Biomarkers Significance 5/10

Serum HGF improves prognostic stratification over MELD in non-acetaminophen acute liver failure

The study evaluated circulating biomarkers in 79 patients with non-acetaminophen drug-induced acute liver injury or failure to identify predictors of 21-day transplant-free survival. Serum hepatocyte growth factor (HGF) was significantly elevated in patients compared with healthy controls and correlated with disease severity and mortality or transplantation. Investigators combined HGF with total bilirubin and INR to develop an H-Score that outperformed the standard MELD score in predicting survival (AUC 0.819 versus 0.713 overall, and 0.811 versus 0.643 in acute liver failure patients). The findings suggest that incorporating HGF into risk stratification models could enhance prognostic accuracy for liver failure, though prospective validation is required before clinical implementation.

The original study

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

Authors
Wang T, Bacot SM, Patterson K, Friedman D, Taylor C, Hong H, et al.
Journal
Liver international : official journal of the International Association for the Study of the Liver
Type
Journal Article
PMID
42817738
Read the original study →

Original abstract

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.