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J Hepatol. 2001 Dec;35(6):749-55.

Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B.

Author information

1
University of North Carolina, CB# 7080, Room 708, Burnett-Womack Building, Chapel Hill, NC 27599, USA.

Erratum in

  • J Hepatol 2002 May;36(5):714. Burkhardt ER [corrected to Burchardt ER].

Abstract

BACKGROUND:

Activation of hepatic stellate cells is the earliest step in fibrogenesis. Alpha-smooth muscle actin (alpha-SMA), expressed by activated hepatic stellate cells, and C-terminal procollagen alpha1(III) propeptide (PIIICP) are early markers of fibrogenesis and should precede fibrosis.

AIM:

Determine if suppression of hepatitis B virus replication with lamivudine would decrease fibrogenesis as measured by immunohistochemical markers.

METHODS:

Paired 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.

RESULTS:

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). PIIICP was similarly decreased after lamivudine. Among subjects whose Histologic Activity Index fibrosis score was unchanged or worsened, the mean change in alpha-SMA expression was significantly decreased in the lamivudine group compared with placebo.

CONCLUSIONS:

Lamivudine decreased markers of hepatic stellate cell activation and collagen synthesis. Immunohistochemical techniques are sensitive for assessing fibrogenesis and will be useful in trials of antiviral and antifibrotic agents.

PMID:
11738102
DOI:
10.1016/s0168-8278(01)00218-5
[Indexed for MEDLINE]

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