Hepatitis C Response to Interferon May Improve Survival

Joe Barber Jr, PhD

December 27, 2012

Among patients with chronic hepatitis C virus (HCV) infection and advanced hepatic fibrosis, those who achieve a sustained virological response (SVR) to interferon-based therapy are much less likely to die from any cause, according to the findings of a multicenter, long-term follow-up study.

Adriaan J. van der Meer, MD, from Erasmus MC University Medical Center in Rotterdam, the Netherlands, and colleagues published their findings in the December 26 issue of JAMA.

The authors note that despite its importance, the relationship between SVR and survival remains to be clarified. "Although SVR has long-term durability, data on the relationship with improved survival to support its use as a surrogate end point of antiviral therapy is scarce," the authors write. "Demonstrating direct clinical benefits would better justify the use of intensive and costly antiviral therapy, such as expensive direct antiviral agents, which improve treatment efficacy when added to pegylated interferon and ribavirin for many patients with chronic HCV genotype infection."

In the study, after excluding 8 patients who were lost to follow-up, 3 patients who developed hepatocellular carcinoma, and 5 patients who developed liver failure within 24 weeks after the end of treatment, the authors included 530 patients with chronic HCV infection and histological proof of advanced fibrosis or cirrhosis (Ishak score, 4 - 6) who received interferon-based therapy between 1990 and 2003. Patients who achieved an SVR had a much lower-all cause mortality rate than those who did not achieve an SVR (8.9% [95% confidence interval (CI), 3.3% - 14.5%] vs 26.0% [95% CI, 20.2% - 28.4%]; P < .001).

Multivariate Cox regression analysis was performed with adjustment for age, sex, SVR, and all variables with P values of less than .20 in univariate analyses. SVR was associated with much lower risks for all-cause mortality (hazard ratio [HR], 0.26; 95% CI, 0.14 - 0.49; P < .001), liver-related mortality or transplantation (HR, 0.06; 95% CI, 0.02 - 0.19; P < .001), hepatocellular carcinoma (HR, 0.19; 95% CI, 0.08 - 0.44; P < .001), and liver failure (HR, 0.07; 95% CI, 0.03 - 0.20; P < .001).

HCV genotype 3 (HR, 2.08; 95% CI, 1.18 - 3.66; P = .01), diabetes mellitus (HR, 1.76; 95% CI, 1.02 - 3.01; P = .04), a history of severe alcohol use (HR, 2.20; 95% CI, 1.32 - 3.67; P = .002), and an Ishak fibrosis score of 6 (HR, 1.87; 95% CI, 1.02 - 3.45; P = .04) were associated with increased risks for all-cause mortality.

The limitations of the study include its retrospective nature, the potential inclusion of a healthier-than-expected cohort, and the likely difference in follow-up duration between patients who achieved an SVR and those who did not.

"In conclusion, our study indicates that SVR was associated with improved overall survival in patients with chronic HCV infection and advanced hepatic fibrosis," the authors write.

Study Findings May Influence Policy Decisions

Joseph K. Lim, MD, director of the Yale Viral Hepatitis Program, Yale University School of Medicine in New Haven, Connecticut, who was not involved in the study, noted that the findings will be of key importance to policy makers. "The primary finding of a 4-fold decrease in all-cause mortality is of vital importance in proving clinical effectiveness of HCV therapy in real-life patients with advanced liver disease, based not only on achieving surrogate outcomes such as SVR but on hard clinical outcomes of all-cause and liver-related mortality," Dr. Lim told Medscape Medical News by email.

"Simply put, antiviral therapy resulting in SVR saves lives. This will be of keen interest to policy makers such as the US Preventive Services Task Force, health economists, and third-party payers as they consider implementation of the recent [Centers for Disease Control and Prevention] recommendations to screen all US adults born between 1945 and 1965 and those with known risk factors for hepatitis C infection."

This study was supported by the Foundation for Liver and Gastrointestinal Research, Rotterdam, the Netherlands. Dr. van der Meer has disclosed no relevant financial relationships. Full conflict-of-interest information is available in the article. Dr. Lim has reported that his institution has research contracts with Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, Genentech, Gilead, GlaxoSmithKline, Janssen/Johnson and Johnson, and Vertex, and he received consulting fees/honoraria from Bristol-Myers Squibb, Gilead, Merck, and Vertex.

JAMA. 2012;308:2584-2593. Abstract