Clinical characteristics of drug-induced liver injury and related risk factors

Abstract

Drug-induced liver injury (DILI) is often undiagnosed or misdiagnosed clinically because of diagnostic difficulties caused by lack of laboratory-specific serological markers. In this study, we comprehensively assessed the clinical characteristics, laboratory indices, hepatotoxic drugs, risk factors and outcomes concerning DILI, and explored the similarities in mechanisms between Chinese and Western drug-induced DILI. Patients with a first diagnosis of DILI and a Roussel Uclaf Causality Assessment Method (RUCAM) score >3 points were enrolled for systematic retrospective study. Their clinical characteristics, clinical classification, risk factors, laboratory indices, hepatotoxic drugs and outcomes were analyzed. Cholestatic patients had the highest alkaline phosphatase (ALP) and prothrombin time activity (PTA) levels (P<0.05). Patients with medication time ≥30 days had significantly higher positive rate of autoantibodies than those with medication time <30 days. Odds ratio values for DILI-related factors such as hepatobiliary diseases, immune dysfunction, diabetes, hypertension, chronic alcohol consumption and age ≥45 years were 6.552, 6.130, 3.774, 2.801, 2.002 and 1.838, respectively. Pathogeneses of Chinese and Western drug-induced DILI may be substantially the same. DILI accompanied with autoantibody positivity may indicate severe liver injury outcome. Hepatobiliary diseases, diabetes and hypertension are likely to increase drug susceptibility, and more prone to cause liver injury.

Drug induced liver injury with analysis of alternative causes as confounding variables

“…As early as in 1993 and for the first time (Table ) with RUCAM, a valid search for diagnoses as alternatives to DILI was feasible , confirmed in the RUCAM updated in 2016 . Progress in search for alternative causes was made in other studies published in 1999 and in subsequent years in reports using RUCAM (Table ) .…”

“…The principal goal was to assess the frequency and the type of published alternative causes in the 21 articles of the global case series (Table ) . All reports published a variable number of cases with suspected DILI that were not DILI.…”

“…Listing of the 21 reports with published alternative causes in initially suspected DILI cases . Causality assessment methods refer to RUCAM (Roussel Uclaf Causality Assessment Method) ; the MV scale of Maria and Victorino; and the method of DILIN (Drug‐Induced Liver Injury Network).…”

“…However, the articles addressing the issue of alternative causes are still limited despite abundant publications on DILI in the scientific literature. Problems of the 21 publications with variables confounding the DILI diagnosis obviously became evident during case assessment or re‐evaluation prior to submission to the journal, recognized and published by the authors of the original reports .…”

“…Among the 21 publications reporting alternative causes in DILI series , 18 reports used RUCAM (Table ) . The preference for RUCAM is in line with its use for evaluations by regulators, registries, case series, and case reports .…”