Immunizing Infants Against Hepatitis B Tied to Lower Risk of Liver Cancer

By Larry Hand

June 21, 2016

NEW YORK (Reuters Health) - Immunizing infants against hepatitis B virus (HBV) appears to reduce their risk of developing hepatocellular carcinoma as children or young adults, according to a study from Taiwan.

"Clinicians should advise all parents to give three doses of hepatitis B vaccine to their infants, starting from the first day of life, and the third dose should be given at 6 months old. It is very simple and cost-effective to protect against hepatitis B virus infection and liver cancer from childhood to adult life," Dr. Mei-Hwei Chang of the National Taiwan University in Taipei told Reuters Health by email.

"Every pregnant woman should be screened for marker(s) of chronic hepatitis B virus infection, i.e. hepatitis B surface antigen (and hepatitis B e antigen, if possible), to see whether the mother is infectious to her infant during the last trimester of pregnancy or at delivery of the baby. Hepatitis B vaccine and hepatitis B immunoglobulin should be given within 24 hours after birth, as early as possible, for the infants of highly infectious mothers," she said.

Dr. Chang and colleagues analyzed data from two Taiwan HCC registries covering 1,509 patients (6 to 26 years old) diagnosed with HCC from 1983 through 2011. They retrieved data on HBV immunization and prenatal maternal levels of HBV antigens on patients born after 1984 from the Taiwan Center for Disease Control. Using the National Household Registry System, they collected data on birth cohort-specific populations.

Most patients (1,343) were born before and 166 after the Taiwan HBV vaccination program began in 1984. For the first two years, the program covered only infants born to women who were seropositive for HB surface antigen (HBsAg) and HB e antigen (HBeAg), but the program was expanded in 1986 to all infants.

Originally the vaccine consisted of four doses of plasma-derived HBV vaccine given at less than one week of age, one month, two months, and 12 months. In 1992, that changed to three doses of recombinant vaccine given at less than one week, one month, and six months. Neonates of highly infectious mothers carrying HBsAg and HBeAg received HB immunoglobulin within 24 hours after birth.

The researchers calculated HCC incidence rates per 100,000 person-years by dividing the number of patients with HCC by the person-years of the general population. They estimated relative risks for HCC using Poisson regression analysis in vaccinated and unvaccinated cohorts, then stratified patients by age group.

They calculated HCC incidence to be 0.92 per 100,000 person-years in unvaccinated patients and 0.23 in vaccinated persons, they reported in Gastroenterology, online June 6.

Relative to their unvaccinated peers, the risk for HCC among vaccinated individuals was 0.26 for patients aged 6 to 9 years, 0.34 for patients 10 to 14, 0.37 for patients 15 to 19, and 0.42 for patients 20 to 26. These risk reductions were all statistically significant.

Birth cohorts vaccinated later were also at significantly lower risk of HCC than the vaccinated birth cohort of 1984 to 1986.

Among the 166 HCC patients born after the immunization program began in 1984, the two main risk factors for HCC prevention failure were HBV transmission from highly infected mothers and incomplete HBV immunization.

The HCC incident rate was lowest (0.04 per 100,000 person-years) in individuals who had received at least three vaccine doses and whose mothers were HBsAg negative. It was highest among birth cohorts whose mothers were seropositive for HBsAg and HBeAg, up to 3.1 per 100,000 if the neonate did not receive HB immunoglobulin.

"We have provided evidence to prove that hepatitis B vaccine is the first cancer preventive vaccine in humans," Dr. Chang told Reuters Health. "The successful experience of liver cancer prevention by hepatitis B vaccination can serve as an important reference for the development of other cancer preventive vaccines, such as human papillomavirus vaccine to prevent cervical cancer, and others."

She said the next step is to study older populations. "The peak age of liver cancer is in adults of 40 years and older. The first universal hepatitis B vaccination in infancy was started in Taiwan 32 years ago. So we need to study further to understand whether the hepatitis B vaccination in infants could prevent liver cancer in adults of all ages."

Dr. Chang said the results of their study are generalizable to other populations: "Taiwan's experience will be a good reference for other populations."

The authors reported no funding or disclosures.


Gastroenterol 2016.