Drug-induced liver injury causality assessment data from a crosssectional study in Brazil: a call for the use of updated RUCAM in hospital Pharmacy

Abstract

Objective: to identify the frequency of DILI inpatients from abnormal liver enzyme levels using the updated Roussel Uclaf Causality Assessment Method (RUCAM) causality assessment algorithm, as well as to provide a descriptive analysis of DILI cases. Methods: we conducted a crosssectional study in a medium complexity hospital in southern Brazil. Data regarding DILI was collected retrospectively from electronic medical records (EMR) in 2015. Inclusion criteria were all adult patients (≥ 18 years old) who presented alanine aminotransferase (ALT) greater than twice the superior limit of normality (ALT > 60 UI/L) with concomitant change of aspartate aminotransferase (AST) or alkaline phosphatase (ALP) or change of ALP greater than twice the superior limit of normality (ALP > 250 UI/L) during hospitalization. The RUCAM was applied to all suspected DILI cases. Results: 84,134 inpatients in this period; 178 patients had abnormal liver tests, six patients had sufficient medical information to allow DILI causality assessment, and two patients had DILI described in EMR, although our group could not find suficient information to apply RUCAM retrospectively. Absence of information was mainly related to drug reconciliation at hospital admission, time of onset of suspected drug therapy and no description of previous clinical conditions in EMR. Four patients developed hepatic injury as a result of drug treatment initiated during hospitalization. Suspected drugs were antibiotics, nonsteroidal anti-inflammatory drugs, antiviral, tuberculostatics and platelet antiaggregant. Liver injury pattern was identified as hepatocellular and mixed. Conclusion: DILI appeared as a rare ADR, but absence of data in most EMR affected the application of RUCAM and underestimated DILI frequency. There is an urgency to develop DILI knowledge in Brazilian hospitals. Pharmacists must be aware of the use of the updated RUCAM to prospectively assess possible DILI cases. For future research, we suggest to combine cross-linking DILI tracers such as ICD-10 liver injury codes, abnormal liver biomarkers, search for trigger hepatotoxicity drugs and EMR text search tools, adding artificial intelligence to pharmacovigilance and hospital pharmacy.