Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis.

Journal article

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis.

Authors: Farci, P; Wollenberg, K; Diaz, G; Engle, R; Lai, M

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 109
• Issue: 36
• Pages: 14562-14567
• Publication date: 2012-09-01
• DOI: 10.1073/pnas.1210592109
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Statistics, Nonparametric; Cloning, Molecular; Alanine Transaminase; Hepatitis C; Reverse Transcriptase Polymerase Chain Reaction; Disease Progression; Base Sequence; Molecular Sequence Data; Chemokine CCL4; Hepacivirus; Evolution, Molecular; RNA, Viral; Interferon-gamma; Chemokines; Sequence Analysis, DNA; Liver Cirrhosis