Severe cases of hepatitis A: case series in Curitiba, Paraná, 2023-2024Abstract
Objective: Describe the epidemiological profile of the hepatitis A outbreak in Curitiba, Paraná, between November 2023 and May 2024, with emphasis on the clinical and laboratory characterization of cases that progressed to death or liver transplantation.
Methods: Descriptive case series study based on confirmed cases of hepatitis A. Severe cases, defined by death or liver transplantation, were identified via the Mortality Information System and Hospital Epidemiological Surveillance Centers. Clinical and laboratory data were obtained by reviewing medical records. Proportions, measures of central tendency, and dispersion were calculated.
Results: Among the 281 confirmed cases, the majority were male (74.7%), with a median age of 29 years. Six people (2.1%) progressed to severe forms, of whom three received a diagnosis of fulminant hepatitis. The median age of the severe cases was 43 years, with a male predominance (5/6), and two were homeless individuals. Among the severe cases, five resulted in death, and one in a liver transplant. The most common symptoms and complications were jaundice, acute renal failure, and the need for mechanical ventilation (5/6). Laboratory results indicated hepatic dysfunction (median aspartate aminotransferase of 3,448 U/L; median international normalized ratio of 3) and renal dysfunction (median urea 52 mg/dL and creatinine 3 mg/dL). The median hospitalization length was 11 days.
Conclusion: In this outbreak, there were cases requiring liver transplantation and progressing to death, demonstrating that, although generally self-limiting, the disease can present with a severe course. Timely response and targeted vaccination may be key strategies in outbreak scenarios.
Keywords:
Hepatitis; Hepatitis A Virus; Acute Liver Failure; Liver Failure; Descriptive Studies.
Resumo
Objetivo: Descrever o perfil epidemiológico do surto de hepatite A em Curitiba, Paraná, entre novembro de 2023 e maio de 2024, com ênfase na caracterização clínica e laboratorial dos casos que evoluíram para óbito ou transplante hepático.
Métodos: Estudo descritivo tipo série de casos baseado em casos confirmados de hepatite A. Casos graves, definidos por óbito ou transplante hepático, foram identificados via Sistema de Informação sobre Mortalidade e Núcleos Hospitalares de Vigilância Epidemiológica. Dados clínico-laboratoriais foram obtidos por revisão de prontuários. Calcularam-se proporções, medidas de tendência central e dispersão.
Resultados: Entre os 281 casos confirmados, a maioria era do sexo masculino (74,7%), com idade mediana de 29 anos. Seis pessoas (2,1%) evoluíram para formas graves, dos quais três receberam diagnóstico de hepatite fulminante. A mediana de idade dos casos graves foi de 43 anos, predominância masculina (5/6) e dois eram pessoas em situação de rua. Entre os casos graves, cinco foram óbitos e um transplante hepático. Os sintomas e complicações mais comuns foram icterícia, insuficiência renal aguda e necessidade de ventilação mecânica (5/6). Resultados laboratoriais indicaram disfunção hepática (transaminase glutâmico-oxalacética mediana de 3.448 U/L; razão normalizada internacional mediana de 3) e disfunção renal (mediana de ureia 52 mg/dL e de creatinina 3 mg/dL). A mediana de hospitalização foi de 11 dias.
Conclusão: Nesse surto ocorreram casos com necessidade de transplante hepático e evolução para óbito, evidenciando que, embora geralmente autolimitada, a doença pode apresentar evolução grave. A resposta oportuna e a vacinação direcionada podem ser estratégias-chave em cenários de surto.
Palavras-chave:
Hepatite; Vírus da Hepatite A; Insuficiência Hepática Aguda; Falência Hepática; Estudos Descritivos.
Resumen
Objetivo: Describir el perfil epidemiológico del brote de hepatitis A en Curitiba, Paraná (Brasil), entre noviembre de 2023 y mayo de 2024, con énfasis en la caracterización clínica y de laboratorio de los casos que evolucionaron a muerte o a trasplante hepático.
