A systematic review and meta-analysis assessing the safety and efficacy of the hepatitis E virus vaccine

Hepatitis E virus (HEV) is a global cause of viral hepatitis. While genotypes 1 and 2 cause acute hepatitis in Asia and Africa, genotypes 3 and 4 lead to sporadic acute or chronic hepatitis in America and Europe. Pregnant women, immunosuppressed individuals, and those with chronic liver disease face a higher risk of severe outcomes. HEV recombinant vaccine is approved for outbreak use in China but awaits Food and Drug Administration approval in the USA. This systematic review and meta-analysis aims to assess the safety and efficacy of the HEV vaccine.

We conducted a systematic search in Medline, Cochrane, Scopus, and Embase, employing specific terms for the recombinant HEV vaccine. Eligibility criteria involved all-age individuals receiving recombinant HEV vaccine in randomized controlled trials. Covidence software was used to screen studies, and data extraction encompassed study characteristics, baseline data, and efficacy outcomes by four reviewers. Bias evaluation was completed using Cochrane's RoB 2 tool. Statistical analysis involved use of Revman v5.4 with a random effect model, considering P < 0.05 as statistically significant. Heterogeneity was assessed using the I ² test.

The analysis revealed a statistically significant difference in HEV vaccine efficacy compared to placebo (odds ratio [OR]: 25.16, 95% confidence interval [CI] 9.21, 68.75, P < 0.00001) with a substantial reduction in hepatitis E cases (OR: 0.04, 95% CI 0.01, 0.11, P < 0.00001). In terms of safety, the HEV vaccine exhibited a significant increase in injection pain (OR: 1.56, 95% CI 1.03, 2.36, P = 0.04) and injection bruising (OR: 3.62, 95% CI 1.76, 7.48, P = 0.0005). No statistically significant differences were observed in fever (OR: 1.03, 95% CI 0.86, 1.23, P = 0.76) or headache (OR: 1.15, 95% CI 0.72, 1.84, P = 0.56). Local events significantly increased with the vaccine (OR: 1.50, 95% CI 1.38, 1.63, P < 0.00001). There were no significant differences in systemic events (OR: 1.06, 95% CI 0.86, 1.31, P = 0.59) or serious adverse events (OR: 0.58, 95% CI 0.16, 2.07, P = 0.40).

Our systematic review and meta-analysis demonstrates the significant and favorable impact of the recombinant HEV vaccine on the reduction of HEV cases. However, safety considerations are notable, as the vaccine is associated with a significant increase in injection-related pain and bruising. While localized adverse events were more frequent with the vaccine, there were no statistically significant differences in systemic events, serious adverse events, fever, or headache compared to placebo. These findings emphasize the overall effectiveness of the HEV vaccine in preventing HEV infections but highlight the need for careful monitoring and consideration of potential localized side effects.