NEWS & VIEWS HEPATITIS

HBV vaccine—the first vaccine to prevent cancer Stanislas Pol Refers to Qu, C. et al. Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong Hepatitis B intervention study: a cluster randomized controlled trial. PLoS Med. http://dx.doi.org/10.1371/ journal.pmed.1001774.

HBV is a common infection that accounts for hundreds of thousands of deaths each year, despite the availability of a vaccine. A new study has evaluated the Chinese neonatal vaccination programme and found that the vaccine considerably reduces the incidence of liver diseases, and that a booster vaccine might be effective. HBV infection is a common viral infection. A safe and effective vaccine has been available for >30 years; however, worldwide, >350 million people are chronically infected with HBV1 and it accounts for ~780,000 deaths each year.2 HBV-related mortality is mainly associated with cirrhosis and its complications, including hepatocellular carcinoma (HCC).1 A high prevalence of HBV infection has persisted in areas where the virus is endemic (such as Asia and Africa, where >8% of the population is chronically infected1), which could be attributable to insufficient public health policies, including the limited implementation of an efficient preventive strategy. HBV is highly contagious and is transmitted by close person-to-person contact, especially in early childhood, sexual and parenteral exposure.1,3 Most infections occur perinatally (mainly vertical mother-to-child transmission): around half of chronic infections in the Asia–Pacific region and one-fifth in Africa, South America and the Middle East occur in this way.1 Vertical transmission of HBV usually occurs during delivery and whether the virus is transmitted depends on the mother’s viral load.3 The WHO recommends that routine infant immunization programmes are implemented in all countries. Furthermore, in countries where HBV is endemic, they recommend that the first dose of the HBV vaccine is given as soon as possible and in practice before the baby is 24 h old, which corresponds to a birth-dose vaccine without testing the hepatitis B surface antigen (HBsAg) status of the mother.4

In the 1980s, a programme of systematic vaccination or serovaccination of children born to women with HBV infection that was subsequently rolled out to all children and adolescents and was followed by universal vaccination was performed in Singapore, Taiwan and Alaska. These programmes resulted in a major reduction in the number of HBsAg carriers, in acute and chronic HBV infections and in liver-related mortality, including a reduced rate of HCC in both adults and children within the decade following vaccination.5–7 These findings suggest that the HBV vaccine was the first vaccine to dramatically reduce the risk of a cancer, that is, HCC (as well as other acute or chronic HBV-related liver diseases). Previous studies have not been able to attribute the reduced risk of HCC to HBV vaccination as a result of the potential differences in baseline characteristics and in exposures to other risk factors between the immunized and nonimmunized historical comparison groups. Therefore, the Qidong Hepatitis B Intervention Study (QHBIS)8 aimed to examine the preventive efficacy of HBV vaccination against HCC  and other liver diseases in young adulthood and to establish a causal link between HBV v­accination and the observed benefits. The QHBIS is a population-based, cluster, randomized, controlled trial of HBV vaccination that was conducted between 1983 and 1990 in China and involved 80,000 neonates

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY © 2015 Macmillan Publishers Limited. All rights reserved

who were randomly assigned to the vaccination or control groups.8 38,366 (97.64%) participants completed the three-dose course (each of 5 μg) of the plasma-derived HBV vaccination and 34,441 neonates in the control towns received neither vaccine nor placebo; the median follow-up was 25 years. The three main messages from this study are that, firstly, neonatal vaccination is associated with a reduction in the number of people carrying HBsAg. Secondly, this reduction is followed by a dramatic decline in the occurrence of liver diseases, including HCC, acute-on-chronic liver failure or fulminant hepatitis. Thirdly, a catchup vaccination in control individuals or a booster vaccination in vaccinated children reduces HBsAg prevalence and improves i­mmunogenicity, respectively. In comparison with the control group, the vaccination group had a significantly lower incidence of HBsAg seropositivity, with 2.16% at age 10–11 years and 1.83% at 19–28 years in vaccinated children versus 9.03% and 6.73% (P = 0.0001) in the control group, respectively. This finding suggests that the vaccine has a protection efficacy against HBsAg seropositivity of 78% (95% CI 75–80%) and 72% (95% CI 68–75%) in these age groups, respectively. The incidence of HCC was also reduced (HR = 0.16, 95% CI 0.03–0.77), with an 84% protective efficacy against developing HCC before age 30 years (as a negative control, the incidence of brain tumour was similar in the vaccination group [0.52 per 100,000] and the control group [0.71 per 100,000]). Furthermore, mortality as a result of severe end-stage chronic liver diseases, including HCC, acute-on-chronic liver failure and chronic liver failure, was also reduced (HR = 0.30, 95% CI 0.11–0.85). The efficacy of neonatal

NPG

ADVANCE ONLINE PUBLICATION  |  1

NEWS & VIEWS

‘‘

Previous studies have not been able to attribute the reduced risk of HCC to HBV vaccination…

