Determinants, profile and outcomes of hepatitis A virus–associated severe acute liver injury in adults

Hepatitis A virus (HAV)-related hepatitis is witnessing an epidemiological transition with increasing trends in adults. While uncomplicated hepatitis remains common, evidence suggests it to be a growing cause for acute liver failure (ALF). In between the two extremes exists severe acute liver injury (s-ALI) which has a propensity to transition to ALF. We aimed at describing the clinical profile of patients with HAV-related s-ALI and identifying potential predictors of progression to ALF.

This was a single-center retrospective analysis of adult patients admitted with HAV-related s-ALI between April 2022 and December 2023. Demographic and laboratory parameters were compared between patients with only s-ALI and those with ALF. Predictors of progression from s-ALI to ALF were identified using logistic regression.

Forty-three patients satisfied criteria of s-ALI, of which 33 (76.7%) had only s-ALI, while 10 (23.3%) had ALF. Patients with s-ALI had lesser leukocytosis (6.3 ± 3 vs. 13.2 ± 4.8), less incidence of acute kidney injury (9.1% vs. 40%) and lower model for end-stage liver disease (MELD) (20 [18–24.5] vs. 31.5 [26–42]), arterial lactate (2.1 [1.3–3.1] vs. 6.3 [5.2–8.0]), arterial ammonia (94 [72–118] vs. 299 [188–573]), procalcitonin (0.5 [0.28–1.25] vs. 3.2 [1.2–6.1]) and ferritin (482 [213–1633] vs. 5186 [1341–11,053]) compared to HAV-ALF (p < 0.05 for all). Three patients (9.09%) with s-ALI progressed to ALF of whom one (3%) died. Baseline ammonia levels (unadjusted odds ratio [OR] 1.03 [1.01–1.06]) and leukocyte count (OR 1.00 [1.00–1.01]) tended to be associated with ALF progression, although none was significant after multi-variable adjustment. Ammonia levels had an area under receiver operating curve of 0.816 (0.64–0.93) (p = 0.009) (cut-off of 144 μmol/L). Additional comorbidities did not impact overall outcomes.

HAV presents as s-ALI in young adults, with almost one in 10 progressing to ALF. Baseline ammonia may be an important predictor of progression even in s-ALI, but mandates larger well-designed studies.