Antiviral response of HCV genotype 1 to consensus interferon and ribavirin versus pegylated interferon and ribavirin.

Achieving an antiviral response at a reasonable cost is a challenge in the treatment of patients with chronic hepatitis C. A previous study indicated that consensus interferon with ribavirin had promising activity against hepatitis C virus (HCV) genotype 1. The objective of this study was to determine the virologic response with consensus interferon or pegylated interferon alpha-2b plus weight-ribavirin in patients chronically infected with HCV genotype 1. Intention-to-treat analysis showed response in 37% and 41% of subjects treated with consensus interferon/ribavirin or pegylated interferon/ribavirin, respectively, with response rates of 42% and 44% observed in analysis of the per-protocol population, not a significant difference. Tolerability of the two treatment regimens was similar. In conclusion, both treatment regimens were safe and gave a similar antiviral response. It is possible that if consensus interferon is administered daily rather than three times weekly, eradication of HCV could be achieved in a larger proportion of patients infected with HCV genotype 1.

Liver biopsy in cirrhotic patients.

Liver biopsy remains an important tool for the evaluation of patients with hepatic disease. However, clinicians utilize a variety of biopsy techniques including automated cutting needle devices, manual cutting needles, and aspiration needles. Using a large study cohort of patients with advanced fibrosis/cirrhosis we sought to evaluate practices and outcomes of the biopsy technique used by study investigators across the United States. All biopsy samples were from patients with suspected advanced fibrosis or cirrhosis because of hepatitis C virus (HCV) infection. Individual study investigators were permitted to use any biopsy technique. Biopsy specimens were centrally evaluated for tissue adequacy and fragmentation, and were histologically scored using accepted criteria. We evaluated a total of 923 liver biopsy specimens from 502 patients performed at 62 clinical sites. The average duration of HCV infection was 27.9 +/- 0.46 yr. Automated cutting needles were significantly more likely to provide adequate specimens for evaluation than aspiration needles (P < 0.005). Automated cutting needles produced significantly longer biopsies than other techniques (P < 0.05), except for a limited number of cases in which a surgical wedge biopsy was obtained. Tissue fragmentation was observed in 39.2% of liver biopsies obtained using an aspiration technique, but in only 4.7% of samples collected using an automated cutting needle (P < 0.001). We conclude that automated cutting needles provide superior liver biopsy specimens compared with aspiration techniques in subjects with advanced fibrosis/cirrhosis. No specific safety issues attributable to a particular biopsy method were identified.

Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-gamma1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis.

UNLABELLED: Interferon-gamma1b (IFN-gamma1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-gamma1b 100 microg (group 1, n=169), IFN-gamma1b 200 microg (group 2, n=157), or placebo (group 3, n=162) 3 times a week for 48 weeks. Most patients (83.6%) had cirrhosis at baseline (Ishak score=5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1%, 12.4%, and 16% of patients in groups 1, 2, and 3, respectively; P>0.05). Analysis of IFN-gamma-inducible biomarkers revealed that interferon-inducible T cell-alpha chemoattractant (ITAC), an IFN-gamma-inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-gamma1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis. CONCLUSION: IFN-gamma1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-gamma1b.