Chan Henry Lik-Yuen, Wong Vincent Wai-Sun, Hui Alex Yui, Tsang Steven Woon-Choy, Chan Joyce Lai-Yee, Chan Hoi-Yui, Wong Grace Lai-Hung, Sung Joseph Jao-Yiu
Department of Medicine and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
Antivir Ther. 2006;11(4):465-71.
Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B is difficult to treat and there is little long-term data for lamivudine treatment of severe acute exacerbation. We report a prospective, consecutive cohort of severe acute exacerbation of HBeAg-negative chronic hepatitis B patients treated by lamivudine between 1999 and 2004. All patients had respectively increased alanine aminotransferase and serum bilirubin to at least 10 and 2 times the upper limit of laboratory normal. Thirty-two patients were treated with lamivudine for 130 +/- 58 (range 48-217) weeks. Five patients had evidence of virological breakthrough (HBV DNA >10,000 copies/ml) during lamivudine treatment. The cumulative probability of maintained response without any virological breakthrough was 94% (95% confidence interval [CI], 86-100%) at year 1, 94% (95% CI, 82-100%) at year 2 and 71% (95% CI, 41-100%) at year 3. At the last follow-up visit, 31 (97%) lamivudine patients had HBV DNA <10,000 copies/ml. The prevalence of lamivudine resistance mutation was 1 in 32 patients (3%; 95% CI, 0-9%) at year 1, 1 in 17 patients (6%; 95% CI, 0-17%) at year 2, 1 in 9 patients (11%, 95% CI, 0-32%) at year 3 and 1 in 4 patients (25%; 95% CI, 0-67%) at year 4 of lamivudine treatment. In conclusion, extended lamivudine treatment is associated with a high maintained virological response and a low rate of drug resistance in severe acute exacerbation of HBeAg-negative chronic hepatitis B.
乙肝e抗原（HBeAg）阴性的慢性乙型肝炎难以治疗，且关于拉米夫定治疗严重急性加重期的长期数据很少。我们报告了1999年至2004年间接受拉米夫定治疗的HBeAg阴性慢性乙型肝炎严重急性加重期患者的一项前瞻性连续队列研究。所有患者的丙氨酸转氨酶和血清胆红素分别至少升高至实验室正常上限的10倍和2倍。32例患者接受拉米夫定治疗130±58（范围48 - 217）周。5例患者在拉米夫定治疗期间出现病毒学突破（HBV DNA>10,000拷贝/ml）。1年时无任何病毒学突破的持续应答累积概率为94%（95%置信区间[CI]，86 - 100%），2年时为94%（95% CI，82 - 100%），3年时为71%（95% CI，41 - 100%）。在最后一次随访时，31例（97%）拉米夫定治疗患者的HBV DNA<10,000拷贝/ml。拉米夫定耐药突变的发生率在拉米夫定治疗1年时为32例中的1例（3%；95% CI，0 - 9%），2年时为17例中的1例（6%；95% CI，0 - 17%），3年时为9例中的1例（11%，95% CI，0 - 32%），4年时为4例中的1例（25%；95% CI，0 - 67%）。总之，在HBeAg阴性慢性乙型肝炎严重急性加重期，延长拉米夫定治疗与高持续病毒学应答率和低耐药率相关。
