Histopathological Predictors of Drug-Induced Liver Injury in Hospitalized Adults Receiving Long-Term Pharmacotherapy

Abstract

Background: Drug-induced liver injury (DILI) presents significant diagnostic and prognostic challenges among patients receiving long-term pharmacotherapy. Histopathological assessment may provide valuable insights into hepatic injury severity and subsequent biochemical recovery.

Objective: To evaluate the association between hepatic histopathological features and persistent biochemical abnormalities at six months among hospitalized adults with DILI.

Material and Methods: This multicenter retrospective observational study included 150 hospitalized adults evaluated for suspected DILI during prolonged pharmacotherapy at participating institutions in Sialkot, Lahore, and Quetta, Pakistan, from January 2022 to February 2023. Histopathological parameters included hepatocellular necrosis, interlobular bile duct paucity, portal and lobular inflammation, cholestasis, ductular reaction, and fibrosis. Associations with six-month biochemical outcomes were assessed using univariable statistical analyses.

Results: Of 150 patients, 72 (48.0%) were men and 78 (52.0%) were women. At six months, 111 patients (74.0%) achieved biochemical recovery, while 39 (26.0%) exhibited persistent abnormalities. Portal inflammation (67.3%) and lobular inflammation (66.0%) were the most frequently observed histopathological findings. Interlobular bile duct paucity was significantly associated with biochemical persistence (odds ratio [OR] 5.04; 95% confidence interval [CI] 1.92–13.19; p=0.001), as was confluent hepatocellular necrosis (OR 4.06; 95% CI 1.89–8.74; p<0.001).

Conclusion: Interlobular bile duct paucity and confluent hepatocellular necrosis demonstrated significant unadjusted associations with persistent biochemical abnormalities at six months. These histopathological features may contribute to identifying patients at increased risk of delayed biochemical recovery following DILI.

Keywords: Drug-induced liver injury; Histopathology; Bile duct paucity; Hepatocellular necrosis; Biochemical recovery; Long-term pharmacotherapy.