Hepatitis B vaccine

Overall the evidence strongly favours vaccination (OR=0.33; 95% CI (0.21, 0.53)).

Our estimates of effectiveness and safety in the high risk group favour treatment, the OR for cases of HB being 0.34; 95% CI (0.21, 0.55).

The analysis also revealed a non-significant trend towards benefit in the lower risk health-care workers (Dienstag trial, OR 0.26 (0.05, 1.30).

HepB vaccine is 80% to 100% effective in preventing infection or clinical hepatitis in those who receive the complete vaccine series.

The reduction of incidence in the vaccinees was as high as 92.3%; none of the vaccinees with a detectable immune response to the vaccine had clinical hepatitis B or asymptomatic antigenemia.

For the first 18 months of follow-up, hepatitis B or subclinical infection developed in only 1.4 to 3.4% of the vaccine recipients as compared with 18 to 27% of placebo recipients (P < 0.0001).

Studies on the secular trend of liver disease risk also documented a 68% decline in mortality from fulminant hepatitis in infants and a 75% decrease in the incidence of hepatocellular carcinoma in children 6-9 years of age after the national vaccination program began.

The incidence of acute symptomatic HBV infection in persons <20 years of age fell from cases 19/100,000 in 1981-1982 to 0/100,000 in 1993-1994.

Compared with placebo/no intervention, vaccine reduced hepatitis B occurrence (RR 0.28, 95% confidence interval (CI) 0.20 to 0.40, 4 trials).

Compared with placebo/no intervention, hepatitis B immunoglobulin or the combination of vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (hepatitis B immunoglobulin: RR 0.50, 95% CI 0.41 to 0.60, 1 trial; PDV plus hepatitis B immunoglobulin: RR 0.08, 95% CI 0.03 to 0.17, 3 trials).

Compared with placebo/no intervention, hepatitis B immunoglobulin or the combination of vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (hepatitis B immunoglobulin: RR 0.50, 95% CI 0.41 to 0.60, 1 trial; PDV plus hepatitis B immunoglobulin: RR 0.08, 95% CI 0.03 to 0.17, 3 trials).

Compared with vaccine, vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (RR 0.54, 95% CI 0.41 to 0.73, 10 trials).

No significant differences of hepatitis B occurrence were found comparing recombinant vaccine (RV) versus plasma-derived vaccine (PDV) (RR 1.00, 95% CI 0.71 to 1.42, 4 trials) and high-dose versus low-dose vaccine (PDV: RR 0.97, 95% CI 0.55 to 1.68, 3 trials; RV: RR 0.78, 95% CI 0.31 to 1.94, 1 trial).

No significant differences of hepatitis B occurrence were found comparing recombinant vaccine (RV) versus plasma-derived vaccine (PDV) (RR 1.00, 95% CI 0.71 to 1.42, 4 trials) and high-dose versus low-dose vaccine (PDV: RR 0.97, 95% CI 0.55 to 1.68, 3 trials; RV: RR 0.78, 95% CI 0.31 to 1.94, 1 trial).

No significant differences of hepatitis B occurrence were found comparing recombinant vaccine (RV) versus plasma-derived vaccine (PDV) (RR 1.00, 95% CI 0.71 to 1.42, 4 trials) and high-dose versus low-dose vaccine (PDV: RR 0.97, 95% CI 0.55 to 1.68, 3 trials; RV: RR 0.78, 95% CI 0.31 to 1.94, 1 trial).

HBIG reduced mother-to-child transmission (MTCT) of HBsAg when compared with no intervention (179/2769 (6%) with HBIG versus 537/2541 (21%) with no intervention; RR 0.30, TSA-adjusted CI 0.20 to 0.52; I2 = 36%; 29 trials; 5310 participants; very low quality evidence).

Results indicate that the overall cumulative incidence of HBV breakthrough infection 5-20 years post-primary vaccination was 0.007 [95% CI: 0.005 to 0.010] with a variation among studies from 0 to 0.094.

Several important controlled randomized clinical trials on hepatitis B immunoglobulin and vaccine in Taiwan demonstrated an 80-90% protective effect among infants of mothers who were positive for either hepatitis B envelope antigen or hepatitis B surface antigen.

Comparing cohorts with universal vaccination to those without vaccination, relative prevalences were 0.24 (95% confidence interval, CI: 0.16-0.35) for HBsAg and 0.23 (95% CI: 0.17-0.32) for HBcAb.

Comparing cohorts with universal vaccination to those without vaccination, relative prevalences were 0.24 (95% confidence interval, CI: 0.16-0.35) for HBsAg and 0.23 (95% CI: 0.17-0.32) for HBcAb.

For populations with targeted vaccination, relative prevalences were 0.32 (95% CI: 0.24-0.43) and 0.33 (95% CI: 0.23-0.45), respectively.

