Details

Autor(en) / Beteiligte

• Farci, Patrizia
• Wollenberg, Kurt
• Diaz, Giacomo
• Engle, Ronald E
• Lai, Maria Eliana
• Klenerman, Paul
• Purcell, Robert H
• Pybus, Oliver G
• Alter, Harvey J

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2012-09, Vol.109 (36), p.14562-14567

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.