ABSTRACT

Objective:

To estimate the prevalence and factors associated with hepatitis A, B, and C in transgender women and travestis's networks, in 5 regions of Brazil.

Methods:

This cross-sectional study includedtransgender women and travestis in five Brazilian capitals (Campo Grande, Manaus, Porto Alegre, Salvador, and São Paulo), between December/2019 and July/2021. All samples were subjected to detection of serological markers of hepatitis virus A (HAV), B (HBV), and C (HCV) infections through rapid tests and chemiluminescent microparticle immunoassays. Positive samples in the screening tests were submitted to detect HBV DNA and HCV-RNA by real-time PCR and genotyped by Sanger sequencing.

Results:

Analysis of 1,317 samples showed network prevalence rates of 69.1%, 25.1%, and 1.5% for HAV, HBV, and HCV exposure, respectively. A high susceptibility rate to HBV infection (35.7%) and low prevalence of vaccine response markers (40%) were also observed. Age greater than 26 years, self-declared black/brown skin color, having only primary education, history of incarceration, and use of a condom in the last sexual intercourse with a casual partner were associated with total anti-HAV. Exposure to HBV was associated with age greater than 26 years, self-declared black/brown, history of being a sex worker, and incarceration. Age > 37 years, history of sexual abuse, and frequent alcohol consumption were associated with hepatitis C infection.

Conclusion:

The highest prevalence of HAV in this population was found in the North and Northeast regions, and the prevalence found was higher than that in the general population, suggesting greater vulnerability. The prevalence of HCV infection in our study was similar to that observed in the general population.

Keywords:
Hepatitis A; Hepatitis B; Hepatitis C; Prevalence; Transgender women

INTRODUCTION

In 2016, the World Health Organization (WHO) proposed the elimination of viral hepatitis by 2030, urging countries to address key challenges such as reducing mortality, lowering incidence rates, improving diagnostic availability, and ensuring widespread access to treatment for the entire population¹1. World Health Organization. Global health sector strategy on viral hepatitis 2016-2021. Towards ending viral hepatitis [Internet]. Geneva: WHO; 2016 [cited on Feb 23, 2023]. Available at: https://apps.who.int/iris/handle/10665/246177
https://apps.who.int/iris/handle/10665/2... ,²2. World Health Organization. Global hepatitis reports, 2017 [Internet]. Geneva: WHO; 2017 [cited on Jan 15, 2023]. Available at: https://www.who.int/publications/i/item/9789241565455
https://www.who.int/publications/i/item/... .

Recent epidemiological studies focusing on key populations (gays and other men who have sex with men (MSM), transgender individuals, people who use alcohol and other drugs, individuals deprived of liberty, and sex workers) highlight the disproportionate burden of infections such as HIV, hepatitis B (HBV), hepatitis C (HCV), and other sexually transmitted infections (STIs)³3. Grinsztejn B, Jalil EM, Monteiro L, Velasque L, Moreira RI, Garcia ACF, et al. Unveiling of HIV dynamics among transgender women: a respondent-driven sampling study in Rio de Janeiro, Brazil. Lancet HIV 2017; 4(4): e169-e176. https://doi.org/10.1016/S2352-3018(17)30015-2.
https://doi.org/10.1016/S2352-3018(17)30... ,⁴4. Braga LP, Szwarcwald CL, Damacena GN. Caracterização de mulheres trabalhadoras do sexo em capitais brasileiras, 2016. Epidemiol Serv Saúde 2020; 29(4): e2020111. https://doi.org/10.5123/S1679-49742020000400002
https://doi.org/10.5123/S1679-4974202000... . Among these populations, transgender women and travestis are particularly at high risk of acquiring STIs such as HIV, syphilis, and hepatitis B⁵5. Veronese RT. Vulnerabilidades das travestis e das mulheres trans no contexto pandêmico. Rev Katál 2022; 25(2): 316-25. https://doi.org/10.1590/1982-0259.2022.e83737
https://doi.org/10.1590/1982-0259.2022.e... ,⁶6. Russi JC, Serra M, Viñoles J, Pérez MT, Ruchansky D, Alonso G, et al. Sexual transmission of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1 infections among male transvestite comercial sex workers in Montevideo, Uruguay. Am J Trop Med Hyg 2003; 68(6): 716-20. PMID: 12887033..

Leaving home/school early, discrimination and prejudice experienced by many of them, especially the poorest and the black, often lead them to social exclusion and, consequently, to prostitution as a survival strategy. Factors directly related to prostitution, such as risky sexual practices, a high number of sexual partners, consumption of illicit drugs and alcoholic beverages, low educational level, and socioeconomic marginalization, contribute to heightened vulnerability to acquiring STIs among this population⁵5. Veronese RT. Vulnerabilidades das travestis e das mulheres trans no contexto pandêmico. Rev Katál 2022; 25(2): 316-25. https://doi.org/10.1590/1982-0259.2022.e83737
https://doi.org/10.1590/1982-0259.2022.e...

6. Russi JC, Serra M, Viñoles J, Pérez MT, Ruchansky D, Alonso G, et al. Sexual transmission of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1 infections among male transvestite comercial sex workers in Montevideo, Uruguay. Am J Trop Med Hyg 2003; 68(6): 716-20. PMID: 12887033.-⁷7. Passos ADC, Figueiredo JFC. Fatores de risco para doenças sexualmente transmissíveis entre prostitutas e travestis de Ribeirão Preto (SP), Brasil. Rev Panam Salud Publica 2004; 16(2): 95-101. https://doi.org/10.1590/s1020-49892004000800004
https://doi.org/10.1590/s1020-4989200400... .

