Tengan et al. BMC Infectious Diseases (2017) 17:587 DOI 10.1186/s12879-017-2695-z RESEARCHARTICLE Open Access Prevalence of hepatitis B in people living with HIV/AIDS in Latin America and the Caribbean: a systematic review and meta-analysis Fatima Mitiko Tengan1,2*, Edson Abdala1,2, Marisa Nascimento3, Wanderley Marques Bernardo4,5 and Antonio Alci Barone1,2 Abstract Background: Hepatitis B virus (HBV) infection is a major cause of chronic liver disease worldwide. In immunocompromised patients, the chronicity rates of HBV infection are higher, but the rates of hepatitis Be antigen (HBeAg) and HBsAg loss and seroconversion to anti-HBe and anti-HBs are lower than those in immunocompetent subjects. This study aimed to evaluate articles on the prevalence of HBsAg in people living with human immunodeficiency virus (HIV) /AIDS (PLWHA) in Latin America and the Caribbean (LAC). Methods: We searched the PubMed, Latin American and Caribbean Health Sciences, and Embase databases for studies up to November 2016 on infection with HIV and HBV in LAC without period or language restrictions. We did not include case reports, case series, review articles, comments, or studies with a sample size smaller than 100. We also evaluated the quality of the articles using a list of criteria totaling 21 items. Results: Of the 28 selected articles (n = 18,457) published from 1999 to 2016, 18 studies (64.3%) were from Brazil, 3 (10.7%) were from Argentina, 2 (7.1%) were from Chile, 2 (7.1%) were from Cuba, 1 (3.6%) was from Colombia, 1 (3.6%) was from Venezuela, and 1 (3.6%) was from Jamaica. The mean score for the assessment of the study quality was 11.6 (range: 8–16). The estimated pooled prevalence of HBsAg among PLWHA in the selected studies was 7.0% (95% CI 7.0–7.0%). The pooled prevalence of HBsAg was 8.0% (95% CI 8.0–9.0%) in the studies published from 1999 to 2006 and 6.0% (95% CI 5.0–6.0%) in the studies published during the later timeframe. Conclusions: The results of this review indicate the need to increase the investment in preventive measures against hepatitis B, particularly when the impact of adequate vaccination in this population is considered. Future studies with larger sample sizes are needed in LAC to determine the true prevalence of hepatitis B throughout the region and to clarify and address the risk factors associated with the acquisition of infection. Keywords: Hepatitis B, Hepatitis B virus, HIV, Human immunodeficiency virus, Latin America, The Caribbean, Prevalence, Systematic review, Review * Correspondence: [email protected] 1Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo (Universidade de São Paulo - USP), São Paulo, Brazil 2Laboratory of Viral Medical Research in Hepatology (Laboratório de Investigação Médica em Hepatologia por vírus - LIM-47), Clinical Hospital, School of Medicine, USP, São Paulo, Brazil Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Tengan et al. BMC Infectious Diseases (2017) 17:587 Page 2 of 10 Background Search strategies Hepatitis B virus (HBV) infection is a major cause of We searched Medline via the PubMed, Latin American chronic liver disease worldwide, and approximately 350 and Caribbean Health Sciences (Literatura Latino- million people are chronically infected. In the absence of Americana e do Caribe em Ciências da Saúde–Lilacs) antiviral therapy, 15% to 40% of patients positive for the via BVS, and Embase databases for studies up to hepatitis B surface antigen (HBsAg) develop progressive November 2016 on infection with HIV and HBV in LAC liver disease, cirrhosis, hepatocellular carcinoma, and without period and language restrictions. In Medline, we terminal liver failure [1]. Because HBV is primarily used the terms [(HIV OR Acquired Immunodeficiency transmitted via the parenteral and sexual routes and Syndrome Virus OR AIDS OR HTLV OR Human during the perinatal period similar to human immuno- Immunodeficiency Virus OR Human TCell) AND deficiency virus (HIV), coinfection with HIV and HBV is (HBV OR Hepatitis B OR Hepatitis B Virus) AND common [2]. (name of each country or territory from LAC)]. In HIV infection appears to have a negative impact on Lilacs, we used the terms [(HIV OR AIDS OR the natural history of HBV infection. In immunocom- HUMAN IMMUNODEFICIENCY VIRUS) [Words] promised patients, the chronicity rates of HBV infection AND (HBV OR HEPATITIS B) [Words]]. In Embase, are higher, but the rates of hepatitis Be antigen (HBeAg) we searched the terms [(HIV OR AIDS OR HUMAN and HBsAg loss and seroconversion to anti-HBe and IMMUNODEFICIENCY VIRUS) AND (HBV OR anti-HBs are lower than those in immunocompetent HEPATITIS B)]. We manually searched the references subjects [3–5]. of the selected studies and