The pooled risks of infection were 6·16% (95% CI 3·05-12·04; 155/1407) in the no vaccination group, 0·21% (0·04-1·15; 10/3425) in children who received their first dose at 6-8 weeks, and 0·05% (0·00-1·32; 3/2902) in children who received their first dose at birth.

The pooled risks of infection were 6·16% (95% CI 3·05-12·04; 155/1407) in the no vaccination group, 0·21% (0·04-1·15; 10/3425) in children who received their first dose at 6-8 weeks, and 0·05% (0·00-1·32; 3/2902) in children who received their first dose at birth.

Among PLWH who received the HBV vaccine, the pooled response rate of HBV vaccination was 71.5% (95% CI 64.0%-77.9%, p < 0.001).

Compared with the standard dose (65.5%, 95% CI 53.1%-76.1%), the double dose (75.2%, 95% CI 66.2%-82.5%) was associated with a better response rate [Q(1) = 19.617, p < 0.001].

When stratified by schedule, the four-dose schedule (89.7%, 95% CI 83.1%-93.9%) had a higher response rate than the three-dose schedule (63.3%, 95% CI 56.6%-69.4%) and the difference was significant [Q(1) = 88.305, p < 0.001].

Meta-analysis of data from 718 adults (14 trials) on long-term dialysis demonstrated that intramuscular hepatitis B vaccination was less likely to achieve seroprotection than intradermal vaccination, the pooled odds ratio was 0.454 (95% CI, 0.3; 0.67), P = 0.001.

This difference did not persist during follow-up (6-60 months after completing vaccine schedule), the pooled odds ratio being 0.718 (95% CI, 0.36; 1.47), NS.

Pooling of study results demonstrated a significantly decreased risk of response to hepatitis B vaccine among older dialysis patients (overall risk ratio: 0.74; 95% confidence intervals: 0.70-0.79).

Aggregation of study results showed a significant decrease in response rates among the diabetic vs. the nondiabetic patients [pooled odds ratio=0.52 (95% CI 0.38-0.71)].

The incidence of seroconversion was not increased with double-dose vaccination overall [risk ratio (RR) 1.17, 95% confidence interval (CI) 0.98-1.39], by dialysis requirement or vaccine type.

The incidence of seroprotection (reported by only four studies) was increased with double-dose vaccination overall (RR 1.53, 95% CI 1.17-2.00) but not by dialysis requirement.

The combined seroconversion rates were 91%, 83%, 86%, 81%, 76%, and 32% at 1, 2, 3, 6-9, 12, and 20 months in the ID group, respectively, and 55%, 72%, 58%, 44%, 24%, and 0% in the IM group, respectively.

Based on a random-effects model, the pooled rate of a response to HBV vaccination among patients with IBD was 61% (95% confidence interval [CI]: 53-69).

In addition, no immunosuppressive therapy was predictive of an immune response compared to immunomodulatory (RR: 1.33; 95% CI: 1.08-1.63) or anti-tumor necrosis factor-α (anti-TNF-α) (RR: 1.57; 95% CI: 1.19-2.08) therapy.

HepB vaccination and 1 dose of HBIG administered within 24 hours after birth are 85% to 95% effective in preventing chronic HBV infection.

HepB vaccine administered alone beginning within 24 hours after birth is 70% to 95% effective in preventing perinatal HBV infection.

With postexposure prophylaxis, comprised of HepB vaccine and hepatitis B immune globulin (HBIG) at birth, followed by completion of the HepB vaccine series, 0.7% through 1.1% of infants develop infection; infants born to mothers with high viral loads are at greatest risk for infection despite receipt of HepB vaccine and HBIG.

Immunogenicity and Vaccine Efficacy Hepatitis B Vaccine Efficacy Over 90% of infants, children, adolescents, and healthy adults <40 years develop protective antibody response following complete series 80 to 100% effective in preventing infection or clinical hepatitis following complete series Larger doses or increased number of doses necessary for dialysis patients and immunocompromised persons Booster doses not recommended for immunocompetent persons More than 90% of infants, children, and adolescents and more than 90% of healthy adults younger than age 40 years develop a protective antibody response following a complete HepB vaccine series.

In adults receiving Heplisav-B, 90 to 100% develop adequate antibody after the 2-dose series.

Additional vaccine doses for persons who receive postvaccination testing and who fail to respond to a primary vaccination series administered in the deltoid muscle produce adequate response in 15% to 25% of these persons after 1 additional dose and in 30% to 50% after 3 additional doses.

Fewer than 5% of persons receiving 6 doses of HepB vaccine administered by the appropriate schedule in the deltoid muscle fail to develop detectable anti-HBs antibody.

In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance.

RESULTS: At the primary endpoint, the SPR for the HBsAg-1018 group (90.0%) was superior to the SPR for the HBsAg-Eng group (70.5%) with an SPR difference of 19.5% (95% CI, 14.7%, 24.7%).

