Elsevier

Vaccine

Volume 34, Issue 40, 14 September 2016, Pages 4835-4841
Vaccine

Hepatitis B vaccine response in obesity: A meta-analysis

https://doi.org/10.1016/j.vaccine.2016.08.027Get rights and content

Highlights

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    We examine the risks of non-response to hepatitis B vaccine in obesity.

  • •

    Decreased vaccine effectiveness was observed in individuals with obesity.

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    The conclusion drawn from the meta-analysis was robust.

Abstract

Background

Hepatitis B vaccination is critical in preventing hepatitis B virus (HBV) infection and transmission. However, the impact of obesity on immune response to hepatitis B vaccine remains unclear.

Methods

We performed a meta-analysis of the literature and summarized the results of immune response to hepatitis B vaccine among persons with and without obesity. We used Pubmed, Embase, Web of Science and Cochrane Library to identify all related studies between January 1973 and November 2015. Unadjusted and adjusted pooled OR and 95% CI were calculated by fixed-effect model or random-effect model according to the heterogeneity of the selected studies.

Results

Totally, 16 studies contributed to the present meta-analysis. Fifteen of them provided absolute numbers of non-responders in obese group and non-obese group. Overall, we found that the obese population was significantly associated with non-response to hepatitis B vaccination (adjusted OR: 2.46, 95% CI: 1.50–4.03). Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with uniform criteria of obesity and restricted to study in adults. No publication bias was observed in the present analysis.

Conclusions

The present meta-analysis suggested that obesity is significantly associated with the decreased response to hepatitis B vaccines. Future studies should be performed to unravel this relationship in order to prevent HBV infection and transmission.

Introduction

Hepatitis B, caused by hepatitis B virus (HBV), is the main attributable risk factor for severe liver diseases including liver fibrosis and hepatocellular carcinoma (HCC). Currently, around one billion people have been infected by HBV and 240 million of them became the chronic carriers of hepatitis B surface antigen (HBsAg). Furthermore, over 780,000 people died each year due to HBV-related diseases [1]. Chronic hepatitis B (CHB) produces severe psychological and economic burdens to the patients and their family. The annual cost per patient with CHB or CHB-related diseases has estimated to exceed $1400 in China [2]. As the most effective means to protect people from HBV infection, the program on immunization with recombinant hepatitis B vaccine was instituted in more than 200 counties since 1982. These efforts resulted in a remarkable decrease of HBsAg positivity worldwide, especially in children and adolescents [3], [4], [5], [6].

Obesity is a major health problem worldwide [7], [8]. As an important risk factor for the chronic diseases such as hypertension, diabetes mellitus and cancers, the economic cost of obesity increased dramatically in recent decades in both developed and developing countries [9]. In addition to these metabolic diseases, it is well known that obesity could produce a chronic inflammatory state including dysregulated cytokine production, reduced natural killer cell activity, altered CD4+/CD8+ T cell balance [10], [11], [12], [13], and decreased response to virus vaccines including hepatitis B vaccines [7]. Previously, Averhoff et al. reported that the hepatitis B vaccination responses were significantly decreased in obese individuals compared to the non-obese people [14], [15]. However, some previous studies suggested that the recombinant hepatitis B vaccine is highly immunogenic and safe in general population including obese subjects [16], [17], [18]. These inconsistent results might be caused by the different vaccine types, immune routes, immune schedules, population size, and the different judgment criteria of obesity and outcome [19], [20], [21]. Since both obesity/overweight and hepatitis B are serious health problems and the obesity/overweight is significantly associated with HBV replication and disease progression, we performed the present meta-analysis to further characterize the available evidences on the relationship between obesity and immune response to hepatitis B vaccine.

Section snippets

Search strategy

The period of the present literatures search was between January 1973 and November 2015. All relevant studies were searched from four electronic search engines (Pubmed, Embase, Web of Science and Cochrane Library), and examined by two investigators independently (Fan and Shen). Discrepancies between two reviewers were resolved through serious discussions until final consensus was achieved. The terms of “obesity”, “body mass index”, “BMI”, “hepatitis B vaccine” and other related words to this

Literature search

Of 714 original papers retrieved, only 16 studies met the inclusion criteria pre-defined [5], [14], [17], [19], [22], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34]. 698 studies were excluded (Fig. 1).

Characteristics of the included studies and the population

As shown in Table 1, a total of 12,084 eligible subjects from 16 studies (3 cross-sectional studies, 7 cohort studies and 6 RCT) were finally included in this analysis. Among 16 studies, five studies were conducted in health care workers (HCW), one study was performed in

Discussion

Because the gene expression of HBV and key metabolic genes in hepatocytes were shown to be similarly regulated in animal models [35], HBV was also considered as a “metabolovirus” and the effects of metabolic diseases on HBV infection have been widely discussed before. By following-up a cohort study of 500 patients carried with HBsAg in Taiwan, Huo et al. suggested that diabetes was an independent factor associated with liver cirrhosis [36]. Additionally, accumulative evidences have indicated

Conclusions

In summary, our results suggested that obesity was significantly associated with the lower response to hepatitis B vaccination. In order to further prevent and control HBV infection and transmission, more studies are needed to design better vaccination strategies in obesity/overweight persons in future.

References (39)

  • WHO. Hepatitis B. Fact sheet No. 204, updated July 2015....
  • M.H. Chang

    Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan childhood hepatoma study group

    N Engl J Med

    (1997)
  • Y.H. Ni

    Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination

    Ann Intern Med

    (2001)
  • J. Simo Minana

    Hepatitis B vaccine immunoresponsiveness in adolescents: a revaccination proposal after primary vaccination

    Vaccine

    (1996)
  • W. Szmuness

    Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States

    N Engl J Med

    (1980)
  • E.A. Karlsson et al.

    The burden of obesity on infectious disease

    Exp Biol Med (Maywood)

    (2010)
  • B.M. Popkin et al.

    The obesity epidemic is a worldwide phenomenon

    Nutr Rev

    (1998)
  • M.L. Specchia

    Economic impact of adult obesity on health systems: a systematic review

    Eur J Publ Health

    (2015)
  • J. Ye et al.

    Inflammation during obesity is not all bad: evidence from animal and human studies

    Am J Physiol Endocrinol Metab

    (2013)

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    These authors contributed equally to this work.

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