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 language | English |
|---|---|
| Pages (from-to) | 105-117 |
| Number of pages | 13 |
| Journal | Gastroenterology |
| Volume | 124 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2003 |
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ASJC Scopus subject areas
- Gastroenterology
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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 journal › Article
}
TY - JOUR
T1 - Histological outcome during long-term lamivudine therapy
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
PY - 2003/1/1
Y1 - 2003/1/1
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.
UR - http://www.scopus.com/inward/record.url?scp=0037221907&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037221907&partnerID=8YFLogxK
U2 - 10.1053/gast.2003.50013
DO - 10.1053/gast.2003.50013
M3 - Article
C2 - 12512035
AN - SCOPUS:0037221907
VL - 124
SP - 105
EP - 117
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 1
ER -