RESUMO
Activation of hepatic stellate cells is the earliest step in fibrogeneesis. Alpha-smooth muscle acting [alpha-SMA], expressed by activated hepatic sallate cells, and C-terminal procollagen alpha [III] propeptide [PIIICP] are early markers of fibrogenesis and should precede fibrosis. ASD: Determine if suppression of hepatitis B virus replication with lamivudine would decrease fibrogenesis as measured by immunohistochemical markers. Paried liver biopsies from patients with hepatitis B before and after therapy with lamivudine [n=47] or placebo [n=33] were studied. Alpha-SMA and PIIICP were detected in paraffin-embedded tissue by immunohistochemistry and quantified in a blinded manner by video imaging analysis. Liver biopsies from patients treated with lamivudine showed a significant decrease in alpha-SMA expression [1.06 +/- 0.23 vs. 0.58 +/- 0.11, pre vs. post, P< 0.05]. Placebo recipients had increased levels of alpha -SMA 0.82 +/- 0.14 vs. 1.32 +/- 0.21, P< 0.05]. PIICP was similarly decreased after lamivudine. Among subjects whose Histological Activity Index fibrosis score was unchanged or worsened, the mean changes in alpha-SMA expression was significantly decreased in the lamivudine group compared with placebo. Lamivudine decreased markers of hepatic satellite cell activation and collagen synthesis. Immunohistochemical techniques are sensitive for assessing fibro-genesis and will be useful in trials of antiviral and antifibrotic agents