Serum Hepatocyte Growth Factor Predicts Outcomes in Non‐Acetaminophen Drug‐Induced Acute Liver Failure

BACKGROUND AND AIMS: Regenerative capacity and inflammatory responses are key determinants of outcome in acute liver failure (ALF). However, their prognostic significance in non-acetaminophen drug-induced liver injury with acute liver injury or ALF (non-APAP-DILI-ALI/ALF) remains poorly defined. We aimed to identify biomarkers of regeneration and inflammation associated with clinical outcomes in this population. METHODS: We evaluated clinical laboratory parameters and circulating biomarkers in 79 patients with non-APAP-DILI-ALI/ALF (20 with ALI, 59 with ALF) and 19 healthy donors. We used multivariable logistic regression to identify independent predictors of 21-day transplant-free survival among these patients. These predictors were used to create a composite model that was compared with the Model for End-Stage Liver Disease (MELD) score. RESULTS: Markers reflecting hepatic synthetic dysfunction (TBIL, INR, MELD) were strongly associated with the outcomes, whereas aminotransferases were not. HGF levels were markedly elevated in non-APAP-DILI-ALI/ALF patients versus healthy donors (5070 ± 4001 vs. 276 ± 581 pg/mL; p < 0.001), increased with injury severity, and were highest in patients who died or underwent transplantation (6421 ± 4359 vs. 4102 ± 3456 pg/mL; p = 0.009). Among inflammatory mediators, only interleukin-6 showed a modest association with outcome. We developed an H-Score based on the three variables independently associated with survival on multivariable analysis: HGF (odds ratio, 1.0002; p = 0.048), TBIL and INR. The H-Score outperformed MELD overall (area under the curve, 0.819 vs. 0.713) and in ALF only patients (0.811 vs. 0.643; p = 0.040). CONCLUSIONS: HGF provides independent prognostic value beyond standard measures in non-APAP-DILI-ALF. The H-Score may improve risk stratification over the MELD score and warrants validation in a prospective cohort.