’’

vaccination against severe end-stage chronic liver diseases was 70% (95% CI 15%–89%). Mortality as a result of fulminant hepatitis was also reduced by neonatal vaccination (HR = 0.31, 95% CI 0.15–0.66) with an e­fficacy of 69% (95% CI 34%–85%). Finally, without randomization, a catch-up or booster vaccination was administrated to 23,368 (67.8%) control individuals at age 10–14 years and to 28,988 (73.8%) children in the vaccination group at the same age. The rate of HBsAg seropositivity was lower in those who received the catch-up vaccination than in those who did not receive it (6.26% versus 7.76%, respectively, P = 0.0002). Even if the protection efficacy of 21% (95% CI 10–30%) was substantially weaker than that achieved with neonatal vaccination, a significant difference in HBsAg seroprevalence was observed in the control group following catch-up vaccination (P = 0.0008). The QHBIS study has some limitations that could affect the accuracy of the conclusions: the small number of events (14 instances of HCC, nine instances of acute-on-chronic liver failure and 40 instances of fulminant hepatitis) despite the long follow-up; and the absence of randomization of the catch-up or booster vaccination. Despite these limitations, the study clearly shows that neonatal vaccination in regions that are endemic for HBV dramatically reduces the level of HBsAg carriage, which results in a considerable reduction in HBV-related mortality. In developed

countries where hepatitis B immune globulin is available, testing the maternal HBsAg status is recommended. The recommendations also suggest the administration of a sero­ vaccination to the neonates of HBsAg-positive mothers in the first 12 h of life (an intra­ muscular injection of HBV vaccine together with an intramuscular injection of 30 IU/kg of hepatitis B immune globulin at another intramuscular site, followed by booster vaccine injections at 1 month and 6 months).9,10 An important practical message from this study, which needs confirmation by a randomized trial, is that a catch-up vaccination received at age 10–14 years reduced HBsAg seroprevalence in young adults with roughly 20% efficacy (compared with 72% efficacy for neonatal vaccination). In addition, a booster injection at age 10–14 years might improve the immunological memory to HBV and could thus help to prevent h­orizontal HBV infection in young adults. In conclusion, the QHBIS study provides additive evidence that neonatal HBV vaccination can notably reduce the risk of HCC and other chronic liver diseases in young adult­h ood. Further­m ore, the findings suggest that an adolescent booster should be con­sidered for individuals born to HBsAgpositive mothers who were HBsAg-negative to consolidate vaccination efficacy. Université Paris Descartes, INSERM UMS20, Institute Pasteur, APHP, Unité d’Hépatologie, Hôpital Cochin, 27 Rue du Faubourg Saint Jacques, 75679 Paris Cedex 14, France. [email protected] Acknowledgements S.P. would like to acknowledge the help of W. Gerlich in preparing this manuscript.

2  |  ADVANCE ONLINE PUBLICATION

Competing interests The author declares no competing interests. 1.

Lavanchy, D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J. Viral Hepat. 11, 97–107 (2004). 2. World Health Organization. Hepatitis B [online], http://www.who.int/mediacentre/factsheets/ fs204/en/ (2014). 3. McMahon, B. J. et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carriers state. J. Infect. Dis. 151, 599–603 (1985). 4. [No authors listed] Hepatitis B vaccines [French]. Wkly Epidemiol. Rec. 28, 255–263 (2004). 5. Huang, K. & Lin, S. Nationwide vaccination: a success story in Taiwan. Vaccine 18 (Suppl. 1), S35–S38 (2000). 6. Chang, M. H. et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N. Engl. J. Med. 336, 1855–1859 (1997). 7. McMahon, B. J. et al. Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program. Hepatology 54, 801–807 (2011). 8. Qu, C. et al. Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong Hepatitis B intervention study: a cluster randomized controlled trial. PLoS Med. http:// dx.doi.org/10.1371/journal.pmed.1001774. 9. Chakvetadze, C. et al. Efficacy of hepatitis B sero-vaccination in newborns of African HBsAg positive mothers. Vaccine 29, 2846–2849 (2011). 10. Soleimani Amiri, M. J., Hasanjani Roushan, M. R., Baiany, M., Taheri, H. & Hasanjani Roushan, M. Outcomes of passive-active immunoprophylaxis given to infants of mothers infected with hepatitis B virus in Babol, Iran. J. Clin. Virol. 49, 283–285 (2010). Published online 17 February 2015; doi:10.1038/nrgastro.2015.28

www.nature.com/nrgastro © 2015 Macmillan Publishers Limited. All rights reserved

Hepatitis: HBV vaccine--the first vaccine to prevent cancer.

Hepatitis: HBV vaccine--the first vaccine to prevent cancer. - PDF Download Free
163KB Sizes 0 Downloads 8 Views