Molecular and Genomic Epidemiology Center, China Medical University Hospital, Taichung, Taiwan.
Hepatitis B immunization has been documented to prevent fulminant hepatic failure and hepatocellular carcinoma by historical comparison studies in Taiwan. This study aimed to assess long-term risks and predictors of various liver diseases associated with incomplete immunization in 3.8 million vaccinees. Profiles of National Hepatitis B Immunization Registry, National Cancer Registry and National Death Certification Registry were linked to ascertain newly-diagnosed cases of hepatocellular carcinoma and deaths from fulminant hepatic failure and chronic liver diseases from infancy to early adulthood of 3,836,988 newborn vaccinees. Cox's proportional hazards models were used to estimate hazard ratios for various risk predictors. There were 49 newly-developed cases of hepatocellular carcinoma, 73 deaths from fulminant hepatic failures and 74 deaths from chronic liver diseases during the follow-up of 41,854,715 person-years. There were striking differences between unvaccinated and vaccinated newborns after the launch of national immunization program for the hepatocellular carcinoma incidence (0.293 vs. 0.117 per 100,000 person-years), fulminant hepatic failure mortality (0.733 vs. 0.174 per 100,000 person-years), and chronic liver diseases mortality (2.206 vs. 0.177 per 100,000 person-years). Among vaccinees, incomplete immunization was the most important risk predictor of hepatocellular carcinoma, fulminant hepatic and chronic liver diseases showing a hazard ratio (95 percent confidence interval, P-value) of 2.52 (1.25-5.05, P=0.0094), 4.97 (3.05-8.11, P<0.0001), and 6.27 (3.62-10.84, P<0.0001), respectively, after adjustment for maternal hepatitis B serostatus. Conclusion: Hepatitis B immunization can significantly prevent the long-term risk of hepatocellular carcinoma, fulminant hepatic failure and chronic liver diseases from infancy to early adulthood. Incomplete immunization with hepatitis B immunoglobulin or vaccines was the most important risk predictor of the liver disease among vaccinees.