Wei Wei, Wu Qinmei, Zhou Jialing, Kong Yuanyuan, You Hong
Clinical Epidemiology and Evidence-based Medicine Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-An Road, Beijing 100050, China.
National Clinical Research Center for Digestive Diseases, 95 Yong-An Road, Beijing 100050, China.
Int J Environ Res Public Health. 2015 Aug 21;12(8):10039-55. doi: 10.3390/ijerph120810039.
The clinical efficacy of nucleos(t)ide analogues (NAs) combined with interferon (IFN) therapy vs. NAs monotherapy for chronic hepatitis B (CHB) remains inconclusive. The aim of this meta-analysis was to determine whether the NAs plus IFN regimen offers synergistic efficacy that justifies the cost and burden of such a combination therapy in CHB patients.
Related publications covering the period of 1966 to July 2014 were identified through searching MEDLINE, EMBASE, Cochrane library, Chinese Biomedical Literature Database, WANFANG, and CNKI database. A total of 17 studies were enrolled, including 6 in English and 11 in Chinese. Then, we established a final list of studies for the meta-analysis by systematically grading the quality and eligibility of the identified individual studies. We used hepatitis B antigen (HBeAg) loss, HBV-DNA undetectable rate, HBeAg seroconversion, hepatitis B surface antigen (HBsAg) loss, HBsAg seroconversion, and histological score at the end of treatment for efficacy evaluation. A quantitative meta-analysis (Review Manager, Version 5.1.0) was performed to assess the differences between NAs and IFN combination therapy and NAs monotherapy.
Our analysis demonstrated that HBeAg loss (RR = 1.73, 95% CI = 1.32-2.26, p < 0.001), HBV-DNA undetectable rate (RR = 1.58, 95% CI = 1.22-2.04, p < 0.001), HBeAg seroconversion (RR = 1.68, 95% CI = 1.36-2.07, p < 0.001), and HBsAg loss (RR = 2.51, 95% CI = 1.32-4.75, p < 0.001) in the combination therapy group were significantly higher than those in the monotherapy group. However, there were no significant differences in HBsAg seroconversion (RR = 4.25, 95% CI = 0.62-29.13, p = 0.14), sustained virological response rates, and biochemical response rates observed between the two groups. The results showed that the combination therapy group had more improved HBV histology than the NAs monotherapy group (RR = 1.14, 95% CI = 0.93-1.39, p = 0.22).
NAs and IFN or Peg-IFN combination therapy had a better efficacy in terms of HBeAg loss, HBV-DNA undetectable rate, HBeAg seroconversion, and HBsAg loss, compared to the NA monotherapy group at the end of treatment; however, there was no significant difference in HBsAg seroconversion between the two regimens.
核苷（酸）类似物（NAs）联合干扰素（IFN）治疗与NAs单药治疗慢性乙型肝炎（CHB）的临床疗效仍无定论。本荟萃分析的目的是确定NAs加IFN方案是否具有协同疗效，从而证明这种联合治疗在CHB患者中的成本和负担是合理的。
通过检索MEDLINE、EMBASE、Cochrane图书馆、中国生物医学文献数据库、万方和知网数据库，确定了1966年至2014年7月期间的相关出版物。共纳入17项研究，其中英文研究6项，中文研究11项。然后，我们通过系统评估所确定的个体研究的质量和合格性，建立了用于荟萃分析的最终研究列表。我们采用治疗结束时的乙肝抗原（HBeAg）消失、HBV-DNA不可检测率、HBeAg血清学转换、乙肝表面抗原（HBsAg）消失、HBsAg血清学转换和组织学评分进行疗效评估。采用定量荟萃分析（Review Manager，版本5.1.0）评估NAs与IFN联合治疗和NAs单药治疗之间的差异。
我们的分析表明，联合治疗组的HBeAg消失（RR = 1.73，95%CI = 1.32 - 2.26，p < 0.001）、HBV-DNA不可检测率（RR = 1.58，95%CI = 1.22 - 2.04，p < 0.001）、HBeAg血清学转换（RR = 1.68，95%CI = 1.36 - 2.07，p < 0.001）和HBsAg消失（RR = 2.51，95%CI = 1.32 - 4.75，p < 0.001）显著高于单药治疗组。然而，两组之间在HBsAg血清学转换（RR = 4.25，95%CI = 0.62 - 29.13，p = 0.14）、持续病毒学应答率和生化应答率方面无显著差异。结果显示，联合治疗组的HBV组织学改善情况优于NAs单药治疗组（RR = 1.14，95%CI = 0.93 - 1.39，p = 0.22）。
与治疗结束时的NAs单药治疗组相比，NAs与IFN或聚乙二醇干扰素联合治疗在HBeAg消失、HBV-DNA不可检测率、HBeAg血清学转换和HBsAg消失方面疗效更好；然而，两种治疗方案在HBsAg血清学转换方面无显著差异。
