We investigated the effects of polymorphisms in
interleukin (IL)-10 and
tumor necrosis factor (
TNF)-alpha on the natural course of hepatitis C virus (HCV)
infection in a community-based population in Japan. A total of 460 anti-HCV antibody seropositive individuals were classified into two groups, those who were positive or negative for HCV
RNA. In HCV
RNA-positive individuals with at least four annual
alanine aminotransferase (ALT) measurements taken between 1993 and 2003, 74 exhibited persistently normal ALT levels, while 211 had one or more elevated ALT level tests. We examined the relationships between polymorphisms in the genes encoding
IL-10 (-1082, -819, -592) or
TNF-alpha (-308, -238) and HCV clearance, ALT abnormalities, or serum level of
type IV collagen 7S, a marker of hepatic
fibrosis. These polymorphisms were equally distributed among the patient subgroups with differential HCV
RNA clearances or ALT abnormalities. Serum levels of
type IV collagen 7S, however, were significantly higher in individuals with an A at position -238 or -308 in the
TNF-alpha gene promoter than in individuals lacking these polymorphisms. We conclude that, while the relationships between inherited variations in
IL-10 or
TNF-alpha expression are not associated with alterations in HCV clearance or ALT levels,
TNF-alpha polymorphisms may be associated with hepatic
fibrosis.