Daniel M. Keller, PhD

November 12, 2012

BOSTON — In a study from the National Institutes of Health of healthcare workers (HCWs) previously vaccinated against hepatitis B virus (HBV) as adults, antibody titers to HBV surface antigen (anti-HBs) waned over time, according to new research.

Naveen Gara, MD, a former research fellow in the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, and now a gastroenterology fellow at the Washington Hospital Center in Washington, DC, reported in a poster session here at Liver Meeting 2012: American Association for the Study of Liver Diseases (AASLD) 63rd Annual Meeting that negative anti-HBs titers were associated with older age at vaccination.

Universal HBV vaccination has greatly reduced the incidence of HBV and hepatocellular carcinoma worldwide. Studies in endemic areas have shown that many children vaccinated at birth have lost anti-HBs. This study explored the durability of the response to the vaccine in individuals vaccinated as adults from a nonendemic area.

HCWs aged 18 to 60 years at the time of their first HBV vaccination were recruited to this prospective study. It had been 10 to 14 years since vaccination for group 1 (n = 50), 15 to 19 years for group 2 (n = 50), and 20 or more years for group 3 (n = 59). All participants were tested for hepatitis B surface antigen (HbsAg), core antibody (anti-HBc), and anti-HBs titers. HCWs who were negative for anti-HBs titers (<12 mIU/mL) were offered HBV booster vaccine, and their titers were measured 1 day, 7 days, and 3 weeks after receiving the booster dose.

The mean age at first vaccination was 31 years in group 1, 32 years in group 2, and 34 years in group 3. Most participants were female (74%) and white (69%). The 3 groups' baseline characteristics were similar except that in group 3 there was a higher rate of needlestick injury (47% vs 20% in group 1 and 26% in group 2) and smoking (32% vs 16% and 12%, respectively; P < .05 for both).

Of the 159 HCWs, 23% were anti-HBs negative (16%, 26%, and 25% negative in groups 1, 2, and 3, respectively). None was positive for HbsAg, which would indicate current infection.

The 36 HCWs without detectable anti-HBs were on average older than the 123 HCWs with detectable titers (51 ± 10 years vs 47 ± 10 years, respectively; P = .04) and were vaccinated at a later age (36 ± 9 years vs 32 ± 9 years; P = .02). There were more smokers in the group with detectable anti-HBs (24%) than in the group with negative titers (8%; P = .04).

The mean anti-HBs titers declined according to advancing age at vaccination, with the highest titers in group 1, intermediate titers in group 2, and the lowest titers in group 3 (P = .02).

"One thing we also looked at is the predictors of who will lose their titers over time, and the only thing that remained predictive by multivariate analysis was the age at vaccination" (P < .001), Dr. Gara commented to Medscape Medical News. "So the older you are at your initial vaccination the more likely you are to lose your titers over time."

Booster Dose Increases Anti-HBs Titers

A booster dose of HBV vaccine was 94% effective among the group that was negative for an anti-HBs titer. Of 34 participants with a negative anti-HBs titer who received a booster dose, 32 responded with increases in titers: 1 participant on day 1 after the booster, 18 at 7 days, and 32 at 21 days.

The study authors recommend that HCWs who were vaccinated at an older age should consider having their anti-HBs levels tested and receiving a booster dose if the anti-HBs titer is negative.

Dr. Gara said boosting should be based on testing titers and boosting those who need it "rather than just boosting everybody." He said in previous economic analyses testing and boosting was more cost-effective than universal boosting.

Brenna Simons, PhD, a research scientist with the Liver Disease and Hepatitis Program of the Alaska Native Tribal Health Consortium in Anchorage, Alaska, said she was interested in Dr. Gara's study because "it's always good to compare and see that our cohort looks a lot like other cohorts."

She told Medscape Medical News that the Advisory Committee on Immunization Practices and the US Centers for Disease Control and Prevention are examining efficacy and cost-effectiveness data and having discussions to formulate recommendations especially focusing on healthcare workers and their protection against HBV in medical settings, including looking at the longevity of the vaccine and its protection.

Dr. Simons noted that universal HBV vaccination went into effect in the United States in 1991. "It's actually the first vaccine given at birth," she said. "All 3 doses are given within 6 months of life, and those groups that we've been watching seem to lose their antibody titers much sooner in life, before the age of 20 — so less than 15 years of longevity maintaining this antibody titer versus those that were originally vaccinated as adults and children, a large portion [of whom] seem to maintain their antibody titers for 30 years."

She wondered what that means for the protection of new healthcare workers. "Those that were infants in 1991 are now entering the healthcare field," she pointed out.

The study was not commercially funded. Dr. Gara and Dr. Simons have disclosed no relevant financial relationships.

The Liver Meeting 2012: American Association for the Study of Liver Diseases (AASLD) 63rd Annual Meeting. Abstract 905. Presented November 11, 2012.

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