Evolving trends in hepatitis A epidemiology: Shifting patterns, emerging risks, and future strategies

Table 1 Clinical course and manifestations of hepatitis A virus infection

Phase	Approximate duration	Key clinical manifestations	Laboratory/virological findings
Incubation	2-6 weeks (mean 28 days)	Asymptomatic	HAV replication in liver; high virus in stool and blood; normal ALT
Prodromal (pre-icteric)	3-10 days	Fatigue, anorexia, nausea, low-grade fever, right upper quadrant discomfort, diarrhea in children	Rapid ALT/AST rise (> 1000 IU/L); HAV in stool; start of IgM anti-HAV appearance
Icteric phase	1-3 weeks	Jaundice, dark urine, pale stools, pruritus; fever and malaise subside	Peak ALT/AST; elevated bilirubin; IgM anti-HAV positive
Convalescent/recovery	Several weeks-months	Gradual improvement; residual fatigue	Enzyme levels normalize; IgM declines; IgG persists lifelong

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HAV: Hepatitis A virus; Ig: Immunoglobulin.

Table 2 Endemicity levels based on the age-specific seroprevalence of hepatitis A virus in the general population

Endemicity level	Age-specific seroprevalence
High	90% by 10 years of age
Intermediate	50% by 15 years, with < 90% by 10 years
Low	50% by 30 years
Very low	< 50% by 30 years

Table 3 Global variation in hepatitis A vaccine provision and access

Vaccine policy	Cost coverage	Equity/operational notes	Ref.
Routine childhood vaccination; targeted adult vaccination (VFC program)	Free under VFC; OOP for adults without insurance	Outbreaks in PEH and drug-using adults; gaps in adult uptake	Nelson et al[41], United States
Targeted (indigenous, travelers, PEH)	Provincial programs; partial coverage	Uneven uptake across provinces	Palaisy[42], Canada
Universal childhood vaccination (≥ 12 months)	Government-funded	High coverage; regional disparities in remote areas	Brito and Souto[43], Brazil
Integrated in national schedule (since 2023)	Free public sector	Rapid rollout post-urban outbreaks	Guzman-Holst et al[44], Mexico
Universal single-dose schedule	Government-funded	Successful herd immunity; sustained low incidence	Flichman et al[45], Argentina
Targeted (travelers, men who have sex with men, PEH)	National Health Service covers high-risk groups	Limited adult awareness	Johnson et al[46], United Kingdom
Recommended (travelers, men who have sex with men, laboratory staff)	Reimbursed by insurance	Stable low incidence; high cost limits universal rollout	Szucs[47], Germany
Universal since 2003 in several regions	Government-funded	Decline in hepatitis A virus cases; regional autonomy causes inconsistency	Bechini et al[48], Italy
Targeted vaccination	Regional funding	Good outbreak response; inequity across regions	Urbiztondo et al[49], Spain
Included in routine childhood schedule in 2008	Government-funded	High coverage; rare outbreaks	Ryani[50], Saudi Arabia
Universal childhood (since 2011)	Fully subsidized	Excellent coverage nationwide	Yigit and Kalayci[51], Turkey
Targeted vaccination (private market)	Mostly OOP	High-cost limits uptake; growing private sector use	Shah et al[52], India
Targeted; not yet universal	OOP except high-risk groups	Declining seroprevalence; debate on adding to National Immunisation Programme	Poovorawan et al[53], Thailand
Universal childhood vaccination since 2008	Government-funded	Dramatic incidence decline; urban-rural gap remains	Yan et al[54], China
Targeted (travelers, men who have sex with men)	OOP	Low uptake; periodic import-linked outbreaks	Kanda et al[12], Japan
Targeted (travelers, laboratory staff)	OOP	Low uptake due to cost; increasing adult outbreaks	Patterson et al[55], South Africa
Not routine; private market only	OOP	High endemicity; vaccine not prioritized	Ahmed and Nashwan[56], Pakistan

OOP: Out of pocket; PEH: People experiencing homelessness; VFC: Vaccines for Children.

Table 4 Age-stratified seroprevalence and age at midpoint of population immunity estimates reflecting hepatitis A virus endemicity transitions

Country	Overall seroprevalence	Age at midpoint of population immunity (years)	Endemicity level	Key findings	Ref.
Iran	86%	21	High to intermediate	Declining natural immunity in younger cohorts due to improved sanitation	Lankarani et al[63]
Jordan	38.3%	21-30	Intermediate to low	Introduction of HAV vaccine resulted in epidemiological shift of HAV seroprevelance	Kareem et al[64]
Turkey	67.23% over all; 35.9% in 15-18 years	Estimated 25-30	Intermediate	Low seroprevelance in youth is due to the fact that these individuals were not included in routine vaccination	Karabey et al[65]
Vietnam	69.2% (total), 57.9% (urban), 80.7% (rural)	29	High to intermediate	Socio-economic disparities and unsafe drinking water contribute to geographic difference	Cam Huong et al[66]

HAV: Hepatitis A virus.

Table 5 Outbreaks related to hepatitis A virus infection

Group	Region	Key details	Ref.
Men who have sex with men	Europe, United States, Israel, Chile, Poland, Barcelona	1400 cases in 16 European Union/European Economic Area countries; three HAV strains; linked outbreaks in Israel/Chile; mostly non-immune men who have sex with men engaging in high-risk sexual behaviour, increase risk with concomitant HIV infection	Ndumbi et al[89], Enkirch et al[90], Raczyńska et al[91], Dabrowska et al[92]
Patient who inject drugs	California, Michigan, Kentucky, Utah, London, Ontario	Increased HAV cases among persons who inject drugs or homelessness due to low vaccination coverage, syndemic involving concomitant HIV, HCV, HAV and group A streptococcal infection	Foster et al[93], Turner[94]
Foodborne	Europe, Italy, Sweden, Austria, United States, Michigan	Large European Union and Italy outbreak from frozen berries; Sweden, Austria, Michigan linked to imported strawberries; outbreaks from contaminated food or infected food handlers	Fallucca et al[95], Authority[96], Hutin et al[97], Greig and Ravel[98]
Travelers/migration	France, United States of America (United States)	Travel-related cases account for approximately 30%-46% of HAV cases in United States/Europe; 254 cases of hepatitis A in international travellers, with most cases occurring in unvaccinated individuals	Migueres et al[99], Balogun et al[100]
Homelessness	San Diego (United States), San Francisco (United States)	People experiencing homelessness had 3.3 × higher odds of infection, higher hospitalization and death rates; prevalence increased with years of homelessness, injection drug use, and foreign-born status	Peak et al[101], Hennessey et al[102]
Community transmission	Brazil, Germany	Person-to-person transmission common in enclosed spaces; 34.3% of household contacts infected; outbreak among Ukrainian war refugees and volunteer caregiver	Lima et al[103], Krumbholz et al[104]
HIV positive patients	Iran, Warsaw, Poland	97.7% HAV seroprevelance; outbreaks in HIV positive men who have sex with men	Dabrowska et al[92], Omidifar et al[105]
Chronic liver disease (HBV and HCV)	Italy, Argentenia	HAV superinfection causes severe disease, fulminant hepatitis; higher fatality in coinfected patients; HAV outbreaks among men who have sex with men show high rates of HIV, syphilis and HBV co-infection	Vento et al[106], Marciano et al[107]
Metabolic dysfunction associated steatotic liver disease	United States	Increase odds of liver fibrosis	Vassilopoulos et al[108]

HAV: Hepatitis A virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus.