A clinical-pathological analysis of drug-induced hepatic injury after liver transplantation.
OBJECTIVE
The objective of this study was to investigate the histopathologic characteristics and clinical features of drug-induced hepatic injury after liver transplantation.


METHODS
We 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.


RESULTS
The 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 micro/L in 87 patients (54.38%), ALP elevation>300 micro/L in 37 patients (23.13%) or total bilirubin elevation>60 micromol/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.


CONCLUSIONS
Drug-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.
Zhenglu
W
W
Transplantation Department, Tianjin First Central Hospital, Tianjin, PR China. wangzhenglu186@sina.com
Hui
L
L
Shuying
Zh
Zh
Wenjuan
C
C
Zhongyang
Sh
Sh
D002779:Cholestasis / Q000139:chemically induced / Q000473:pathology; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000293:injuries*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects / Q000473:pathology*; D011183:Postoperative Complications / Q000139:chemically induced / Q000473:pathology*; D011184:Postoperative Period; D012189:Retrospective Studies; D013997:Time Factors; D014947:Wounds and Injuries / Q000139:chemically induced*