Hepatitis B immunisation in persons not previously exposed to hepatitis B or with unknown exposure status
Editorial Group: Cochrane Hepato-Biliary Group
Published Online: 16 JUL 2008
Assessed as up-to-date: 4 MAY 2008
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Mathew JL, El Dib R, Mathew PJ, Boxall EH, Brok J. Hepatitis B immunisation in persons not previously exposed to hepatitis B or with unknown exposure status. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD006481. DOI: 10.1002/14651858.CD006481.pub2.
- Publication Status: Edited (no change to conclusions)
- Published Online: 16 JUL 2008
The benefits and harms of hepatitis B vaccination in persons not previously exposed to hepatitis B infection or with unknown exposure status have not been established.
To assess the benefits and harms of hepatitis B vaccination in people not previously exposed to hepatitis B infection or with unknown exposure status.
Trials were identified from The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded (last search, March 2007). Additionally, we contacted experts and vaccine manufacturers, and read through reference lists for eligible trials.
Randomised clinical trials comparing hepatitis B vaccine versus placebo, no intervention, or another vaccine in persons not previously exposed to hepatitis B (HBsAg negative) or with unknown exposure status.
Data collection and analysis
The primary outcome was hepatitis B infection (detecting HBsAg, HBeAg, HBV DNA, or anti-HBc). Secondary outcomes were lack of sero-protection, antibody titre, clinical complications, adverse events, lack of compliance, and cost-effectiveness. Dichotomous outcomes were reported as relative risk (RR) with 95% confidence interval (CI), using intention-to-treat analysis assuming an unfavourable event for missing data. Sensitivity analyses based on methodological quality (risk of bias), available data analysis, intention-to-treat analysis assuming a favourable event for missing data, best-case scenario, and worst-case scenario were conducted.
Twelve trials were eligible. All had high risk of bias and reporting was inconsistent. Hepatitis B vaccine did not show a clear effect on the risk of developing HBsAg (RR 0.96, 95% CI 0.89 to 1.03, 4 trials, 1230 participants) and anti-HBc (RR 0.81, 95% CI 0.61 to 1.07; 4 trials, 1230 participants, random-effects) when data were analysed using intention-to-treat analysis assuming an unfavourable event for missing data. Analysis based on data of available participants showed reduced risk of developing HBsAg (RR 0.12, 95% CI 0.03 to 0.44, 4 trials, 576 participants) and anti-HBc (RR 0.36, 95% CI 0.17 to 0.76, 4 trials, 576 participants, random-effects). Intention-to-treat analysis assuming favourable outcome for missing data showed similar reduction in risk. Hepatitis B vaccination had an unclear effect on the risk of lacking protective antibody levels (RR 0.57, 95% CI 0.26 to 1.27, 3 trials, 1210 participants, random-effects). Development of adverse events was sparsely reported.
In people not previously exposed to hepatitis B, vaccination has unclear effect on the risk of developing infection, as compared to no vaccination. The risk of lacking protective antibody levels as well as serious and non-serious adverse events appear comparable among recipients and non-recipients of hepatitis B vaccine.
Plain language summary
In children or grown-ups who have not been previously exposed to hepatitis B infection or whose exposure status is not known, hepatitis B vaccination as compared with no hepatitis B vaccination has an unclear effect on the risk of developing hepatitis B infection
Several million people world-wide are infected with hepatitis B virus. The infection may cause serious short-term and long-term effects including portal hypertension, liver failure, liver cancer, and death. Hepatitis B vaccination is reported to be beneficial in some specific groups of people such as babies born to women infected with hepatitis B, health-care workers, and people with long-standing kidney failure. Whether hepatitis B vaccine is beneficial in people who have not been exposed to hepatitis B infection or those whose exposure status is not known is assessed in the present review.
Twelve randomised clinical trials fulfilled the inclusion criteria of this review. Primary analysis of the data based on criteria described beforehand (intention-to-treat model assigning unfavourable outcome for missing data) showed that hepatitis B vaccination has an unclear effect on the risk of developing hepatitis B infection. Analysis of data of available participants in the various trials showed that as compared to not vaccinating, hepatitis B vaccination reduces the risk of developing hepatitis B infection; by 88% for hepatitis B surface antigen marker and 62% for anti-core antibody marker. One should note, that these findings are based on only four randomised clinical trials of poor methodological quality involving 1230 participants. When compared with other vaccines or placebo, hepatitis B vaccination results in comparable risk of developing adverse events. This includes serious adverse events such as admission to hospital and convulsions, as well as less serious events such as fever, local redness, and pain. This shows that the risk of developing these adverse events is not more than with other vaccinations. There was not enough data to draw definite conclusions on the effect of hepatitis B vaccination on compliance and cost-effectiveness.