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Gastroenterology. 2003 Jan;124(1):105-17.

Histological outcome during long-term lamivudine therapy.

Author information

1
Gastrointestinal Unit (Medical Services), Massachusetts General Hospital, Boston, MA 02114, USA. JDienstag@partners.org

Abstract

BACKGROUND & AIMS:

One year of lamivudine for chronic hepatitis B results in histologic improvement. We aimed to assess the histological impact of longer-term treatment.

METHODS:

Sets of 3 liver biopsies, from 63 patients before and after 1 year of randomized lamivudine treatment and after 2 years of further open-label treatment, were assigned Histologic Activity Index scores under code.

RESULTS:

At the end of year 1, 36/63 (57%) showed > or =2 point improvement and 24/63 (38%) no change in necroinflammatory activity; after 2 additional years of lamivudine, 38/63 (60%) remained stable and 12/63 (19%) continued to improve. Worsening occurred in similar proportions of patients with and without YMDD (tyrosine, methionine, aspartate, aspartate) variants. After all 3 years of lamivudine treatment, 35/63 (56%) of patients showed improvement, 21/63 (33%) no change, and 7/63 (11%) worsening. Those without, compared with those with, YMDD variants were more likely to improve (17/22 [77%] vs. 18/41 [44%]) and less likely to deteriorate (1/22 [5%] vs. 6/41 [15%]). Patients with YMDD variants for >2 years were least likely to improve (8/22 [36%]). Bridging fibrosis improved by > or =1 level in 12/19 (63%), and cirrhosis improved (score of 4 to < or =3) in 8/11 (73%). Only 1/52 [2%]) showed progression to cirrhosis, and 3/34 (9%) showed progression to bridging fibrosis (all with YMDD variants).

CONCLUSIONS:

Three years of lamivudine therapy reduces necroinflammatory activity and reverses fibrosis (including cirrhosis) in most patients. The emergence of YMDD variants blunts histologic responses; therefore, extended-duration YMDD variants may require additional therapies to maintain the histological benefit of treatment.

PMID:
12512035
DOI:
10.1053/gast.2003.50013
[Indexed for MEDLINE]

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