Objectives

Chronic hepatitis B (CHB) is a major global health problem caused by hepatitis B virus (HBV) infection, and can put patients at high risk of death from cirrhosis and liver cancer. However, CHB can be treated with nucleos(t)ide analogues. We aimed to evaluate the effectiveness and safety of nucleos(t)ide analogues for the treatment of CHB patients.

Methods

A systematic literature search was performed. Direct comparison meta-analyses and network meta-analysis (NMA) were carried out.

Results

Thirty-six randomized controlled trials (RCTs) met inclusion criteria. Compared with placebo, the nucleos(t)ide analogues were all effective in HBeAg seroconversion, HBeAg loss, and achieving undetectable HBV DNA. Telbivudine was associated with higher HBeAg seroconversion compared with entecavir. For HBeAg loss rate and proportion of achieving undetectable HBV DNA, tenofovir ranked as the best. Entecavir might be the most potent in the normalization of alanine aminotransferase (ALT). The nucleos(t)ide analogues did not have higher serious adverse events rate as compared with placebo.

Conclusion

The nucleos(t)ide analogues are all effective for HBeAg seroconversion, HBeAg loss, undetectable HBV DNA, and most are effective for ALT normalization in adults with CHB. RCTs of multi-center, low risk of bias, and long-term follow-up are still needed.

中文翻译：

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Nucleos（t）ide类似物用于治疗慢性乙型肝炎：网络荟萃分析的系统评价。

目标

慢性乙型肝炎（CHB）是由乙型肝炎病毒（HBV）感染引起的主要全球性健康问题，可能使患者处于因肝硬化和肝癌而死亡的高风险中。但是，CHB可以用核苷酸类似物治疗。我们的目标是评估核苷酸（t）ide类似物治疗CHB患者的有效性和安全性。

方法

进行了系统的文献检索。进行了直接比较荟萃分析和网络荟萃分析（NMA）。

结果

三十六项随机对照试验（RCT）符合纳入标准。与安慰剂相比，核苷酸（t）ide类似物对HBeAg血清转化，HBeAg丢失和无法检测到的HBV DNA均有效。与恩替卡韦相比，替比夫定与更高的HBeAg血清转化率有关。对于HBeAg丢失率和无法检测到的HBV DNA的比例，替诺福韦名列最佳。恩替卡韦可能是最有效的丙氨酸转氨酶（ALT）标准化方法。与安慰剂相比，核苷酸（t）ide类似物没有更高的严重不良事件发生率。

结论

核苷酸（t）ide类似物均对HBeAg血清转化，HBeAg丢失，无法检测到的HBV DNA有效，并且对CHB成人的ALT正常化最有效。仍然需要多中心RCT，低偏倚风险和长期随访。