HAV infection is closely linked to hygiene conditions within the population and certain sexual practices. In particular, homeless women have a higher prevalence of HAV infection due to increased exposure to contaminated water and food, which facilitates the transmission of fecal-oral infections⁸8. Ferri LP, Junqueira PS, Almeida MMS, Oliveira MG, Oliveira BR, Silva BVD, et al. Viral hepatitis A, B and C in a group of transgender women in Central Brazil. Trop Med Infect Dis 2022; 7(10):269. https://doi.org/10.3390/tropicalmed7100269
https://doi.org/10.3390/tropicalmed71002... .

Vaccines against hepatitis A and B are widely available in Brazil. The hepatitis B vaccine has been administered since the 2000s and has progressively become accessible to adults up to 49 years of age. Initially, the hepatitis A vaccine was limited to individuals with serious conditions such as HIV, immunosuppression, or chronic carriers of hepatitis B and C⁸8. Ferri LP, Junqueira PS, Almeida MMS, Oliveira MG, Oliveira BR, Silva BVD, et al. Viral hepatitis A, B and C in a group of transgender women in Central Brazil. Trop Med Infect Dis 2022; 7(10):269. https://doi.org/10.3390/tropicalmed7100269
https://doi.org/10.3390/tropicalmed71002...

9. Ximenes RAA, Figueiredo GM, Cardoso MRA, Stein AT, Moreira RC, Coral GP, et al. Population-based multicentric survey of hepatitis B infection and risk factors in the North, South, and Southeast regions of Brazil, 10–20 years after the beginning of vaccination. Am J Trop Med Hyg 2015; 93(6): 1341-8. https://doi.org/10.4269/ajtmh.15-0216
https://doi.org/10.4269/ajtmh.15-0216... -¹⁰10. Pereira LMMB, Stein AT, Figueiredo GM, Coral GP, Montarroyos UR, Cardoso MRA, et al. Prevalence of hepatitis A in the capitals of the States of North, Southeast and South regions of Brazil: decrease in prevalence and some consequences. Rev Inst Med Trop São Paulo 2021; 63:e34. https://doi.org/10.1590/S1678-9946202163034
https://doi.org/10.1590/S1678-9946202163... . However, since 2014, it has been included in the National Vaccination Calendar and has been offered to all children from the age of 12 months. Regarding hepatitis C (HCV), the primary strategy involves early diagnosis of active infection, with effective treatment readily available within the public healthcare system, offering a high likelihood of cure for populations at a high risk of exposure to the virus¹¹11. Wolfe HL, Hughto JMW, Quint M, Hashemi L, Hughes LD. Hepatitis C virus testing and care cascade amongtransgender and gender diverse individuals. Am J Prev Med 2023; 64(5): 695-703. https://doi.org/10.1016/j.amepre.2023.01.005
https://doi.org/10.1016/j.amepre.2023.01...

12. Facente SN, Patel S, Hecht J, Wilson E, McFarland W, Page K, et al. Hepatitis C care cascades for 3 populations at high risk: low-income trans women, young people who inject drugs, and men who have sex with men and inject drugs. Clin Infect Dis 2021; 73(6): e1290-5. https://doi.org/10.1093/cid/ciab261
https://doi.org/10.1093/cid/ciab261... -¹³13. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para hepatite C e coinfecções [Internet]. Brasília: Ministério da Saúde; 2019 [cited on Feb 23, 2023]. Available at: https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/h/hepatites-virais/publicacoes/protocolo-clinico-e-diretrizes-terapeuticas-para-hepatite-c/view
https://www.gov.br/saude/pt-br/assuntos/... .

Based on the information provided, the objective of the present study was to determine the prevalence and factors associated with hepatitis A, B, and C among transgender women and travestis across five regions of Brazil, as well as to identify the genotypes or subtypes of hepatitis B virus (HBV) and hepatitis C virus (HCV) in this population.

METHODS

The current research is a component of the broader project titled “Study on the Prevalence of Syphilis and other Sexually Transmitted Infections (STIs) among Travestis and Transgender Women in Brazil: Care and Prevention.” It was conducted as a cross-sectional study across five major Brazilian cities (Campo Grande, Manaus, Porto Alegre, Salvador, and São Paulo), spanning from December 2019 to July 2021.

Participants were recruited using respondent-driven sampling (RDS). Upon signing the informed consent form, all participants were administered a questionnaire covering sociodemographic information, behavioral factors, and history of hepatitis A and B vaccination.

After completing the questionnaire, participants underwent venipuncture for blood collection to perform rapid tests (RT) for anti-HIV-1/2, anti-Treponema pallidum, HBV surface antigen (HBsAg), and anti-HCV. All blood samples were then sent to São Paulo, specifically to the Viral Hepatitis Laboratories of Instituto Adolfo Lutz (IAL) and the STI/AIDS Reference and Training Center (Centro de Referência e Treinamento em IST/Aids – CRT) for serological and molecular testing. The samples underwent detection of total anti-HAV, anti-HAV IgM, total anti-HBc, and anti-HBs using the chemiluminescent microparticle immunoassay (CMIA) technique, utilizing the Architect^® i1000 system (Abbott Ireland, Diagnostics Division, Sligo, Ireland), following the manufacturer’s instructions.

