Virological Changes of Chronic Hepatitis B Patients with Minimally Elevated Levels of Alanine Aminotransferase: A Meta-Analysis and Systematic Review

BACKGROUND: Chronic hepatitis B (CHB) patients with normal or minimally increased levels of alanine aminotransferase (ALT) are still at the risk of hepatocellular carcinoma, cirrhotic events, and mortality. However, there is a debate over the initiation of antiviral treatment for these patients. This systematic review and mate-analysis aimed to explore this problem. METHODS: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were systematically searched for retrieving relevant studies with risk ratios (RRs) or risk differences (RDs) for virological changes between antivirus-treated and no antivirus-treated CHB patients with ALT levels less than two-fold of the upper limit of normal. Retrieved data ranged from January 1990 to October 2020. RESULTS: Of 6783 abstracts screened, 9 studies met the criteria for inclusion in the systematic review and had a low risk of bias. Among studies that were involved in the meta-analyses, it was found that the rates of HBsAg loss (RR = 12.22, 95% confidence interval (CI): 4.28–34.95, P < 0.001), HBsAg seroconversion (RR = 19.90, 95% CI: 2.75–144.09, P=0.003), and undetectable HBV DNA (RR = 11.89, 95% CI: 2.44–57.89, P=0.002) were both higher in the antiviral treatment group compared with placebo or no treatment group. Subgroup analysis suggested that patients who received interferon (IFN)-based therapy were more inclined to achieve HBsAg loss (P=0.010), HBsAg seroconversion (P=0.020), and HBeAg loss (P=0.002). CONCLUSION: From a sizable population, it was revealed that CHB patients with normal or minimally increased levels of ALT could benefit from the antiviral therapy, especially those who received IFN-based treatment.