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恩替卡韦与基于拉米夫定的疗法治疗慢性乙型肝炎患者的组织学结果。

Histological outcome for chronic hepatitis B patients treated with entecavir vs lamivudine-based therapy.

作者信息

Wang Jia-Li, Du Xin-Fang, Chen Shao-Long, Yu Yi-Qi, Wang Jing, Hu Xi-Qi, Shao Ling-Yun, Chen Jia-Zhen, Weng Xin-Hua, Zhang Wen-Hong

机构信息

Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.

出版信息

World J Gastroenterol. 2015 Aug 28;21(32):9598-606. doi: 10.3748/wjg.v21.i32.9598.

Abstract

AIM

To compare the histological outcome of chronic hepatitis B (CHB) patients treated with entecavir (ETV) or lamivudine (LAM)-based therapy.

METHODS

We conducted a retrospective analysis of data from 42 CHB patients with advanced fibrosis (baseline Ishak score ≥ 2) or cirrhosis who were treated with ETV or LAM-based therapy in Beilun People's Hospital, Ningbo between January 2005 and May 2012. The patients enrolled were more than 16 years of age and underwent a minimum of 12 mo of antiviral therapy. We collected data on the baseline characteristics of each patient and obtained paired liver biopsies pre- and post-treatment. The Knodell scoring system and Ishak fibrosis scores were used to evaluate each example. An improvement or worsening of necroinflammation was defined as ≥ 2-point change in the Knodell inflammatory score. The progression or regression of fibrosis was defined as ≥ 1-point change in the Ishak fibrosis score. The continuous variables were compared using t-test or Mann-Whitney test, and the binary variables were compared using χ(2) test or Fisher's exact test. The results of paired liver biopsies were compared with a Wilcoxon signed rank test.

RESULTS

Nineteen patients were treated with ETV and 23 patients were treated with LAM therapy for a mean duration of 39 and 42 mo, respectively. After long-term antiviral treatment, 94.74% (18/19) of the patients in the ETV arm and 95.65% (22/23) in the LAM arm achieved an HBV DNA level less than 1000 IU/mL. The majority of the patients (94.74% in the ETV arm and 73.91% in the LAM arm) had normalized ALT levels. The median Knodell necroinflammatory score decreased from 11 to 0 in the patients receiving ETV, and the median Knodell score decreased from 9 to 3 in the patients receiving LAM (P = 0.0002 and < 0.0001, respectively). The median Ishak fibrosis score showed a 1-point reduction in ETV-treated patients and a 2-point reduction in LAM-treated patients (P = 0.0019 and 0.0205, respectively). The patients receiving ETV showed a more significant improvement in necroinflammation than the LAM-treated patients (P = 0.0003). However, there was no significant difference in fibrotic improvement between the two arms. Furthermore, two patients in each arm achieved a fibrosis score of 0 post-treatment, which indicates a full reversion of fibrosis after antiviral therapy.

CONCLUSION

CHB patients with advanced fibrosis or cirrhosis benefit from antiviral treatment. ETV is superior to LAM therapy in improving necroinflammatory but not fibrotic outcome.

摘要

目的

比较接受恩替卡韦(ETV)或基于拉米夫定(LAM)治疗的慢性乙型肝炎(CHB)患者的组织学结果。

方法

我们对2005年1月至2012年5月期间在宁波北仑区人民医院接受ETV或基于LAM治疗的42例晚期纤维化(基线Ishak评分≥2)或肝硬化的CHB患者的数据进行了回顾性分析。纳入的患者年龄超过16岁,且接受了至少12个月的抗病毒治疗。我们收集了每位患者的基线特征数据,并在治疗前后获取配对的肝脏活检样本。使用Knodell评分系统和Ishak纤维化评分对每个样本进行评估。坏死性炎症的改善或恶化定义为Knodell炎症评分变化≥2分。纤维化的进展或消退定义为Ishak纤维化评分变化≥1分。连续变量采用t检验或Mann-Whitney检验进行比较,二元变量采用χ(2)检验或Fisher精确检验进行比较。配对肝脏活检的结果采用Wilcoxon符号秩检验进行比较。

结果

19例患者接受ETV治疗,23例患者接受LAM治疗,平均治疗时间分别为39个月和42个月。经过长期抗病毒治疗后,ETV组94.74%(18/19)的患者和LAM组95.65%(22/23)的患者HBV DNA水平低于1000 IU/mL。大多数患者(ETV组为94.74%,LAM组为73.91%)的ALT水平恢复正常。接受ETV治疗的患者Knodell坏死性炎症评分中位数从11降至0,接受LAM治疗的患者Knodell评分中位数从9降至3(分别为P = 0.0002和<0.0001)。ETV治疗患者Ishak纤维化评分中位数降低1分,LAM治疗患者降低2分(分别为P = 0.0019和0.0205)。接受ETV治疗的患者在坏死性炎症方面的改善比接受LAM治疗的患者更显著(P = 0.0003)。然而,两组在纤维化改善方面没有显著差异。此外,每组各有2例患者在治疗后纤维化评分为0,这表明抗病毒治疗后纤维化完全逆转。

结论

晚期纤维化或肝硬化的CHB患者可从抗病毒治疗中获益。在改善坏死性炎症方面,ETV优于LAM治疗,但在纤维化结果方面并非如此。

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