HBV Catch-up Vaccination in Children and Adults with Incomplete or Unknown Vaccination to Reduce Hepatitis B-related Morbidity: A Systematic Review.

Background: Hepatitis B virus causes life-threatening chronic liver infection and increases the risk of death from cirrhosis and liver cancer. A three-dose series of universal HBV vaccination initiated from birth is effective against the disease. It is unclear if catch-up vaccination is also effective in those with incomplete or no HBV vaccination. Objective: To review the evidence on the effect of HBV catch-up vaccination on children and adults to decrease HBV-related morbidity. Methods: We searched MEDLINE, Cochrane CENTRAL, ChinaXiv, MedRXIV, BioRXIV, Google Scholar, and ongoing and completed trials on USA: https://clinicaltrials.gov/; China: http://www.chictr.org.cn/searchprojen.aspx, and WHO: https://www.who.int/clinical-trials-registry-platform. The last search date was 30 June 2023. We considered experimental or observational studies, meta-analysis/systematic reviews, completed trials and preprints that investigated the efficacy of catch-up HBV immunization in decreasing morbidity from hepatitis B infection including acute and chronic hepatitis B infection, liver cirrhosis, and hepatocellular carcinoma. There was no age and language restriction. Two reviewers independently rated the quality of included studies using Newcastle - Ottawa Quality Assessment Scale for cohort and cross-sectional studies. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was used to determine the certainty of evidence. Data was presented as number (%) for categorical values. Differences between the unvaccinated and vaccinated group was described as relative risk or odds ratio for categorical variables. Data was pooled using Review Manager 5.4. Results: A total of four observational studies were included, one of which had data in children and adults [two (one with data in adults) studies in children; 3 in adults]. The cross-sectional study was assessed as good quality; and the three cohorts as fair to good. In children, a high certainty evidence study showed that catch up vaccination in 9 to 18 years old decreased risk of HBsAg positivity [RR: 0.09 (0.004, 0.21)], reduced HBV DNA detection [RR: 0.084 (0.026, 0.273)], and increased anti-HBs seroconversion [RR: 2.08 (1.84, 2.33)]. The quality of evidence was deemed high based on a large treatment effect. Another low certainty evidence study in Italy showed that HBV mass immunization in 0-10 years old decreased the prevalence of HBsAg anti-HBc and increased anti-HBs seroconversion after vaccination. In adults, three low certainty evidence studies were included. Two studies showed decreased incidence of acute hepatitis B [OR: 0.08 (0.05, 0.12), I2 = 33%]. Another study demonstrated a decreased prevalence of hepatocellular carcinoma with HBV vaccination with the incidence ratio of vaccinated with chronically infected at 0.04 (0.02, 0.07) showing a large magnitude of benefit for vaccination against HCC when chronic HBV infection is prevented. The studies were deemed to have low quality due to issue of directness and study design. Conclusion: HBV catch-up vaccination in adults is effective in decreasing the prevalence of acute hepatitis B and hepatocellular carcinoma. It likewise decreased the prevalence of HBsAg and anti-HBc, and provided anti-HBs protection in 0 to 18 years.