrhosis: P < 0.001 for all genotypes). HCV clearance was associated with a reduced risk of liver decompensation, hepatocellular carcinoma development, liver-related mortality, and hepatitis recurrence after liver transplantation. Treatment during compensated cirrhosis proved to be most cost-effective versus treatment after decompensation or a no-treatment strategy. Headache (54%), irritability (38%), fatigue (34%), and nausea (30%) were the most common adverse events in compensated patients, while anorexia (100%), fatigue (59%), neutropenia (53%), and thrombocytopenia (50%) were most common in decompensated patients. CONCLUSIONS: Anti-HCV treatment in cirrhotic patients was less effective than in noncirrhotic patients. Viral eradication reduced the risk of liver complications and improved survival in noncirrhotics. Based on effectiveness and tolerability data, therapy has a significant effect in patients with compensated cirrhosis, while decompensated patients need to weigh the risks versus benefits of treatment.
BACKGROUND:Cirrhosis developing during chronic infection with the hepatitis C virus (HCV) poses a risk of anticipated liver-related death, therefore representing a dominant indication to anti-HCV therapy. OBJECTIVE: This review highlights the efficacy and safety of treatment of HCV infection in cirrhoticpatients with respect to the clinical stage of the disease. METHODS: The PubMed, MEDLINE, EMBASE, and Cochrane databases, as well as the conference proceedings from the annual meetings of the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver, were searched for articles published in English from January 1990 through May 2010, fulfilling the following criteria: (1) randomized, prospective observational, retrospective, or meta-analysis; (2) involving adult patients with chronic HCV infection; and (3) data (fibrosis stage, treatment regimen, efficacy, safety) available for cirrhotics. Reviews were excluded. Search terms included chronic hepatitis C, fibrosis, cirrhosis, interferon alfa, ribavirin, hepatocellular carcinoma, and liver decompensation. RESULTS: Forty-five studies were identified. The rates of sustained virologic response to pegylated interferon in combination with ribavirin ranged from 10% to 44% for HCV genotypes 1/4 to 33% to 72% for genotypes 2/3 in compensated cirrhosis, while falling to 0% to 16% and 44% to 57%, respectively, in the decompensated stage, compared with 29% to 55% for genotypes 1/4 and 70% to 80% for genotypes 2/3 in noncirrhotic patients (compensated cirrhosis vs no cirrhosis: P < 0.001 for genotypes 1/4 and P = 0.002 for genotypes 2/3; decompensated cirrhosis vs no cirrhosis: P < 0.001 for all genotypes). HCV clearance was associated with a reduced risk of liver decompensation, hepatocellular carcinoma development, liver-related mortality, and hepatitis recurrence after liver transplantation. Treatment during compensated cirrhosis proved to be most cost-effective versus treatment after decompensation or a no-treatment strategy. Headache (54%), irritability (38%), fatigue (34%), and nausea (30%) were the most common adverse events in compensated patients, while anorexia (100%), fatigue (59%), neutropenia (53%), and thrombocytopenia (50%) were most common in decompensated patients. CONCLUSIONS: Anti-HCV treatment in cirrhoticpatients was less effective than in noncirrhotic patients. Viral eradication reduced the risk of liver complications and improved survival in noncirrhotics. Based on effectiveness and tolerability data, therapy has a significant effect in patients with compensated cirrhosis, while decompensated patients need to weigh the risks versus benefits of treatment.
Authors: Jordan J Feld; Raoel Maan; Stefan Zeuzem; Alexander Kuo; David R Nelson; Adrian M Di Bisceglie; Michael P Manns; Ken Sherman; Lynn M Frazier; Richard Sterling; Mark Mailliard; Monica Schmidt; Lucy Akushevich; Monika Vainorius; Michael W Fried Journal: Clin Infect Dis Date: 2016-06-19 Impact factor: 9.079
Authors: Joseph S Doyle; Esther Aspinall; Danny Liew; Alexander J Thompson; Margaret E Hellard Journal: Br J Clin Pharmacol Date: 2013-04 Impact factor: 4.335