OP-1 FEATURES OF IDIOSYNCRATIC DRUG-INDUCED LIVER INJURY (DILI) IN LATIN AMERICA: LONG-TERM EXPERIENCE OF THE LATINDILI NETWORK

Introduction and Objectives

The Latin American DILI (LATINDILI) Network is an international registry of prospectively identified drug-induced liver injury (DILI) cases to enhance case characterization. We aimed to analyze features and outcomes of DILI in Latin America.

Materials and Methods

Information of DILI cases included in the LATINDILI database between 2011 and July 2022 was collected and analyzed.

Results

Of 468 patients included, 13 had positive rechallenge and 5 recurrent DILI (different drugs). Mean age was 49 years (range 14- 89), 62% women. The most common type of injury was hepatocellular (62%). Overall, 42% of patients were hospitalized. Most cases were mild/moderate, but 6.2% were considered severe, and 4.1% resulted in death/liver transplantation. Overall, eleven cases (2.4%) developed chronic DILI (no biochemical resolution within one year), and nine had drug-induced autoimmune-like hepatitis (1.9%).

Histological information was available for 80 patients (17%), of whom 5 had chronic cholestasis with ductopenia. The most frequent drugs were amoxicillin-clavulanate (12%), herbal and dietary supplements (HDS, 9%), anabolic androgenic steroids (4.9%), anti- tuberculosis medications (anti-TB) and nitrofurantoin (4.3% each). Among the 15 most common causative agents, all but azathioprine, were associated with cases fulfilling nR-based Hy's law. However, only anti-TB, nimesulide and HDS were associated with worst outcome cases, while many were not, such as amoxicillin-clavulanate, nitrofurantoin and diclofenac. Causative agents more common in women included methyldopa (100%) nitrofurantoin (95%) and nimesulide (86%), while cyproterone (100%) and phenytoin (67%) were more common in men.

Conclusions

The increasing number of liver injuries associated with HDS is a major concern in Latin America. The predictive value of the nR-based Hy's law is drug-specific. These findings have regulatory implications for the promotion of public health, as common DILI- causing drugs in Latin America are either second-line drugs, no longer in use, or have been withdrawn from other markets due to liver toxicity. Funding: AEMPS, CIBERehd,ISCIII-FEDER (PI21/01248,PI-0310-2018).