Factors associated with hepatitis A mortality during person-to-person outbreaks: A matched case-control study-United States, 2016-2019.

BACKGROUND & AIMS During 2016-2020, the United States experienced person-to-person hepatitis A outbreaks that are unprecedented in the vaccine era, during which case-fatality ratios reported by some jurisdictions exceeded those historically associated with hepatitis A. APPROACH & RESULTS To identify factors associated with hepatitis A-related mortality, we performed a matched case-control study (matched on age [±5 years] and county of residence in a 1:4 ratio) using data collected from health department and hospital medical records of outbreak-associated patients in Kentucky, Michigan, and West Virginia. Controls were hepatitis A outbreak-associated patients who did not die. There were 110 cases (mean age 53.6 years) and 414 matched controls (mean age 51.9 years); most cases (68.2%) and controls (63.8%) were male. Significantly (p 2 (aOR 10.3), and platelet count <150,000/uL (aOR 3.7) among hepatitis A outbreak-associated patients in the independent multivariable conditional logistic regression analyses (each model adjusted for sex). CONCLUSIONS Pre-existing liver disease, diabetes, cardiovascular disease, and initial MELD score ≥30, AST/ALT ratio ≥1, or platelet count <150,000/uL among hepatitis A patients were independently associated with higher odds of mortality. Providers should be vigilant for such features and have a low threshold to escalate care and consider consultation for liver transplantation. Our findings support the Advisory Committee on Immunization Practices recommendation to vaccinate persons with chronic liver disease, though future recommendations to include adults with diabetes and cardiovascular disease should be considered.