Samples that tested reactive for HBsAg (RT) and anti-HCV underwent detection and quantification of HBV DNA and HCV RNA using real-time PCR (qPCR) (Abbott^® Real Time, Des Plaines, USA). Genotyping of the samples with detected viral load was carried out using conventional PCR techniques, following protocols described by Sitnik et al.¹⁴14. Sitnik R, Pinho JRR, Bertollini DA, Bernardini AP, Silva LC, Carrilho FJ. Hepatitis B virus genotypes and precore and core mutants in Brazilian patients. J Clin Microbiol 2004; 42(6): 2455-60. https://doi.org/10.1128/JCM.42.6.2455-2460.2004
https://doi.org/10.1128/JCM.42.6.2455-24... and Gomes-Gouvêa et al.¹⁵15. Gomes-Gouvêa MS, Soares MCP, Bensabath G, Carvalho-Mello IMVG, Brito EMF, Souza OSC, et al. Hepatitis B virus and hepatitis delta virus genotypes in outbreaks of fulminant hepatitis (Labrea black fever) in the western Brazilian Amazon region. J Gen Virol 2009; 90(Pt 11): 2638-43. https://doi.org/10.1099/vir.0.013615-0
https://doi.org/10.1099/vir.0.013615-0... for HBV and, for HCV genotyping, Santos et al.¹⁶16. Santos APT, Silva VCM, Mendes-Corrêa MC, Lemos MF, Malta FM, Santana RAF, et al. Prevalence and pattern of resistance in NS5A/NS5B in hepatitis C chronic patients genotype 3 examined at a public health laboratory in the State of São Paulo, Brazil. Infect Drug Resist 2021; 14: 723-30. https://doi.org/10.2147/IDR.S247071
https://doi.org/10.2147/IDR.S247071... . The amplified genetic materials were sequenced using Sanger method¹⁷17. Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977; 74(12): 5463-7. https://doi.org/10.1073/pnas.74.12.5463
https://doi.org/10.1073/pnas.74.12.5463... , following the instructions in the package insert for the BigDye™ Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems, Foster City, CA, USA) and analyzed using the ABI3500 Automatic Sequencer (Applied Biosystems, Thermo Fisher Brand, Foster City, CA, USA). Genotypes were confirmed using the Geno2pheno¹⁸18. Kalaghatgi P, Sikorski AM, Knops E, Rupp D, Sierra S, Heger E, et al. Geno2pheno [HCV]: a web-based interpretation system to support hepatitis C treatment decisions in the era of direct-acting antiviral agents. PLoS One 2016; 11(5): e0155869. https://doi.org/10.1371/journal.pone.0155869
https://doi.org/10.1371/journal.pone.015... genotyping tool. Further methodological details of the study can be found in Veras et al.¹⁹19. Veras MASM, Pinheiro TF, Galan L, et al. TransOdara study: The challenge of integrating methods, settings and procedures during the COVID-19 pandemic in Brazil. Rev Bras Epidemiol. 2024; 27(Suppl 1): e240002.supl.1. https://doi.org/10.1590/1980-549720240002.supl.1
https://doi.org/10.1590/1980-54972024000...

The study outcomes comprised exposure to and presence of active disease from HAV, HBV, and HCV viruses. For HAV, exposure (HAV-Expo) was identified by total anti-HAV marker positivity, whereas the prevalence of active disease (HAV-Prev) was determined by the presence of the anti-HAV IgM marker. Regarding HBV, exposure (HBV-Expo) was ascertained by positivity for total anti-HBc and/or HBsAg, whereas active disease prevalence (HBV-Prev) was indicated by the presence of HBsAg associated with total anti-HBc. Participants with isolated positivity for anti-HBs (HBV-Vac) were considered immune due to hepatitis B vaccination, whereas those without any positive markers for HBV were classified as HBV “susceptible” to HBV infection (HBV-Susc). HCV exposure (HCV-Expo) was detected by anti-HCV positivity, whereas active disease prevalence (HCV-Prev) was determined by investigating the presence of HCV RNA viral load. The study included a total of 20 exposure variables potentially associated with each of the six outcomes mentioned above, based on the existing literature.

The main outcomes were presented as absolute and relative frequencies, along with a 95% confidence interval for the total sample and city/collection site. The exposure variables were also depicted in absolute and relative frequencies. Univariate logistic models were employed for the exploratory analysis of associations with each outcome. The selection of the final multivariate models began by identifying variables with a bivariate model p-value of 0.3²⁰20. Sperandei S. Understanding logistic regression analysis. Biochem Med (Zagreb) 2014; 24(1): 12-8. https://doi.org/10.11613/BM.2014.003
https://doi.org/10.11613/BM.2014.003... or less as candidates for inclusion. The GLMERSelect function from the “StatisticalModels” package in R, version 4.2²¹21. R Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2016 [cited on Feb 23, 2023]. Available at: https://www.R-project.org
https://www.R-project.org... , was used for stepwise selection of fixed effects and interactions in a generalized linear (logistic) mixed-effects model, with city/collection site as random intercepts. The results of the associations were presented as point odds ratios (OR) with their respective 95% confidence intervals.

The project was approved by the Research Ethics Committee of the Santa Casa de Misericórdia de São Paulo (CAAE 05585518.7.0000.5479; opinion n°: 3.126.815 – 30/01/2019), as well as by other participating institutions.

RESULTS

A total of 1,317 transgender women and travestis participated in the study, with 403 recruited in São Paulo, 192 in Porto Alegre, 201 in Salvador, 181 in Campo Grande, and 340 in Manaus. Across all five capitals, the mean age was 32.5 years (SD 10.0), with a median age of 31 years. The majority identified as transsexual women (66.8%), were single (70.1%), and reported completing or having incomplete high school education (54.3%). Regarding occupation, 24.6% reported being self-employed, 21.3% engaged in sex work, and 22.5% were unemployed at the time of the interview.

