Diagnostic Utility of Liver Biopsy in Persistent Unexplained Liver Enzyme Elevation: A Retrospective Cohort Study

Abstract

Background and Aims: Chronically elevated liver enzymes without a clear etiology remain a frequent diagnostic challenge. This study evaluated the diagnostic yield of liver biopsy in such cases and assessed if laboratory parameters predict histological clarification. Methods: We retrospectively analyzed 71 patients with unexplained elevated liver enzymes who underwent percutaneous liver biopsy between 2015 and 2021 at a tertiary referral center in Germany. Clinical characteristics and lab values were compared between patients with clarified and unclarified diagnoses. ROC analysis was performed for ALT and AST. Histopathological characteristics and biopsy-related complications were recorded. Results: A definitive diagnosis was reached in 47.9% of cases. The most frequent findings were autoimmune hepatitis (35.3%), drug-induced liver injury (23.5%), and NAFLD (23.5%). ALT and AST levels were significantly higher in patients with clarified diagnoses (ALT: p = 0.0079; AST: p = 0.0096). ROC analysis showed moderate performance (ALT AUC = 0.684; AST AUC = 0.679). Fibrosis stages ≥ F2 were found in 28.2% of patients. Biopsy complications occurred in 2.8%, all minor. Conclusions: Liver biopsy clarified the etiology in nearly half of patients and revealed diagnoses not apparent through non-invasive work-up. While ALT and AST levels were associated with diagnostic yield, they lacked sufficient predictive value. Biopsy remains a valuable tool in selected patients with unexplained liver enzyme elevations.