Analysis of occurrence and influencing factors of liver injury related to amphotericin B

Abstract

Objective To explore the occurrence of hepatic injury related to amphotericin B and analyze its influencing factors. Methods The medical records of inpatients, who received amphoteric B during hospitalization and had complete records of liver function before and after medication, were searched from the Hospital Information System of Zhongshan Hospital, Fudan University from January 2013 to December 2017 and analyzed retrospectively. Liver injury was classified and diagnosed according to the Guidelines for the diagnosis and treatment of drug-induced liver injury and its incidence was calculated. According to the age (≤45 or >45 years old), with or without history of liver injury/liver disease within 3 months before admission, the dosage form of amphotericin B (non-liposome or liposome), the maximum daily dose ( 21 d), the cumulative dose (<600 or ≥600 mg), cumulative dose/body mass (<10 or ≥10 mg/kg), with or without combination use of liver-protective drugs, and with or without combination use of other drugs with hepatotoxicity, the patients were divided into 2 groups, respectively. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), alkaline phosphatase (ALP), and gamma-glutamyltransferase (γ-GT) were compared respectively in patients in each 2 groups with above-mentioned 11 different clinical features. The influencing factors of hepatic injury related to amphotericin B were analyzed using multivariate logistic regression analysis and multiple linear regression analysis, whose effect values were expressed as odds ratio (OR) with 95% confidence interval (CI) and standardized regression coefficient with 95%CI and value of R2. Results A total of 42 patients were enrolled, including 31 males and 11 females with ages from 13 to 92 years old and body mass (65.0±12.3)kg. Of the 42 patients, 26 patients were ≥45 years old; 15 patients had history of hepatic injury/liver disease; 30 patients used amphotericin B, 10 used amphotericin B liposome, and 2 used both of them; 25 patients received the maximum daily dose of amphotericin B <30 mg and the maximum daily dose/body mass <0.5 mg/kg, 17 patients had the maximum daily dose ≥30 mg and the maximum daily dose/body mass ≥0.5 mg/kg; 28 patients used amphptericin B with step-up dosage, 14 patients′ initial doses were the maximum daily dose; 24 patients′ cumulative dose of amphotericin B and the cumulative dose/body mass were <600 mg and <10 mg/kg, respectively, while 18 patients′ cumulative dose of amphotericin B and the cumulative dose/body mass were ≥600 mg and 10 mg/kg, respectively; 29 patients received combination use of hepato-protective drugs; 33 patients received combination use of other hepatotoxic drugs. The levels of TBil and ALT in 42 patients after amphotericin B treatment were obviously higher than those before medication (P=0.019, P=0.017). Seven patients were diagnosed as drug-induced liver injury, the incidence of drug-induced liver injury was 16.7%. The result of multivariate logistic regression analysis showed that history of hepatic injury/liver disease within 3 months before admission was the independent risk factor for elevated γ-GT level after medication (OR=2.029, 95%CI: 1.037-3.970, P=0.039). The results of multiple linear regression analysis showed that the maximum daily dose ≥30 mg and the cumulative dose ≥600 mg were the independent risk factors for elevated TBil level after medication (standardized regression coefficient: 0.59, 95%CI: 0.28-0.90, P=0.001; standardized regression coefficient: 1.61, 95%CI: 0.14-3.07, P=0.033; R2=0.524); hepatic injury/liver disease within 3 months before admission was the independent risk factor for elevated ALP and γ-GT levels after medication (standardized regression coefficient: 0.85, 95%CI: 0.25-1.45, P=0.006, R2=0.205; standardized regression coefficient: 0.89, 95%CI: 0.29-1.50, P=0.005, R2=0.206). Conclusions The incidence of liver injury related to amphotericin B in Zhongshan Hospital, Fudan University is 16.7%. The maximum daily dose of amphotericin B ≥30 mg and cumulative dose ≥600 mg are the independent risk factors for the elevated level of TBil, history of hepatic injury/liver disease within 3 months before admission is the independent risk factors for elevated levels of ALP and γ-GT. Key words: Amphotericin B; Chemical and drug induced liver injury; Risk factors