Métodos: Estudio descriptivo, de tipo serie de casos, basado en casos confirmados de hepatitis A. Los casos graves definidos por muerte o trasplante hepático se identificaron en el Sistema de Información de Mortalidad y en los Centros de Vigilancia Epidemiológica Hospitalaria. Los datos clínicos y de laboratorio se obtuvieron mediante una búsqueda en los registros médicos. Se calcularon proporciones, medidas de tendencia central y dispersión.
Resultados: Entre los 281 casos confirmados, la mayoría fueron hombres (74,7%), con una mediana de edad de 29 años. Seis personas (2,1%) progresaron a cuadros graves, de las cuales tres tuvieron diagnóstico de hepatitis fulminante. La mediana de edad de los casos graves fue de 43 años, con predominio de hombres (5/6), y dos casos eran de personas sin hogar. Entre los casos graves, cinco fueron muertes y un trasplante de hígado. Los síntomas y las complicaciones más comunes fueron ictericia, insuficiencia renal aguda y necesidad de ventilación mecánica (5/6). Los resultados de laboratorio indicaron disfunción hepática (mediana de transaminasa glutámico-oxalacética de 3.448 U/L; mediana de la razón internacional normalizada de 3) y disfunción renal (mediana de urea 52 mg/dL y creatinina 3 mg/dL). La estancia hospitalaria media fue de 11 días.
Conclusión: En este brote, hubo casos que requirieron trasplante hepático y que tuvieron progresión a muerte, lo que demuestra que, aunque generalmente autolimitada, la enfermedad puede presentar una evolución severa. La respuesta oportuna y la vacunación adecuada pueden ser estrategias clave en los escenarios de brotes.
Palabras clave:
Hepatitis; Virus de la Hepatitis A; Fallo hepático agudo; Fallo Hepático; Estudios Descriptivos.
Ethical aspects
This research respected the ethical principles, having obtained the following approval data:
Research Ethics Committee: National Ethics Committee for Research
Opinion number: 7,545,013
Approval date: 13/6/2025
Certificate of Submission for Ethical Appraisal: 87956525.0.0000.0008
Informed Consent Form: Not applicable.
Introduction
Hepatitis A is an acute infectious liver disease caused by the hepatitis A virus, a nonenveloped, single-stranded RNA picornavirus belonging to the genus Hepatovirus (1,2). Its transmission occurs mainly via the fecal-oral route, through the consumption of contaminated water or food, as well as via direct contact (oro-anal) with infected people (3).
While most cases are self-limiting and resolve spontaneously, especially among children, the infection can progress to severe forms, particularly in adults or individuals with comorbidities (4). In these cases, fulminant hepatitis can occur - characterized by acute liver failure, encephalopathy, and coagulopathy - in addition to systemic complications such as acute renal failure, sepsis, and metabolic disorders, often requiring intensive care and liver transplantation as a rescue measure (2).
In recent decades, a transition in the epidemiological pattern of hepatitis A has been observed in several countries (5). Improved sanitation conditions have reduced early exposure to the virus, increasing susceptibility among adolescents and young adults, age groups in which infection can be more symptomatic and severe (5). In Brazil, this transition is also manifested with localized outbreaks, often affecting specific populations, such as men who have sex with men (6).
Between November 2023 and May 2024, the municipality of Curitiba, Paraná, Brazil, experienced an outbreak of hepatitis A with deaths (7). The viral circulation of hepatitis A in localized outbreaks, such as the one recorded in Curitiba, poses a significant risk to the adult population, which is more susceptible to severe forms of the disease (8). The potential occurrence of unfavorable clinical outcomes, such as fulminant hepatitis, requires early recognition of clinical and epidemiological risk factors to mitigate mortality. The characterization of severe cases is therefore essential to support surveillance, optimize clinical management, and strengthen the public health response.