Tables 1 and 2 show the prevalence of serological markers of HAV, HBV, and HCV in the study population. The final number of samples analyzed varied according to each hepatitis and was lower than the number of samples collected due to the insufficient volume of serum/plasma/whole blood to carry out serological and/or molecular tests. A total of 1,270, 1,206, and 1,285 samples were analyzed to investigate serological markers of infections caused by HAV, HBV, and HCV, respectively.

Regarding markers for HAV, 877 participants (69.1%, 95%CI: 66.6–71.6) tested positive for total anti-HAV. The highest prevalence was observed in Manaus (80.3%), followed by São Paulo (71.3%), Campo Grande (65.1%), Salvador (58.8%), and Porto Alegre (57.4%). Anti-HAV IgM positivity was observed in 34 samples (2.7%, 95%CI: 1.8–3.6). The prevalence of active disease varied between 3% in Manaus and Campo Grande, 2.8% in Salvador, 2.7% in São Paulo, and 1.6% in Porto Alegre.

A total of 1,206 samples were tested for serological markers of HBV exposure. Among them, 294 tested positive for total anti-HBc and/or HBsAg, resulting in a prevalence of 24.4% (95%CI: 22.0–26.8). São Paulo (28.3%) and Porto Alegre (37.1%) had the highest rates of HBV exposure. HBsAg associated with total anti-HBc was detected in 22 participants, with only one showing isolated HBsAg. The presence of HBsAg in RT was observed in 1.8% of the samples (22/1,206; 95%CI: 1.2–2.7), ranging from 2.7% in Porto Alegre to 1.3% in Campo Grande. Total anti-HBc associated with anti-HBs was detected in 24.4% of the samples, and isolated anti-HBc was found in 3.4% of the samples.

Isolated positivity for the anti-HBs marker was observed in 40.0% of the participants (482/1,206), indicating a vaccine immune response to HBV. The highest rate was observed in São Paulo (47.8%), followed by Manaus (36.8%), Porto Alegre (36.6%), Salvador (36.3%), and Campo Grande (34.0%). Conversely, no serological marker for hepatitis B was detected in 35.7% of the samples (430/1, 206), suggesting susceptibility to HBV infection. The highest susceptibility rate to HBV infection was found in Manaus (48.4%), followed by Campo Grande (47.2%), Salvador (38.7%), Porto Alegre (26.3%), and São Paulo (23.8%).

Among the 22 samples that tested positive for HBsAg in RT, 19 underwent HBV DNA detection. HBV DNA was detected in 10 samples, and genotyping was performed on three of them. The genotypes identified were HBV-F (02/03) and HBV-A (01/03) (data not shown).

Serological markers of HCV exposure (anti-HCV) were detected in 1,285 blood samples. Among these, 19 samples tested positive for anti-HCV, resulting in a prevalence of 1.5% (95%CI 0.8–2.2). The prevalence rate of HCV exposure varied from 5.3% in Porto Alegre to 0.7% in São Paulo. No positive samples for anti-HCV were found in Salvador. Manaus and Campo Grande had anti-HCV antibody prevalence rates of 1.2% and 1.1%, respectively (Tables 1 and 2).

Nineteen samples positive for anti-HCV antibodies in the TR were sent to the IAL hepatitis laboratory for HCV RNA research. In three samples, it was not possible to perform the assay due to insufficient sample volume, and eight samples presented undetectable results. HCV RNA was detected in eight samples and was genotyped.

The most prevalent genotype was 3a, identified in 50.0% (04/08) of the samples, followed by genotype 1a, accounting for 25.0% (02/08), and genotype 1b, which also represented 25.0% (02/08) of the samples (data not shown).

The results of bivariate and multivariate analyses of factors associated with HAV, HBV, and HCV infections in the study population are presented in Supplementary Tables 1, 2, and 3, respectively. After multivariate analysis, for total anti-HAV positivity, the following variables remained associated: age over 26 years, self-identification as black/brown, only basic education, history of incarceration, and condom use in the last sexual intercourse with a casual partner. Protective factors included not having had sexual intercourse in the last six months and being homosexual, gay, or lesbian. Regarding HBV infection, the following variables were associated with the presence of serological markers after multivariate analysis: age over 26 years, self-identification as black/brown, involvement in sex work, being in a relationship, unstable housing (homeless or without a fixed address, shelter or institution, boarding house/hostel, or house of prostitution), and history of incarceration. However, history of sexual abuse was found to be a protective factor against HBV infection. For HCV infection, factors associated after multivariate analysis included age equal to or greater than 37 years, history of sexual abuse, and alcohol consumption four or more times a week.

