Predictors of intravenous amiodarone induced liver injury

Abstract

Background: Intravenous (IV) amiodarone may be associated with liver injury that may necessitate drug discontinuation. The prediction of amiodarone induced liver injury (AILI) and its severity may help careful patient monitoring or the choice of other measures alternative to amiodarone in high risk patients. Little is known regarding predictors of AILI.

Objectives: To address the predictors of AILI and its severity.

Methods: The study included 180 patients indicated for IV amiodarone therapy who were divided into 2 groups: cases (90 patients) who developed AILI, and controls (90 patients) who did not develop AILI. AILI was defined as aminotransferase (ALT and AST) elevation by ⩾2 folds of baseline levels. Severe AILI was defined as enzyme elevation by >5 folds of baseline values.

Results: Multivariate analysis showed that the presence of cardiomyopathy (P = 0.032), congestive hepatomegaly (P = 0.001), increasing baseline total bilirubin (P < 0.0001), direct current cardioversion (P = 0.015), and increasing dose of amiodarone (P = 0.014) to be independent predictors for AILI. Regarding severity of AILI, inotropic support (P = 0.034), congestive hepatomegaly (P = 0.012), increasing baseline total bilirubin (P = 0.001), and increasing dose of amiodarone (P = 0.002) were found to be independent predictors for severe AILI. Among cases, linear regression analysis showed that baseline ALT was the only significant independent predictor of post-amiodarone ALT (P < 0.0001), while baseline AST (P < 0.0001) and EF (P = 0.012) were the only significant independent predictors of post-amiodarone AST.

Conclusions: Compromised cardiac, hepatic, and hemodynamic conditions, with increasing dose of IV amiodarone were associated with AILI. Severity of liver injury had linear relationship with baseline aminotransferase levels and left ventricular systolic function.

Keywords: AILI, amiodarone induced liver injury; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CM, cardiomyopathy; DILI, drug induced liver injury; Drug induced liver injury; Intravenous amiodarone; Liver injury; Parenteral amiodarone; ULN, upper limit of normal.

Figure 1

A: ROC curve showing predictive effect of total bilirubin on amiodarone induced liver injury (AUC 0.72, 95% CI: 0.64–0.79, P < 0.0001). A value of >1.3 mg/dl was the best cutoff value that is likely associated with amiodarone induced liver injury. B: ROC curve showing predictive effect of total bilirubin on severe (grade 4) amiodarone induced liver injury (AUC: 0.67, 95% CI: 0.6–0.74, P < 0.0001). A value of >1.6 mg/dl was the best cutoff value that is likely associated with severe amiodarone induced liver injury.

Figure 2

Correlations with post-amiodarone aminotransferases, showing significant correlations with each of baseline ALT (A), AST (B), total bilirubin (C), and ejection fraction (D).

Figure 3

Illustrative summery of our findings, showing predictors of the occurrence and severity of IV amiodarone induced liver injury in the present study. Solid arrows indicate multivariate predictors. Dashed arrows indicate univariate predictors. ALT: Alanine aminotransferase. EF: Ejection fraction.