The study aimed to describe the epidemiological profile of the hepatitis A outbreak in Curitiba, Paraná, between November 2023 and May 2024, with emphasis on the clinical and laboratory characterization of cases that progressed to death or liver transplantation.
Methods
Design
This is a descriptive case series study of hepatitis A, with emphasis on severity outcomes, confirmed in Curitiba, Paraná, Brazil, between November 1, 2023, and May 29, 2024.
Context
Curitiba, Paraná, has a resident population of 1,773,718 inhabitants (9). This study was conducted during a hepatitis A outbreak, with 281 confirmed cases reported from November 1, 2023, to May 29, 2024. The municipal epidemiological surveillance system notifies hepatitis A cases in the Notifiable Diseases Information System (SINAN). It monitors outbreak severity using data from the Mortality Information System (SIM) and coordination with the Hospital Epidemiological Surveillance Centers (NHVE).
This study was conducted by a team from the Training Program in Epidemiology Applied to the Unified Health System Services (EpiSUS-Avançado), in partnership with the local surveillance team, to ensure the findings could be readily applied to the outbreak response. It originated from an urgent epidemiological surveillance action at the invitation of the municipality.
Participants
The study included all individuals residing in Curitiba, Paraná, with a confirmed hepatitis A diagnosis reported in the SINAN during the study period. Individuals without laboratory confirmation by serology were excluded. Severe cases were defined as those that progressed to death or required liver transplantation as a result of infection with the hepatitis A virus.
Variables
In the general description, sociodemographic variables (sex, age, race/skin color, education, and place of residence) were analyzed. In the series of severe cases, clinical information (comorbidities, homelessness status, signs and symptoms, complications, therapeutic interventions, and clinical outcome) and laboratory information (blood count, liver transaminases, alkaline phosphatase, bilirubin, urea, creatinine, sodium, potassium, and International Normalized Ratio) were also included. The designation A to F was used to describe severe cases and maintain anonymity.
Data sources
Epidemiological and demographic data for all confirmed cases were primarily extracted from SINAN (hepatitis A notifications). To identify severity outcomes, constant coordination was made with the NHVE to confirm deaths and liver transplant procedures, and to verify cases reported as deaths due to hepatitis A in SIM. For identified severe cases (death or transplant), a thorough review of electronic and physical medical records was conducted, extracting clinical and laboratory data, and using the day with the highest glutamic-oxaloacetic transaminase value as the reference for laboratory data. To ensure data quality and consistency, key information was collected using a spreadsheet validated by the local surveillance team. The official geographic boundaries of the Curitiba Health Districts were used to represent the distribution of cases, based on their addresses in the SINAN database.
Biases
Potential sources of bias in this study include reporting bias and information bias. Reporting bias may have occurred due to non-diagnosis and, consequently, underreporting of mild or asymptomatic hepatitis A cases in SINAN, limiting the representativeness of the total number of cases in the outbreak. Information bias may have occurred due to the use of secondary and retrospective data (SINAN, SIM, and medical records), considering the potential incompleteness or heterogeneity in the quality of records of sociodemographic, clinical, and laboratory variables.
Study size
The study analyzed all laboratory-confirmed hepatitis A cases reported during the study period (n=281) and all severe cases (n=6). No sample size calculation was performed because this is a descriptive case series study that includes the complete universe of events of interest.
Statistical analyses
Absolute and relative frequencies, measures of central tendency (median), and dispersion (interquartile ranges) were calculated using Microsoft Excel 2016, R in the RStudio interface (v. 4.4.0), and QGIS (version 3.34) for map creation.
Results
During the analyzed period, 281 confirmed cases of hepatitis A were identified, the majority (74.7%) being male (Table 1). The median age of the cases was 30 (interquartile range [IQR] =13).