DISCUSSION

The findings of the current study suggest that vaccination coverage against hepatitis A and B among the transgender women and travestis participants was low, despite the availability of these vaccines in the Brazilian Unified Health System (Sistema Único de Saúde – SUS)²²22. Brasil. Ministério da Saúde. Fundação Nacional de Saúde. Manual de preocedimentos de vacinação [Internet]. Brasília: Ministério da Saúde; 2001 [cited on Feb 23, 2023]. Available at: https://bvsms.saude.gov.br/bvs/publicacoes/funasa/manu_proced_vac.pdf
https://bvsms.saude.gov.br/bvs/publicaco... . This trend is consistent with previous research conducted in San Francisco, USA, by Choi et al.²³23. Choi KH, McFarland W, Neilands TB, Nguyen S, Secura G, Behel S, et al. High level of hepatitis B infection and ongoing risk among Asian/Pacific Islander men who have sex with men, San Francisco, 2000-2001. Sex Transm Dis 2005; 32(1): 44-8. https://doi.org/10.1097/01.olq.0000148296.93945.53
https://doi.org/10.1097/01.olq.000014829... , as well as studies conducted in Brazil by Rezende²⁴24. Rezende GR. Infecção pelo vírus da hepatite B em homens que fazem sexo com homens em Campo Grande-MS: aspectos epidemiológicos, moleculares e de vacina contra hepatite B [dissertação de mestrado]. Campo Grande: Universidade Federal de Mato Grosso do Sul (UFMS); 2014. and Oliveira et al.²⁵25. Oliveira MP, Matos MA, Silva AMC, Lopes CLR, Teles SA, Matos MA, et al. Prevalence, risk behaviors, and virological characteristics of hepatitis b virus infection in a group of men who have sex with men in brazil: results from a respondent-driven sampling survey. PLoS One. 2016; 11(8): e0160916. https://doi.org/10.1371/journal.pone.0160916
https://doi.org/10.1371/journal.pone.016... . These results underscore the vulnerability of the transgender women and travestis population to HBV infection and emphasize the importance of implementing strategies to raise awareness and enhance participation in vaccination programs.

The highest prevalence of confirmed hepatitis A in Brazil is concentrated in the North and Northeast regions, accounting for 55.4% of all cases, with the state of Amazonas exhibiting the highest prevalence of 8.35%²⁶26. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Boletim Epidemiológico. Hepatites virais 2022 [Internet]. Brasília: Ministério da Saúde; 2022 [cited on Feb 23, 2023]. Available at: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/especiais/2022/boletim-epidemiologico-de-hepatites-virais-2022-numero-especial/view
https://www.gov.br/saude/pt-br/centrais-... . Similarly, this study’s findings reflect this pattern, with Manaus showing the highest prevalence among the five participating cities, followed by São Paulo. The elevated prevalence observed in São Paulo may be attributed to a significant increase in hepatitis A cases during an outbreak among MSM and gay men within the same age group²⁵25. Oliveira MP, Matos MA, Silva AMC, Lopes CLR, Teles SA, Matos MA, et al. Prevalence, risk behaviors, and virological characteristics of hepatitis b virus infection in a group of men who have sex with men in brazil: results from a respondent-driven sampling survey. PLoS One. 2016; 11(8): e0160916. https://doi.org/10.1371/journal.pone.0160916
https://doi.org/10.1371/journal.pone.016... studied. This epidemic, occurring between 2016-2017, resulted in 155 hospitalizations, including four cases of fulminant hepatitis, two of which were fatal²⁷27. Divisão de Doenças de Transmissão Hídrica e Alimentar. Surto de Hepatite A no Estado de São Paulo, 2017. BEPA 2017; 14(165): 25-8..

A notably higher prevalence of total anti-HAV among black/brown transgender women is evident, which aligns with previous findings associating this demographic variable with the presence of an HAV infection marker²⁶26. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Boletim Epidemiológico. Hepatites virais 2022 [Internet]. Brasília: Ministério da Saúde; 2022 [cited on Feb 23, 2023]. Available at: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/especiais/2022/boletim-epidemiologico-de-hepatites-virais-2022-numero-especial/view
https://www.gov.br/saude/pt-br/centrais-... . It is crucial to highlight that black transgender/travestis individuals tend to initiate sexual activity earlier than their white counterparts and report higher incidences of sexual violence during childhood and adolescence, as well as experiences of homelessness, factors that increase their exposure and susceptibility to fecal-oral infections²⁷27. Divisão de Doenças de Transmissão Hídrica e Alimentar. Surto de Hepatite A no Estado de São Paulo, 2017. BEPA 2017; 14(165): 25-8.,²⁸28. Menezes LMJ. Vulnerabilidades de saúde e sexuais de mulheres transexuais e travestis negras. BIS 2021; 22(1): 97-111.. These findings are consistent with data from previous studies, such as that by Castro et al.²⁹29. Castro LS, Rezende GR Fernandes FRP, Bandeira LM, Cesar GA, Lago BV, et al. HAV infection in Brazilian men who have sex with men: the importance of surveillance to avoid outbreaks. PLoS One 2021; 16(9): e0256818. https://doi.org/10.1371/journal.pone.0256818
https://doi.org/10.1371/journal.pone.025... , who observed a prevalence of 69.7% among transgender women in the Central-West region of Brazil. Given that the population in this study was over 18 years old and, as already described in the literature³⁰30. Migueres M, Lhomme S, Izopet J. Hepatitis A: epidemiology, high-risk groups, prevention and research on antiviral treatment. Viruses 2021; 13(10): 1900. https://doi.org/10.3390/v13101900
https://doi.org/10.3390/v13101900... , cases of acute infection in adults may present with more severe clinical manifestations. Vaccination against hepatitis A in the transgender women and travestis population and the promotion of safe sex practices, including the use of condoms during oral-anal sex, are essential preventive measures to mitigate the risk of hepatitis A transmission.

Additionally, there is a finding that contradicts plausibility and the literature⁸8. Ferri LP, Junqueira PS, Almeida MMS, Oliveira MG, Oliveira BR, Silva BVD, et al. Viral hepatitis A, B and C in a group of transgender women in Central Brazil. Trop Med Infect Dis 2022; 7(10):269. https://doi.org/10.3390/tropicalmed7100269
https://doi.org/10.3390/tropicalmed71002... ,²⁷27. Divisão de Doenças de Transmissão Hídrica e Alimentar. Surto de Hepatite A no Estado de São Paulo, 2017. BEPA 2017; 14(165): 25-8.. Exposure to sexual violence appeared to be a protective factor in the present study, similar to the association of hepatitis A with the use of condoms in the last relationship. These associations may be confounded by unmeasured factors.

