A Clinical-Pathological Analysis of Drug-Induced Hepatic Injury After Liver Transplantation

ObjectiveThe objective of this study was to investigate the histopathologic characteristics and clinical features of drug-induced hepatic injury after liver transplantation.MethodsWe retrospectively analyzed histopathologic characteristics and clinical features of 160 liver biopsy specimens obtained from 131 posttransplantation patients who were diagnosed as having drug-induced hepatic injury from June 2000 to August 2006 in our center.ResultsThe histopathologic features of drug-induced hepatic injury after liver transplantation were characterized as centrilobular hepatocyte edema, fatty change, and variable intrahepatic cholestasis. Adverse drug reactions were diagnosed between days 5 and 1643 after transplantation, including 44.38% (71/160) at 5–30 days, 17.50% (28/160) at 31–90 days, and 38.12 (61/160) at 90–1643 days. The incidence of hepatic injury due to antifungal drugs, antibiotics, antiviral drugs, or other agents was 29.38% (47/160), 22.50% (36/160), 16.25% (26/160), and 31.87% (51/160), respectively. Abnormalities in routine liver function tests included ALT elevation >300 μ/L in 87 patients (54.38%), ALP elevation >300 μ/L in 37 patients (23.13%) or total bilirubin elevation >60 μmol/L in 36 patients (22.50%). Drug-induced toxic liver injury is characterized by a single notable increase in ALT, ALP, or TB, especially ALT. Common clinical manifestations were flu, rash, gastrointestinal symptoms, and eosinophilia.ConclusionDrug-induced hepatic injury commonly appears within 30 days or after 90 days posttransplantation. Injury emerging within 30 days is always caused by antifungal, antiviral, or antibiotic drugs, whereas it displays more complicated reasons after 90 days. Drug-induced hepatic injury shows a complex and variable clinical manifestation. According to pathologic findings of liver biopsy, adequate drug history, and relationship between drug administration and onset of clinical manifestations, clinicians and pathologists can make a definitive diagnosis and access the extent of injury.