The health districts of Matriz (23.0%) and Portão (17.0%) accounted for the majority of hepatitis A cases during the period from November 1, 2023, to May 29, 2024 (Figure 1).
Of the confirmed cases of hepatitis A, six (n=6) were classified as severe cases, with five deaths and one liver transplant due to the infection. Of these six cases, five were male. Among these cases, two individuals were homeless at the time of infection. The median age was 43 years (IQR = 13).
The most frequent symptoms were jaundice (5/6), nausea, and abdominal pain (both in 4/6). The main complication observed was acute renal failure (5/6). Two cases met clinical criteria for liver transplantation, and the procedure was performed in one of them. All patients required intensive care unit care. Five received mechanical ventilation via orotracheal intubation and blood product transfusions (Table 2).
The length of hospital stay ranged from 6 to 41 days, with a median of 11 days. All deaths occurred during hospitalization (Table 3).
Liver enzymes, specifically glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase, were more than a hundredfold above the reference limit. Systemic involvement was confirmed by a median International Normalized Ratio three times the reference value and marked hyperbilirubinemia. Laboratory results included acute renal dysfunction (median creatinine of 3 mg/dL [IQR=5]) and hematological abnormalities such as leukocytosis and thrombocytopenia (Table 4).
Discussion
The hepatitis A outbreak in Curitiba showed a predominance among young adult males, with territorial concentration in well-structured central districts, and with cases that progressed to severe forms. Severe cases were characterized by significant hepatic and renal dysfunction, a high frequency of complications, and the need for intensive support, culminating in unfavorable outcomes - transplantation and death. These findings reinforce that, although generally self-limiting, hepatitis A can progress abruptly and severely.
Among the study limitations, the use of secondary data and the restriction to information such as laboratory tests stand out, which prevented the monitoring of the evolution of clinical parameters throughout hospitalization. The possibility of underreporting and the use of secondary data, which are subject to underreporting, incompleteness, and heterogeneity in quality across systems and medical records, should also be considered when interpreting the results.
The median age of severe cases was higher than the median observed in the overall outbreak, suggesting that advanced age may have contributed to a more unfavorable course of infection. The predominance of males among severe cases follows the sociodemographic distribution of the overall outbreak. However, it is more pronounced than the predominance recorded in the national data from 2012-2022, in which cases were distributed between 53.8% men and 46.2% women (10). In 2022, this difference increased, with 64.0% of cases in men, often associated with specific behavioral networks and greater exposure to risky practices (11-12-13). Such evidence highlights the importance of targeted strategies, such as health education actions on the risks of transmission through contaminated food or water and via sexual contact, and expanding vaccination coverage for groups at higher risk in epidemic contexts, in line with the literature (14,15).
The predominance of the white race/skin color reflects the municipality’s demographic composition (16). The concentration of cases in the health districts of the municipality’s northern region, such as Matriz and Portão, located in more developed and central areas of the city, suggests localized transmission in urban contexts with better infrastructure, contrasting with the pattern classically associated with conditions of greater socioeconomic vulnerability and poor sanitation (3,17). This pattern reinforces the hypothesis that behavioral factors and specific contact networks are involved in transmission dynamics.
The proportion of cases that progressed to death is slightly higher than the standard (<1%) described in the literature (2), underlining the vulnerability of the population. The occurrence of fulminant hepatitis, although rare, is recognized as more frequent in adults and in the presence of comorbidities, such as alcoholic liver disease and hepatic steatosis (4). These findings reinforce the potential severity of hepatitis A virus infection in specific clinical and epidemiological contexts and underscore the need for a structured care response that focuses on early detection of severe cases and timely access to specialized care during outbreaks.
The chronological analysis of clinical events highlights the often insidious nature of the progression of hepatitis A to severe forms in adults. The prolonged interval between symptom onset and first medical attention may result from a low perceived severity. The wide variation in the time to hospitalization reflects the heterogeneity of clinical presentation and the need for a high index of suspicion in rapidly progressing cases. The presence of two homeless individuals among the severe cases reinforces the association between social vulnerability and adverse outcomes. This association has been described in urban outbreaks and supports the recommendation to include socially vulnerable populations in immunization strategies (15).