With regard to hepatitis B, the global prevalence of markers of exposure to HBV found in this study, in the transgender women and travestis studied, was higher than that found in the population-based survey, carried out between 2005 and 2009, in the 26 capitals and the Federal District (7.4%; 95%CI 6.8–8.0), suggesting greater vulnerability of this population to HBV infection³¹31. Pereira LMMB, Martelli CMT, Moreira RC, Merchan-Hamman E, Stein AT, Cardoso MRA, et al. Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study. BMC Infect Dis 2013; 13: 60. https://doi.org/10.1186/1471-2334-13-60
https://doi.org/10.1186/1471-2334-13-60... . However, it was similar to that found in Central-West Brazil in 2018²⁴24. Rezende GR. Infecção pelo vírus da hepatite B em homens que fazem sexo com homens em Campo Grande-MS: aspectos epidemiológicos, moleculares e de vacina contra hepatite B [dissertação de mestrado]. Campo Grande: Universidade Federal de Mato Grosso do Sul (UFMS); 2014. and lower than the prevalence found in other Latin American countries such as Argentina³²32. Ramos Farías MS, Garcia MN, Reynaga E, Romero M, Gallo Vaulet ML, Rodriguez Fermepín M, et al. First report on sexually transmitted infections among trans (male to female , transsexuals, or transgender) and male sex workers in Argentina: high HIV, HPV, HBV, and syphilis prevalence. Int J Infect Dis 2011; 15(9): E635-40. https://doi.org/10.1016/j.ijid.2011.05.007
https://doi.org/10.1016/j.ijid.2011.05.0... (40.2 %) and Uruguay⁶6. Russi JC, Serra M, Viñoles J, Pérez MT, Ruchansky D, Alonso G, et al. Sexual transmission of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1 infections among male transvestite comercial sex workers in Montevideo, Uruguay. Am J Trop Med Hyg 2003; 68(6): 716-20. PMID: 12887033. (50.5 %).

The HBsAg positivity observed in the transgender women and travestis studied was higher than the prevalence of HBsAg found in the population-based study carried out in Brazilian capitals³⁰30. Migueres M, Lhomme S, Izopet J. Hepatitis A: epidemiology, high-risk groups, prevention and research on antiviral treatment. Viruses 2021; 13(10): 1900. https://doi.org/10.3390/v13101900
https://doi.org/10.3390/v13101900... . It was also similar to that found in Argentina (1.9%)32 and in Campo Grande-MS (2.7%)²⁴24. Rezende GR. Infecção pelo vírus da hepatite B em homens que fazem sexo com homens em Campo Grande-MS: aspectos epidemiológicos, moleculares e de vacina contra hepatite B [dissertação de mestrado]. Campo Grande: Universidade Federal de Mato Grosso do Sul (UFMS); 2014. in transgender people and sex workers. However, it was lower than the rates found in countries such as Pakistan³³33. Baqi S, Shah SA, Baig MA, Mujeeb SA, Memon A. Seroprevalence of HIV, HBV, and syphilis and associated risk behaviours in male (Hijras) in Karachi, Pakistan. Int J STD AIDS 1999; 10(5): 300-4. https://doi.org/10.1258/0956462991914159
https://doi.org/10.1258/0956462991914159... (3.4%) and Uruguay⁶6. Russi JC, Serra M, Viñoles J, Pérez MT, Ruchansky D, Alonso G, et al. Sexual transmission of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1 infections among male transvestite comercial sex workers in Montevideo, Uruguay. Am J Trop Med Hyg 2003; 68(6): 716-20. PMID: 12887033. (3.0%).

Multivariate analysis revealed that age > 26 years was independently associated with HBV infection. This association is likely due to the increased risk of viral exposure over the course of one’s lifetime, particularly through sexual contact, a pattern consistent with previous research findings³⁴34. Pitasi MA, Bingham TA, Sey EK, Smith AJ, Teshale EH. Hepatitis B virus (HBV) infection, immunity and susceptibility among men who have sex with men (MSM), Los Angeles County, USA. AIDS Behav 2014; 18 Suppl 3: 248-55. https://doi.org/10.1007/s10461-013-0670-2
https://doi.org/10.1007/s10461-013-0670-... ,³⁵35. Linkins RW, Chonwattana W, Holtz TH, Wasinrapee P, Chaikummao S, Varangrat A, et al. Hepatitis A and hepatitis B infection prevalence and associated risk factors in men who have sex with men, Bangkok, 2006–2008. J Med Virol 2013; 85(9): 1499-505. https://doi.org/10.1002/jmv.23637
https://doi.org/10.1002/jmv.23637... . Additionally, engagement in sex work, either currently or in the past, has emerged as another factor linked to hepatitis B infection in this population, as has been observed in other studies³⁵35. Linkins RW, Chonwattana W, Holtz TH, Wasinrapee P, Chaikummao S, Varangrat A, et al. Hepatitis A and hepatitis B infection prevalence and associated risk factors in men who have sex with men, Bangkok, 2006–2008. J Med Virol 2013; 85(9): 1499-505. https://doi.org/10.1002/jmv.23637
https://doi.org/10.1002/jmv.23637...

