长期拉米夫丁治疗对肝脏组织学效应的研究

liver411

VIRAL HEPATITIS B- Histological outcome during long-term lamivudine therapy
病毒性乙肝---长期拉米夫丁治疗对肝脏组织学效应的研究
J. L. Dienstag (1) , R. D. Goldin (2) , E. J. Heathcote (3), H. W. L. Hann (4) , M. Woessner (5) , S. L. Stephenson (5), S.Gardner (5), D. Fraser Gray (5), , E. R. Schiff (6)

(1) Gastrointestinal Unit (Medical Services), Massachusetts General Hospital and the Department of Medicine, Harvard Medical School, Boston, Massachusetts;
(2) Imperial College School of Medicine, St. Mary's Hospital, Paddington, London, England;
(3) University Health Network, Toronto Western Hospital, Toronto, Canada;
(4) Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania;
(5) GlaxoSmithKline Research and Development, Greenford, United Kingdom and Research Triangle Park, North Carolina;
(6) The Liver Center, University of Miami Medical Center, Miami, Florida

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.
背景和目标: 对慢性乙肝实行一年拉米夫丁治疗后会提高肝脏组织学. 我们的目的是观察长期拉米使用对于组织学的影响.

方法: 制定三次肝脏穿刺, 63名病人, 任选, 1年前, 一年后, 两年后(开封)拉米夫丁治疗. 三次肝穿的纪录结果是编码保密的.

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).
结果: 一年后, 36/63人 (57%) 显示2位肝穿点数进步, 24/63人 (38%)没有坏死发炎性活动; 再加2年拉米夫丁治疗, 38/63 (60%) 持续稳定, 12/63人持续进步. 不好的人数在产生YMDD, 或不产YMDD变异型中比例大约相等. 3年拉米夫丁治疗后, 35/63人 (56%) 显示进步, 21/63人 (33%) 没变化, 7/63人 (11%) 恶化. 这些不包括, YMDD变异曾改善(17/22[77%] 对比 18/41 [44%]), 不曾恶化 (1/22[5%] 对比 6/41 [15%]). 病人染有YMDD2年以上最不容易提高进步(8/22 [36%]). 网状褡裢(桥连)纤维化提高进步了一级, 肝硬化提高 (4-3分), 8/11人 (73%). 只有 1/52 [2%]) 显示硬化恶化, 3/34人 (9%) 恶化成桥链纤维化 (全部为YMDD变异病人)

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. (Gastroenterology 124, 105-117, 2003).
结论: 3年拉米夫丁治疗对于大部分病人来说减低坏死性肝炎活动, 逆转纤维化 (包括硬化). YMDD的产生使组织学反应迟钝, 所以, 对于长期YMDD变异型, 延长治疗以维持从治疗中获得的组织学改善.


***********


拉米夫丁事实上算比较安全, 副作用小的药物, 除去抗药变异是一大问题. 就药物本身来说它对(并不是转阴治愈神药, 那也不是唯一治疗目的)提高肝脏组织学, 减少坏死刑活动炎症, 甚至提高现在标志肝病病人生命健康指数的凝血, 黄疸, 肌酸, 还有白蛋白, 纤维化, 硬化活检分数级别(有文章日后有机会再登出来)都很有效益. 目前的关键是如何治疗变异将提高的组织学保持下去. (411011103)