reviewed articles on the Patients with HIV infection have lower serum alanine subjects to identify other relevant studies. Disagree- aminotransferase and albumin levels and higher serum ments on the identification of relevant studies were HBV DNA levels than patients with HBV monoinfec- discussed until a consensus was reached. tion. Additionally, the prevalence of cirrhosis is higher in The studies eligible for reading of the titles and ab- HIV-positive patients [6]. Coinfection with HIV and stracts were selected independently by two researchers HBV is associated with a higher rate of HBV reactivation (E.A. and M.N.), and a list of potentially relevant studies and an increased incidence of cirrhosis and death from was generated. Articles for inclusion in the review were cirrhosis in cases with low CD4 counts. Coinfection is selected after reading the full text (A.A.B. and W.M.B.). also associated with a higher incidence of hepatocellular The articles included were those that contained data carcinoma [7, 8]. on HBV infection in PLWHA, a serological diagnosis of Other studies have suggested that HBV is associated HIV and HBV, and estimates of the prevalence of HBsAg with a rapidly progressive course of HIV infection [9]. A in HIV-infected individuals. retrospective analysis indicated that the risk of death in 64 individuals coinfected with HIV and HBV was ap- Study selection proximately two-fold higher than that in individuals with We included original articles that reported the preva- HIV monoinfection [10]. lence of HBV in PLWHA in LAC with a sample size The estimated prevalence of hepatitis B among people ≥100. We did not include case reports, case series, re- living with HIV/AIDS (PLWHA) is 5–20%. Therefore, view articles, comments, studies whose participants did approximately 2 to 4 million people living with HIV not live in LAC, or studies that contained the same case have chronic hepatitis B coinfection [2, 11]. Although series presented in other publications. Regarding the lat- several studies have evaluated the prevalence of hepatitis ter studies, the article with the most complete data was B in PLWHA in Latin America and the Caribbean included in the study. We excluded self-reported HIV (LAC), the results are conflicting among the evaluated and/or HBV infections, data obtained from mandatory regions and even within the same geographic area. This reporting of HIV and/or HBV (e.g., databases of the local study aimed to evaluate the studies on the prevalence of Ministry of Health), and studies whose participant selec- HBsAg in LAC countries or territories. tion method was unclear. We used the following definitions: (1) HIV infection: Methods the presence of anti-HIV antibodies measured by en- We conducted a systematic review of published articles zyme immunoassay; (2) HBV infection: the presence of on the prevalence of HBV infection in PLWHA in LAC HBsAg; and (3) Latin America and the Caribbean: the countries or territories. Our review was conducted and countries and territories of Argentina, Bolivia, Brazil, reported in accordance with the Preferred Reporting Chile, Colombia, Ecuador, French Guiana, Guyana, Items for Systematic Reviews and Meta-Analyses Paraguay, Peru, Suriname, Uruguay, Venezuela, Belize, (PRISMA) Statement published in 2009 [12] (Additional Costa Rica, El Salvador, Guatemala, Honduras, Mexico, file 1). Nicaragua, Panama, Aruba, Antigua and Barbuda, Tengan et al. BMC Infectious Diseases (2017) 17:587 Page 3 of 10 Aruba, Bahamas, Barbados, Bonaire, British Virgin Laird method, which took into account variation among Islands, Cayman Islands, Cuba, Curaçao, Dominica, studies. Heterogeneity was assessed using Cochran’sQ Dominican Republic, Grenada, Guadalupe, Haiti, statistic (expressed as χ2 and p values) and the I2 statis- Jamaica, Martinique, Montserrat, Puerto Rico, Saba, tic, which described the percentage of variation among Saint Barthelemy, Saint Kitts and Nevis, Saint Lucia, studies explained by heterogeneity rather than by Saint Martin, Saint Vincent and The Grenadines, Sint chance. I2 values higher than 25%, 50%, and 75% are Eustatius, Sint Maarten, Trinidad and Tobago, Turks and considered evidence of low, moderate, and high hetero- Caicos Islands, and the United States Virgin Islands. geneity among studies, respectively. Low I2 values indi- cate that the variability among estimates is compatible Data extraction with random variation. Additionally, we investigated po- Data were collected independently by two investigators tential sources of heterogeneity using a meta-regression (A.A.B. and W.M.B.), and disagreements were resolved analysis. The following factors were assessed using both via discussions and a consensus.