36. Gorgos L. Sexual transmission of viral hepatitis. Infect Dis Clin North Am 2013; 27(4): 811-36. https://doi.org/10.1016/j.idc.2013.08.002
https://doi.org/10.1016/j.idc.2013.08.00... -³⁷37. Lama JR, Agurto HS, Guanira JV, Ganoza C, Casapia M, Ojeda N, et al. Hepatitis B infection and association with other sexually transmitted infections among men who have sex with men in Peru. Am J Trop Med Hyg 2010; 83(1): 194-200. https://doi.org/10.4269/ajtmh.2010.10-0003
https://doi.org/10.4269/ajtmh.2010.10-00... . Notably, a significant proportion of the studied population reported either current or past involvement in sex work, a trend consistent with prior studies⁷7. Passos ADC, Figueiredo JFC. Fatores de risco para doenças sexualmente transmissíveis entre prostitutas e travestis de Ribeirão Preto (SP), Brasil. Rev Panam Salud Publica 2004; 16(2): 95-101. https://doi.org/10.1590/s1020-49892004000800004
https://doi.org/10.1590/s1020-4989200400... ,²⁴24. Rezende GR. Infecção pelo vírus da hepatite B em homens que fazem sexo com homens em Campo Grande-MS: aspectos epidemiológicos, moleculares e de vacina contra hepatite B [dissertação de mestrado]. Campo Grande: Universidade Federal de Mato Grosso do Sul (UFMS); 2014.,³⁸38. Martins TA, Kerr LRFS, Macena RHM, Mota RS, Carneiro KL, Gondim RC, et al. Travestis, an unexplored population at risk of HIV in a large metropolis of northeast Brazil: a respondent-driven sampling survey. AIDS Care 2013; 25(5): 606-12. https://doi.org/10.1080/09540121.2012.726342
https://doi.org/10.1080/09540121.2012.72... . Research has indicated that factors such as financial needs, social stigma, limited employment opportunities, and marginalization in healthcare contribute to transgender individuals’ engagement in sex work³⁹39. Sausa LA, Keatley J, Operario D. Perceived risks and benefits of sex work among transgender women of color in San Francisco. Arch Sex Behav 2007; 36(6): 768-77. https://doi.org/10.1007/s10508-007-9210-3
https://doi.org/10.1007/s10508-007-9210-... ,⁴⁰40. Reisner SL, Mimiaga MJ, Bland S, Mayer KH, Perkovich B, Safren SA. HIV risk and social networks among male-to-female transgender sex workers in Boston, Massachusetts. J Assoc Nurses AIDS Care 2009; 20(5): 373-86. https://doi.org/10.1016/j.jana.2009.06.003
https://doi.org/10.1016/j.jana.2009.06.0... . Such circumstances predispose them to increased risk of contracting STIs, including HBV, attributed to factors like having multiple sexual partners and engaging in risky sexual behaviors³⁴34. Pitasi MA, Bingham TA, Sey EK, Smith AJ, Teshale EH. Hepatitis B virus (HBV) infection, immunity and susceptibility among men who have sex with men (MSM), Los Angeles County, USA. AIDS Behav 2014; 18 Suppl 3: 248-55. https://doi.org/10.1007/s10461-013-0670-2
https://doi.org/10.1007/s10461-013-0670-... ,³⁸38. Martins TA, Kerr LRFS, Macena RHM, Mota RS, Carneiro KL, Gondim RC, et al. Travestis, an unexplored population at risk of HIV in a large metropolis of northeast Brazil: a respondent-driven sampling survey. AIDS Care 2013; 25(5): 606-12. https://doi.org/10.1080/09540121.2012.726342
https://doi.org/10.1080/09540121.2012.72... ,⁴¹41. Setia MS, Lindan C, Jerajani HR, Kumta S, Ekstrand M, Mathur M, et al. Men who have sex with men and transgenders in Mumbai, India: an emerging risk group for STIs and HIV. Indian J Dermatol Venereol Leprol 2006; 72(6): 425-31. https://doi.org/10.4103/0378-6323.29338
https://doi.org/10.4103/0378-6323.29338... .

Socioeconomic factors, including unstable housing conditions, have been identified as significant contributors to HBV exposure. Previous research conducted in Brazil⁷7. Passos ADC, Figueiredo JFC. Fatores de risco para doenças sexualmente transmissíveis entre prostitutas e travestis de Ribeirão Preto (SP), Brasil. Rev Panam Salud Publica 2004; 16(2): 95-101. https://doi.org/10.1590/s1020-49892004000800004
https://doi.org/10.1590/s1020-4989200400... ,²⁴24. Rezende GR. Infecção pelo vírus da hepatite B em homens que fazem sexo com homens em Campo Grande-MS: aspectos epidemiológicos, moleculares e de vacina contra hepatite B [dissertação de mestrado]. Campo Grande: Universidade Federal de Mato Grosso do Sul (UFMS); 2014.,³⁸38. Martins TA, Kerr LRFS, Macena RHM, Mota RS, Carneiro KL, Gondim RC, et al. Travestis, an unexplored population at risk of HIV in a large metropolis of northeast Brazil: a respondent-driven sampling survey. AIDS Care 2013; 25(5): 606-12. https://doi.org/10.1080/09540121.2012.726342
https://doi.org/10.1080/09540121.2012.72... and India⁴¹41. Setia MS, Lindan C, Jerajani HR, Kumta S, Ekstrand M, Mathur M, et al. Men who have sex with men and transgenders in Mumbai, India: an emerging risk group for STIs and HIV. Indian J Dermatol Venereol Leprol 2006; 72(6): 425-31. https://doi.org/10.4103/0378-6323.29338
https://doi.org/10.4103/0378-6323.29338... has also highlighted the low socioeconomic status prevalent among transgender women. This socioeconomic status often correlates with precarious housing conditions characterized by inadequate hygiene, sanitation, and increased exposure to violence, all of which elevate the risk of infection transmission.

