A Comprehensive Molecular and Serological Investigation of Hepatitis A Virus Among Patients With Suspected Acute Hepatitis: A Brazilian Study

Abstract

Hepatitis A Virus (HAV) infects millions of individuals annually and is a major cause of acute viral hepatitis worldwide. This study aims to (1) assess HAV infection in suspected acute hepatitis patients at public healthcare institutions in Brazil; (2) evaluate the proportion of immunized individuals against HAV; (3) identify HAV genotypes; (4) examine the association between HAV infection and demographic data, as well as exposure to risk factors. This is a prospective, observational multicenter study conducted in primary health services in Brazil from October 2019 to May 2023, involving 1721 patients with suspected acute hepatitis. Acute HAV infection was identified in 108 (6.3%) patients, predominantly in young men (80%) and from South and Southeast regions of Brazil (97%). Anti-HAV IgG, indicating previous exposure or vaccination, was detected in 78.6% of individuals (74% in the South to 91% in the North). Genotype I.A was found in all cases and approximately 450 mutations were identified, most of them in the structural proteins VP1-3. Two viral groups were identified and related to two introductions of the virus: cosmopolitan sequences from North America, South America, and Europe, and a minor group of Brazilian sequences similar to Asian and South American ones. The high incidence of acute HAV infections highlights the need for targeted prevention and vaccination strategies. The characterization of HAV genetic diversity and molecular epidemiology contributes to monitoring and identifying emerging outbreaks.

Keywords: Brazil; HAV; epidemiology; immunization program; serology; viral hepatitis.

Figure 1

IgG anti‐HAV seroprevalence by age group.

Figure 2

Acute hepatitis A (AHA) [anti‐HAV IgM or HAV RNA (+)] prevalence by age group.

Figure 3

Whole genome alignment of the HAV sequence from São José dos Campos collected in September 2022 against reference strain EU131373. The alignment reveals a 1‐nucleotide deletion within the VP2 protein‐coding region. A detailed view of the alignment highlights the specific location of the deletion, which may have implications for protein function, viral fitness or immunogenicity.

Figure 4

Rooted phylogenetic trees based on complete genomes of the hepatitis A virus reconstructed using maximum likelihood. Names in red are the samples with reference genotype. (A) Phylogenetic tree with all genotypes of HAV; (B) Phylogenetic tree only with genotype IA genomes plus IB external groups. Branches with bootstrap support above 70% are marked with green (A) or purple (B) circles next to the corresponding branch.