The manifestations observed among the severe cases - jaundice, acute renal failure, encephalopathy, and the need for intensive support - are consistent with the patterns described in severe cases of hepatitis A (2). The significant elevation of transaminases, bilirubin, and international normalized ratio, coupled with renal impairment, suggests progression to hepatorenal syndrome in some cases, a condition associated in the literature with a guarded prognosis (18,19). This laboratory pattern reinforces the need for early recognition and specialized management in a hospital setting.
The hepatitis A outbreak in Curitiba highlighted that, even in areas with consolidated health infrastructure, the infection can progress to severe forms, with high clinical complexity and risk of fatal outcomes. The findings emphasize the importance of sensitive surveillance, early recognition of severity, expansion of vaccination coverage, and coordination among primary care, surveillance, and hospital services as central strategies to reduce morbidity and mortality in epidemic scenarios.
Data availability:
The anonymized databases used in this study are publicly available in the SciELO Datarepository, linked to the journal Epidemiologia e Serviços de Saúde (RESS), and can be accessed at:https://data.scielo.org/dataset.xhtml?persistentId=doi:10.48331/SCIELODATA.CDJTUW. The dataset should be cited according to the reference provided in the repository.
References
- 1 Feinstone SM, Kapikian AZ, Purcell RH. Hepatitis A: detection by immune electron microscopy of a viruslike antigen associated with acute illness. Science. 1973;182(4116):1026-8.
-
2 Lai M., Chopra S. Hepatitis A virus infection in adults: epidemiology, clinical manifestations, and diagnosis [Internet]. UpToDate. 2024 [cited 2025 Nov 17]. Available from: Available from: https://www.uptodate.com/contents/hepatitis-a-virus-infection-in-adults-epidemiology-clinical-manifestations-and-diagnosis
» https://www.uptodate.com/contents/hepatitis-a-virus-infection-in-adults-epidemiology-clinical-manifestations-and-diagnosis -
3 World Health Organization. Hepatitis A: key facts [Internet]. 2023 [cited 2025 Nov 17]. Available from: Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-a
» https://www.who.int/news-room/fact-sheets/detail/hepatitis-a - 4 Hofmeister MG, Xing J, Foster MA, Augustine RJ, Burkholder C, Collins J, et al. Factors associated with hepatitis A mortality during person-to-person outbreaks: a matched case-control study-United States, 2016-2019. Hepatology. 2021;74(1):28-40.
- 5 Jacobsen KH. Globalization and the changing epidemiology of hepatitis A virus. Cold Spring Harb Perspect Med. 2018;8(10):a031716.
- 6 Madalosso G, Kamioka GA, Bassit NP, Pavanello EI, Sousa SCZ, Koizumi IK, et al. Surto de hepatite A em homens que fazem sexo com homens no município de São Paulo, Brasil, 2017. Braz J Infect Dis. 2018;22:5.
-
7 Prefeitura de Curitiba. Surto de hepatite A em Curitiba tem transmissão de pessoa a pessoa: são 255 casos e 5 mortes confirmadas em 2024 [Internet]. 2025 [cited 2025 Nov 17]. Available from: Available from: https://www.curitiba.pr.gov.br/noticias/surto-de-hepatite-a-em-curitiba-tem-transmissao-de-pessoa-a-pessoa-sao-255-casos-e-5-mortes-confirmadas-em-2024/73751
» https://www.curitiba.pr.gov.br/noticias/surto-de-hepatite-a-em-curitiba-tem-transmissao-de-pessoa-a-pessoa-sao-255-casos-e-5-mortes-confirmadas-em-2024/73751 - 8 Shin EC, Jeong SH. Natural history, clinical manifestations, and pathogenesis of hepatitis A. Cold Spring Harb Perspect Med. 2018;8(9):a031708.
