Histological outcome during long-term lamivudine therapy

Jules L. Dienstag, Robert D. Goldin, E. Jenny Heathcote, H. W L Hann, Mary Woessner, Sally L. Stephenson, Stephen Gardner, D. Fraser Gray, Eugene R Schiff

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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 ≥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 ≥1 level in 12/19 (63%), and cirrhosis improved (score of 4 to ≤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.

Original languageEnglish
Pages (from-to)105-117
Number of pages13
JournalGastroenterology
Volume124
Issue number1
DOIs
StatePublished - Jan 1 2003

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Lamivudine
Fibrosis
Aspartic Acid
Therapeutics
Chronic Hepatitis B
Methionine
Tyrosine
Biopsy
Liver

ASJC Scopus subject areas

  • Gastroenterology

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Dienstag, J. L., Goldin, R. D., Heathcote, E. J., Hann, H. W. L., Woessner, M., Stephenson, S. L., ... Schiff, E. R. (2003). Histological outcome during long-term lamivudine therapy. Gastroenterology, 124(1), 105-117. https://doi.org/10.1053/gast.2003.50013

Histological outcome during long-term lamivudine therapy. / Dienstag, Jules L.; Goldin, Robert D.; Heathcote, E. Jenny; Hann, H. W L; Woessner, Mary; Stephenson, Sally L.; Gardner, Stephen; Gray, D. Fraser; Schiff, Eugene R.

In: Gastroenterology, Vol. 124, No. 1, 01.01.2003, p. 105-117.

Research output: Contribution to journalArticle

Dienstag, JL, Goldin, RD, Heathcote, EJ, Hann, HWL, Woessner, M, Stephenson, SL, Gardner, S, Gray, DF & Schiff, ER 2003, 'Histological outcome during long-term lamivudine therapy', Gastroenterology, vol. 124, no. 1, pp. 105-117. https://doi.org/10.1053/gast.2003.50013
Dienstag JL, Goldin RD, Heathcote EJ, Hann HWL, Woessner M, Stephenson SL et al. Histological outcome during long-term lamivudine therapy. Gastroenterology. 2003 Jan 1;124(1):105-117. https://doi.org/10.1053/gast.2003.50013
Dienstag, Jules L. ; Goldin, Robert D. ; Heathcote, E. Jenny ; Hann, H. W L ; Woessner, Mary ; Stephenson, Sally L. ; Gardner, Stephen ; Gray, D. Fraser ; Schiff, Eugene R. / Histological outcome during long-term lamivudine therapy. In: Gastroenterology. 2003 ; Vol. 124, No. 1. pp. 105-117.
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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 ≥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 ≥1 level in 12/19 (63{\%}), and cirrhosis improved (score of 4 to ≤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.",
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AU - Dienstag, Jules L.

AU - Goldin, Robert D.

AU - Heathcote, E. Jenny

AU - Hann, H. W L

AU - Woessner, Mary

AU - Stephenson, Sally L.

AU - Gardner, Stephen

AU - Gray, D. Fraser

AU - Schiff, Eugene R

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N2 - 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 ≥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 ≥1 level in 12/19 (63%), and cirrhosis improved (score of 4 to ≤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.

AB - 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 ≥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 ≥1 level in 12/19 (63%), and cirrhosis improved (score of 4 to ≤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.

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