Drug and herb-induced liver injury: A critical review of Brazilian cases with proposals for the improvement of causality assessment using RUCAM

Abstract

Introduction and objectives: Although hepatotoxicity accounts for 10% of adverse drug reactions, it remains poorly understood and underreported. This study aimed to summarize case reports of herb- and drug-induced liver injury in Brazil.

Methodology: Systematic review in the following databases: PubMed, SciELO, Science Direct, CAPES, and gray literature.

Results: Twenty-seven studies reporting 32 cases were identified. Brazilian cases were primarily detected in hospitals, and occurred mainly in young males suffering from chronic diseases. Drugs (n=29) were a more frequent cause of liver injury than herbs (n=3). Almost a third of these drugs were anticonvulsants, and 15 appear in the Brazilian List of Essential Medicines. In 50% of the cases, clinical manifestations started within 30 days of drug ingestion. Regarding the decline of liver enzymes, 50% of the cases reached normality after drug withdrawal. However, 7 deaths and 2 liver transplantations were reported. Only one study assessed causality using RUCAM.

Conclusion: Given the severe outcomes of DILI and HILI, early detection and management of hepatotoxicity to increase drug safety are necessary, as well as pharmacotherapeutic monitoring of patients with chronic diseases. Moreover, the application of the RUCAM algorithm in clinical practice has to be further disseminated.

Keywords: Adverse effects; Chemical and drug-induced liver injury; Pharmaceutical services; Pharmacovigilance.