-
9 Instituto Brasileiro de Geografia e Estatística. Censo 2022 [Internet]. 2022 [cited 2025 Nov 17]. Available from: Available from: https://www.ibge.gov.br/estatisticas/sociais/trabalho/22827-censo-demografico-2022.html
» https://www.ibge.gov.br/estatisticas/sociais/trabalho/22827-censo-demografico-2022.html -
10 Ministério da Saúde (BR). Boletim epidemiológico: hepatites virais 2023 [Internet]. 2023 [cited 2025 Nov 17]. Available from: Available from: https://www.gov.br/aids/pt-br/central-de-conteudo/boletins-epidemiologicos/2023/hepatites-virais/boletim-epidemiologico-hepatites-virais-_-2023.pdf/view
» https://www.gov.br/aids/pt-br/central-de-conteudo/boletins-epidemiologicos/2023/hepatites-virais/boletim-epidemiologico-hepatites-virais-_-2023.pdf/view - 11 Nicolay N, Le Bourhis-Zaimi M, Lesourd A, Martel M, Roque-Afonso AM, Erouart S, et al. Description of a hepatitis A outbreak in men who have sex with men, Seine-Maritime, France, 2017. BMC Public Health. 2020;20(1):1441.
- 12 Ndumbi P, Freidl GS, Williams CJ, Mårdh O, Varela C, Avellón A, et al. Hepatitis A outbreak disproportionately affecting men who have sex with men in the European Union and European Economic Area, 2016-2017. Euro Surveill. 2018;23(33):1700641.
- 13 Rosendal E, von Schreeb S, Gomes A, Lino S, Grau-Pujol B, Magalhães S, et al. Ongoing outbreak of hepatitis A associated with sexual transmission among men who have sex with men, Portugal, 2023-2024. Euro Surveill. 2024;29(21):2400272.
- 14 Castro LS, Rezende GR, Pires Fernandes FR, 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.
- 15 Hennessey KA, Bangsberg DR, Weinbaum C, Hahn JA. Hepatitis A seroprevalence and risk factors among homeless adults in San Francisco. Public Health Rep. 2009;124(6):813-7.
-
16 Instituto Brasileiro de Geografia e Estatística. Censo demográfico 2022: panorama [Internet]. 2024 [cited 2025 Nov 17]. Available from: Available from: https://censo2022.ibge.gov.br/panorama/
» https://censo2022.ibge.gov.br/panorama/ - 17 Carrilho FJ, Mendes Clemente C, Silva LC. Epidemiology of hepatitis A and E virus infection in Brazil. Gastroenterol Hepatol. 2005;28(3):118-25.
- 18 Choi HK, Song YG, Han SH, Ku NS, Jeong SJ, Baek JH, et al. Clinical features and outcomes of acute kidney injury among patients with acute hepatitis A. J Clin Virol. 2011;52(3):192-7.
- 19 Andrievskaya M, Lenhart A, Uduman J. Emerging threat: changing epidemiology of hepatitis A and acute kidney injury. Adv Chronic Kidney Dis. 2019;26(3):171-8.
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Use of generative artificial intelligence:
The initial version of the introduction was prepared with the support of an artificial intelligence tool (ChatGPT, GPT-4.0) to structure the section. The discussion was revised using the same tool to improve clarity. All references included in the manuscript were selected by the authors and checked in their full versions, ensuring the veracity and originality of the information presented.
Edited by
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Editor-in-Chief:
Jorge Otávio Maia Barreto https://orcid.org/0000-0002-7648-0472
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Scientific Editor:
Maria Auxiliadora Parreiras Martins https://orcid.org/0000-0002-5211-411X
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Associate Editor:
Mariana Del Grossi Moura https://orcid.org/0000-0003-4268-4298
