Histological outcome during long-term lamivudine therapy
Histological outcome during long-term lamivudine therapy
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DOI：
10.1053/gast.2003.50013
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发表时间：
2003-01-01
期刊：
影响因子：
29.4
通讯作者：
Schiff, ER
中科院分区：
文献类型：
--
作者：
Dienstag, JL;Goldin, RD;Schiff, ER
背景与目的：拉米夫定治疗慢性B型肝炎一年后，组织学改善。我们的目的是评估长期治疗的组织学影响。研究方法：随机拉米夫定治疗1年前后和进一步开放标签治疗2年后的63例患者的3组肝活检组织被分配为组织学活动指数评分，编号为。结果如下：在第1年结束时，36/63例（57%）显示出大于或等于2分的改善，24/63例（38%）的坏死性炎症活动没有变化;在拉米夫定治疗2年后，38/63例（60%）保持稳定，12/63例（19%）继续改善。有和无YMDD（酪氨酸、甲硫氨酸、天冬氨酸、天冬氨酸）变异的患者中发生恶化的比例相似。在所有3年的拉米夫定治疗后，35/63（56%）的患者表现出改善，21/63（33%）没有变化，7/63（11%）恶化。与携带YMDD变异的患者相比，不携带YMDD变异的患者更有可能改善（17/22 [77%] vs. 18/41 [44%]），恶化的可能性较小（1/22 [5%] vs. 6/41 [15%]）。YMDD变异>2年的患者最不可能改善（8/22 [36%]）。12/19例（63%）的桥接纤维化改善≥ 1级，8/11例（73%）的肝硬化改善（评分4至≤ 3）。仅1/52例[2%]显示进展为肝硬化，3/34例（9%）显示进展为桥接纤维化（均为YMDD变体）。结论：3年拉米夫定治疗减少了大多数患者的坏死性炎症活动，逆转了纤维化（包括肝硬化）。YMDD变异体的出现减弱了组织学反应;因此，持续时间延长的YMDD变异体可能需要额外的治疗来维持治疗的组织学获益。
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 I 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 greater than or equal to2 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 greater than or equal to1 level in 12/19 (63%), and cirrhosis improved (score of 4 to less than or equal to3) 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.