日大医学雑誌

C 型肝炎ウイルスと肝細胞癌の missing link

総説

著者

江  角  真理子
日本大学医学部病理学講座

要旨

Hepatitis C virus (HCV) infection causes chronic hepatitis in 70-80% of cases and eventually leads to cirrhosis andhepatocellular carcinoma. HCV induces innate and adaptive immune response, but persistent infection is establishedprobably due to 1) the immune selection of escape mutants and 2) modulation of innate and adaptive immune response byHCV proteins. HCV infection induces proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and cytotoxicT lymphocyte (CTL) activity, followed by liver injury. TNF-α, especially, has a central role in the pathophysiology ofchronic hepatitis C: TNF-α levels correlate with the necro-inflammatory score and the progression of fibrosis. A possiblemechanism of the progression of hepatocellular carcinoma is discussed with reference to a new finding that NF-κBactivated by TNF-α functions as a tumor promoter in inflammation-associated cancer. Potential therapeutic strategiesagainst chronic hepatitis C are suggested based on the pathogenesis.

keyword

Hepatitis C virus, chronic hepatitis, hepatocellular carcinoma, IFN-α, TNF-α
C 型肝炎ウイルス,慢性肝炎,肝細胞癌,インターフェロン-α, TNF-α