DOI: 10.1001/jamainternmed.2026.3831 ISSN: 2168-6106

Serologic Immunity to Hepatitis A and B in US Adults and High-Risk Populations

Giovanni A. Roldan, Jesse Fletcher, Timothy Davie, Thomas M. Leventhal, John R. Lake, Prowpanga Udompap

Importance

Serologic immunity to hepatitis A virus (HAV) and hepatitis B virus (HBV) protects against acute infection and severe outcomes among high-risk groups; however, contemporary data on population-level immunity remain limited, especially in high-risk populations.

Objective

To estimate the prevalence and factors associated with serologic immunity in the overall population and across high-risk subgroups, including those with chronic liver disease (CLD), chronic kidney disease, diabetes, and immunosuppression and pregnant people.

Design, Setting, and Participants

This cross-sectional study used data from the National Health and Nutrition Examination Survey from January 2017 to August 2023 and included adults aged 20 years or older with available HAV and HBV serologic test results. Data were analyzed from January 3 to May 10, 2026.

Main Outcomes and Measures

The primary outcomes were the prevalence of serologic immunity to HAV, defined by hepatitis A antibody positivity, and HBV, defined by hepatitis B surface antibody positivity, with vaccine-derived immunity specifically identified by surface antibody positivity in the absence of hepatitis B core antibodies. Data were weighted to generate nationally representative estimates of the US adult population. Multivariable survey-weighted logistic regression models were used to identify independent factors associated with viral hepatitis immunity.

Results

Among 13 514 individuals, representing an estimated 226.1 million US adults (mean [SE] age, 48.65 [0.40] years; 51.76% female), 39.5% (95% CI, 37.7%-41.3%) demonstrated serologic immunity to hepatitis A, corresponding to approximately 89.4 million individuals. For HBV, 27.1% (95% CI, 25.8%-28.4%) demonstrated serologic immunity, corresponding to approximately 61.3 million individuals, while vaccine-derived immunity was present in 25.2% (95% CI, 23.9%-26.5%). In adjusted models, HAV immunity was associated with younger age (eg, 20-29 vs ≥65 years: adjusted odds ratio [AOR], 0.51; 95% CI, 0.44-0.60); lower educational attainment (eg, <grade 9 vs college graduate or above: AOR, 0.32; 95% CI, 0.24-0.42); non-Hispanic Black (AOR, 1.67; 95% CI, 1.34-2.09), Mexican American (AOR, 4.22; 95% CI, 3.42-5.21), other Hispanic (AOR, 2.01; 95% CI, 1.60-2.54), non-Hispanic Asian (AOR, 3.03; 95% CI, 2.45-3.76), and multiracial or other (AOR, 1.36; 95% CI, 1.04-1.79) race and ethnicity; being born outside the US (AOR, 4.54; 95% CI, 3.74-5.52); and liver disease awareness (OR, 1.65; 95% CI, 1.29-2.09). Obesity was associated with lower odds of HAV immunity (AOR, 0.83; 95% CI, 0.72-0.96). Vaccine-derived HBV immunity was associated with younger age (eg, 20-29 vs ≥65 years: AOR, 0.18; 95% CI, 0.15-0.23), female sex (AOR, 1.36; 95% CI, 1.18-1.56), non-Hispanic Asian (AOR, 1.47; 95% CI, 1.17-1.86) and non-Hispanic Black (AOR, 1.15; 95% CI, 1.00-1.32) race and ethnicity, and higher educational attainment (eg, <grade 9 vs college graduate or above: AOR, 3.29; 95% CI, 2.35-4.61). In high-risk subgroups, HAV immunity ranged from 26.7% (95% CI, 18.9%-34.4%) for metabolic dysfunction–associated alcohol-related liver disease to 63.7% (95% CI, 50.0%-77.4%) for chronic HBV infection, while HBV vaccine-derived immunity ranged from 14.0% (95% CI, 11.3%-16.6%) for chronic kidney disease to 38.6% (95% CI, 28.0%-49.1%) for pregnancy.

Conclusions and Relevance

This cross-sectional study found that population-level serologic immunity to HAV and HBV was suboptimal and substantial susceptibility persisted across high-risk clinical subgroups. These findings highlight persistent gaps in viral hepatitis protection and support targeted, systematic vaccination strategies for HAV and HBV, especially among high-risk populations.

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