Nucleos(t)ide analogues for the treatment of chronic hepatitis B: a systematic review with network meta-analysis

ABSTRACT

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.

KEYWORDS:

• Chronic hepatitis B
• nucleos(t)ide analogues
• systematic review
• network meta-analysis
• treatment

Article highlights

• Chronic hepatitis B (CHB) may last a lifetime, possibly leading to serious illnesses such as cirrhosis, liver failure, or liver cancer. Nucleos(t)ide analogues have been widely used for patients with CHB.

• The scientific methodological framework of NMA can provide evidence-based support to evaluate comparative effectiveness and safety data of nucleos(t)ide analogues.

• Compared with placebo, the nucleos(t)ide analogues were all effective in viral response (HBeAg seroconversion, HBeAg loss, undetectable HBV DNA), and most were effective for biochemical response (ALT normalization).

• The nucleos(t)ide analogues did not have higher serious adverse events rate as compared with placebo.

• Telbivudine was associated with higher HBeAg seroconversion compared with entecavir and lamivudine. For HBeAg loss rate and undetectable HBV DNA, tenofovir ranked as the best. Entecavir might be the most potent nucleos(t)ide in the normalization of ALT for CHB patients. Future RCTs need to be improved in line with the reporting standards. RCTs of multi-center, low risk of bias, and long-term follow-up are still needed to examine other outcomes, such as incidence of hepatocellular carcinoma, survival rate, and quality of life.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was funded by the National Natural Science Foundation of China (Project No. 71603138); Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents; Bristol-Myers Squibb Shanghai Pharmaceutical Co., Ltd.