Metabolomic Signatures Predictive of Fulminant Hepatic Failure In Autoimmune Hepatitis: A Cross-Sectional Study

Abstract

Background: Autoimmune hepatitis may rarely present with fulminant hepatic failure, but routine liver tests may not fully characterize the metabolic disruption associated with this severe phenotype. Serum metabolomics may identify pathway-level disturbances related to energy metabolism, bile acid handling, amino acid imbalance, and mitochondrial stress. Objective: To compare serum metabolomic profiles between autoimmune hepatitis patients with and without fulminant hepatic failure and identify candidate metabolites associated with the fulminant phenotype. Methods: This cross-sectional study included 86 autoimmune hepatitis patients from tertiary care hospitals in Punjab, Pakistan. Thirty-two patients had fulminant hepatic failure and 54 did not. Clinical features, liver function tests, coagulation profile, immunoglobulin G, autoantibodies, and serum metabolomic profiles were assessed. Serum samples were analyzed using liquid chromatography–mass spectrometry. Group differences, fold changes, receiver operating characteristic curves, and adjusted associations were evaluated. Results: Patients with fulminant hepatic failure had higher bilirubin, ALT, AST, INR, and lower albumin. Lactate, pyruvate, phenylalanine, tyrosine, glutamine, total bile acids, and medium-chain acylcarnitines were higher in the fulminant group, while branched-chain amino acids were lower. Lactate showed the highest reported AUC, followed by total bile acids and phenylalanine. Conclusion: Fulminant hepatic failure in autoimmune hepatitis was associated with a distinct metabolomic pattern reflecting energy failure, bile acid overload, amino acid imbalance, and mitochondrial stress. These exploratory findings require validation in larger longitudinal studies