Hepatitis C is important in the population of transgender women, mainly due to transmission through the use of injectable and/or inhalable drugs; people deprived of liberty; and people infected with HIV¹²12. Facente SN, Patel S, Hecht J, Wilson E, McFarland W, Page K, et al. Hepatitis C care cascades for 3 populations at high risk: low-income trans women, young people who inject drugs, and men who have sex with men and inject drugs. Clin Infect Dis 2021; 73(6): e1290-5. https://doi.org/10.1093/cid/ciab261
https://doi.org/10.1093/cid/ciab261... . The highest detection rate of HCV was found in the capital of Rio Grande do Sul, the state with the highest rate of infection in the country²⁶26. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Boletim Epidemiológico. Hepatites virais 2022 [Internet]. Brasília: Ministério da Saúde; 2022 [cited on Feb 23, 2023]. Available at: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/especiais/2022/boletim-epidemiologico-de-hepatites-virais-2022-numero-especial/view
https://www.gov.br/saude/pt-br/centrais-... . However, overall, the prevalence of HCV in the study population was similar to that found in the general population, which, according to the national survey, was 1.38%³¹31. Pereira LMMB, Martelli CMT, Moreira RC, Merchan-Hamman E, Stein AT, Cardoso MRA, et al. Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study. BMC Infect Dis 2013; 13: 60. https://doi.org/10.1186/1471-2334-13-60
https://doi.org/10.1186/1471-2334-13-60... .

The prevalence of HCV within the studied group contrasts notably with findings from the USA. Two RDS studies conducted with transgender women in California in 2017 and 2020 reported prevalence rate of 23.8% and 23.9%, respectively⁴²42. Wilson EC, Turner C, Lin J, McFarland W, Burk K, Raymond HF. Hepatitis C seroprevalence and engagement in related care and treatment among trans women. J Viral Hepat 2019; 26(7): 923-5. https://doi.org/10.1111/jvh.13089
https://doi.org/10.1111/jvh.13089... ,⁴³43. Hernandez CJ, Trujillo D, Sicro S, Meza J, Bella M, Daza E, et al. High hepatitis C virus seropositivity, viremia, and associated risk factors among trans women living in San Francisco, California. PLoS One 2021; 16(3): e0249219. https://doi.org/10.1371/journal.pone.0249219
https://doi.org/10.1371/journal.pone.024... . Additionally, the association of age as a risk factor for HCV, already described in the literature³²32. Ramos Farías MS, Garcia MN, Reynaga E, Romero M, Gallo Vaulet ML, Rodriguez Fermepín M, et al. First report on sexually transmitted infections among trans (male to female , transsexuals, or transgender) and male sex workers in Argentina: high HIV, HPV, HBV, and syphilis prevalence. Int J Infect Dis 2011; 15(9): E635-40. https://doi.org/10.1016/j.ijid.2011.05.007
https://doi.org/10.1016/j.ijid.2011.05.0... , appears in both Brazilian and American contexts.

The association between HCV infection and alcohol consumption, as well as a history of sexual abuse, may stem from broader repercussions of violence against women or children. Such experiences often result in various psychological and behavioral impacts on the victim, increasing the likelihood of engaging in alcohol and/or drug use in the future⁴⁴44. Gebara CFP, Lourenco LM. Crenças de profissionais da saúde sobre violência doméstica contra crianças e adolescentes. Psicol Pesq 2008; 2(1): 27-39.,⁴⁵45. Krug EG, Dahlberg LL, Mercy JA, Zwi A, Lozano R. World report on violence and health [Internet]. Geneva: WHO; 2022 [cited on Dec 11, 2023]. Available at: https://iris.who.int/bitstream/handle/10665/42495/9241545615_eng.pdf?sequence=1
https://iris.who.int/bitstream/handle/10... .

This study has several limitations. Given its cross-sectional nature, establishing a causal relationship between the analyzed exposure variables and outcomes is not feasible. Additionally, susceptibility rates and the presence of markers indicating a response to hepatitis B vaccination may have been underestimated, as the levels of anti-HBs antibodies diminish over time and can become undetectable. Memory bias and reliance on self-reporting also represent notable limitations. Moreover, the financial incentives associated with the recruitment method might have biased the participation of predominantly low-income transgender women and travestis in the study.

The WHO acknowledges that certain key populations, including transgender individuals, exhibit higher prevalence rates of viral hepatitis compared to the general population. Understanding the epidemiological and molecular aspects of hepatitis A, B, and C within these groups, such as transgender women and travestis, is crucial for informing public health policies tailored to their needs¹1. World Health Organization. Global health sector strategy on viral hepatitis 2016-2021. Towards ending viral hepatitis [Internet]. Geneva: WHO; 2016 [cited on Feb 23, 2023]. Available at: https://apps.who.int/iris/handle/10665/246177
https://apps.who.int/iris/handle/10665/2... . The data presented underscores the significant impact of viral hepatitis on this population, characterized by heightened vulnerability due to factors such as inconsistent adoption of safe sexual practices, history of STIs, social stigma, violence, and barriers to accessing healthcare services. These findings emphasize the importance of targeted public policies aimed at this key population, with a focus on enhancing vaccination coverage, and facilitating access to testing and treatment services.

ACKNOWLEDGMENTS:

We gratefully acknowledge the financial support provided by the Ministry of Health/PAHO; Instituto Adolfo Lutz, São Paulo, Brazil; STD/AIDS Reference and Training Center – São Paulo State Health Secretariat, São Paulo, Brazil.

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