Serum Hepatocyte Growth Factor Predicts Outcomes in Non‐Acetaminophen Drug‐Induced Acute Liver Failure
Tao Wang, Silvia M. Bacot, Kamai Patterson, Devira Friedman, Caroline Taylor, Huixiao Hong, Jie Liu, Mark I. Avigan, Paul Hayashi, Jody A. Rule, William M. Lee, Jorge Rakela, Gerald M. Feldman, Minjun ChenABSTRACT
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.