At week 28 when the SPR peaked in the HBsAg-Eng group (72.8%), the SPR in the HBsAg-1018 group (94.8%) was significantly higher than in the HBsAg-Eng group.

One month after the final vaccine dose, the seroprotection (anti-HBs >or=10mIU/ml) rate in the two-dose (20 microg) group (233/241 individuals -96.7% seroprotected) was non-inferior to the seroprotection rate in the three-dose (10 microg) group (111/113 individuals -98.2% seroprotected).

RESULTS: Among 243 persons (56%) who responded to the original primary series but received no subsequent doses during the 30-year period, 125 (51%) had an anti-HBs level ≥10 mIU/mL.

Among participants with anti-HBs levels <10 mIU/mL who were available for follow-up, 75 of 85 (88%) responded to a booster dose with an anti-HBs level ≥10 mIU/mL at 30 days.

CONCLUSIONS: Based on anti-HBs level ≥10 mIU/mL at 30 years and an 88% booster dose response, we estimate that ≥90% of participants had evidence of protection 30 years later.

Among the 112 persons in group 1 who responded to the original primary series, 53 (47.3%) had an anti-HBs level ≥10 mIU/ml.

CONCLUSIONS: Based on anti-HBs level ≥10 mIU/ml at 35 years and a 73.7% booster dose response, we estimate that 86% of participants had evidence of protection 35 years later.

The overall proportion with serologic evidence of protection was 95% at 22 years, 95% at 30 years, 88% at 35 years, and 91% at 41 years after vaccination.

The overall proportion with serologic evidence of protection was 95% at 22 years, 95% at 30 years, 88% at 35 years, and 91% at 41 years after vaccination.

At 41 years, 32% had circulating anti-HBs ≥10 mIU/mL, and 59% had immune memory.

During 41 years of follow-up, 16 (1%) persons had evidence of a breakthrough infection; none developed chronic hepatitis B.

RESULTS: Vaccine efficacy 15 years after vaccination was 67.0% against infection as manifest by anti-HBc positivity (95% CI 58.2-74.6%), and 96.6% against HBsAg carriage (95% CI 91.5-100%).

RESULTS: Vaccine efficacy 15 years after vaccination was 67.0% against infection as manifest by anti-HBc positivity (95% CI 58.2-74.6%), and 96.6% against HBsAg carriage (95% CI 91.5-100%).

RESULTS: Comparing fully vaccinated vs unvaccinated GHIS participants, current HBV infection was 0.8% (2/255) vs 12.4% (59/475), p < 0.0001, suggesting 94% (95% CI 77-99%) vaccine efficacy.

Comparing fully vaccinated vs unvaccinated participants, anti-HBc was 27.4% (70/255) vs 56.0% (267/475), p < 0.00001.

In children born after the end of GHIS, HBsAg prevalence has remained low; 1.4% (15/1103) in those born between 1990-97, and 0.3% (9/35150) in those born between 1998-2007.

A positive maternal HBsAg status was found in 86% of vaccine failures.

RESULTS: The seropositive rates for HBsAg, anti-HBs, and anti-HBc were 1.2%, 50.5%, and 3.7%, respectively, in those born after the vaccination program (<20 years of age) in 2004.

very different between subjects born after the program in 2009 and the baseline group in 1984 (0.9% vs. 10%, 55.

A series of prevalence surveys on children born before and after the national vaccination program began disclosed a steady decrease in seroprevalence of hepatitis B surface antigen in Taiwan, with 78-87% effectiveness after the national vaccination program was launched.

Studies on the secular trend of liver disease risk also documented a 68% decline in mortality from fulminant hepatitis in infants and a 75% decrease in the incidence of hepatocellular carcinoma in children 6-9 years of age after the national vaccination program began.

RESULTS: The average annual incidence of hepatocellular carcinoma in children 6 to 14 years of age declined from 0.70 per 100,000 children between 1981 and 1986 to 0.57 between 1986 and 1990, and to 0.36 between 1990 and 1994 (P<0.01).

The incidence of hepatocellular carcinoma in children 6 to 9 years of age declined from 0.52 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (P<0.001).

From 2004 to 2018, CLD mortality decreased by 26% (adjusted rate ratio [aRR], 0.74; 95% CI, 0.70-0.82), HCC mortality decreased by 50% (aRR, 0.50; 95% CI, 0.45-0.58), and HCC incidence decreased by 53% (aRR, 0.47; 95% CI, 0.44-0.52).

A sharply declining association by cohort was observed from the 1982 to 1986 birth cohort to the 2007 to 2011 birth cohort, during which CLD mortality decreased by 82% (aRR, 0.18; 95% CI, 0.00-1.13), HCC mortality decreased by 63% (aRR, 0.37; 95% CI, 0.09-0.68), and HCC incidence decreased by 80% (aRR, 0.20; 95% CI, 0.00-0.48).