Clinicopathological Profile and Outcomes of Severe Hepatitis A Outbreak in India: A Multicenter Cross-sectional Study

A resurgence of hepatitis A virus (HAV) outbreak unfolded in the state of Kerala despite high sanitation and socioeconomic standards. Clinicians observed a possible new emerging phenotype marked by atypical features like persistent fever after the appearance of clinical jaundice, early renal and pulmonary involvement, and hemophagocytic lymphohistiocytosis (HLH).

We conducted a multicenter, hospital-based study across six tertiary care centers, prospectively enrolling patients with serologically confirmed HAV (anti-HAV IgM positive) presenting with acute liver injury. Patients with ≥2 atypical manifestations (persistent fever, acute kidney injury [AKI], HLH, or pulmonary involvement) comprised the a-HAV arm, while outpatients with usual symptoms (u-HAV) served as the comparator.

A total of 324 patients (a-HAV: 179, u-HAV: 145) were included (mean age: 32 ± 12.8, 68.2% males). The a-HAV arm had a significantly higher incidence of hepatomegaly (64% vs 44%), splenomegaly (30% vs 17%), ascites (30% vs 9%), encephalopathy (21%), prolonged cholestasis (19%), higher mean levels of total leukocyte count (TLC), bilirubin, aspartate aminotransferase, international normalized ratio (INR), triglycerides, ferritin, and lactate dehydrogenase. Atypical features included continuing fever (93%), pulmonary complications (16.8%), AKI (13.4%), and HLH (12.8%). a-HAV required aggressive therapeutic interventions with higher steroid use (30% vs 4.1%), plasma exchange (21%; mean: 2.68 ± 1.26 cycles, 2240 ± 634.45 mL exchanged), continuous renal replacement therapy (7.8%), and mechanical ventilation (10%). Also, progression to acute-on-chronic liver failure (7.3%), autoantibodies (18%), metabolic acidosis (6.7%), readmissions (9%), and mortality (11.7%) were higher in the a-HAV arm. On multivariable analysis, the model incorporating baseline ammonia (odds ratio [OR]: 1.11), TLC (OR: 2.21), and INR (OR: 7.20) demonstrated the highest discriminative performance for 90-day mortality (area under the receiver operating characteristic curve: 0.994). Genotyping revealed the strain to be of genotype IIIA.

The study provides a strong indication regarding the changing clinical presentation and virulence of HAV. Unlike previous outbreaks, a significant number of patients had severe presentations marked by immune dysregulation and multiorgan involvement. Early recognition and tailored management are the keys to improving patient outcomes.