P- 61 DRUG-INDUCED LIVER INJURY: REPORTING CHALLENGES AND ENZYMATIC CHANGES IN PATIENTS USING ANTIBIOTICS – RETROSPECTIVE STUDY

Introduction and Objectives

Drug-induced liver injury (DILI) - an underreported adverse event (AE) - is classified as hepatocellular, cholestatic or mixed, through the alanine-aminotransferase (ALT) and alkaline phosphatase ratio, when ALT > 2x the upper limit of normal (LSN). Polypharmacy and conditions can change these data. In hospitalized patients, antibiotics (ATB) are one of the most prescribed drugs, can cause DILI. We aimed to evaluate the profile and frequency of ALT in patients using ATB amoxicillin-clavulanate (AMX_CLAV), cefepime (CEF) and meropenem (MPN), verifying possibility and type of DILI, notifications in the Hospital Pharmacovigilance System (SFH) and what limitations lead to underreporting.

Materials and Methods

partial retrospective analysis of medical records of patients admitted to University Hospital, with ALT>2xLSN, using the referred ATB; AEs collection from the hospital and Anvisa databases, assessing causes of underreporting. Statistical significance was 5% and analyzes were performed using SPSS® program.

Results

In 2018, 739 hospitalized patients had ALT>2xLSN. Of these, 45% used ATB [AMX_CLAV (2.3%); CEF (27.2%); MPN (15.6)]. Death in patients with ALT>2xLSN was 40.1%, majority CID A41.9 (27.3%). K72.0 [Chronic Liver Failure] scored 3.5%. 24.9%(n=184) had ALT>5xULN and of these, death in 53.3%(n=98)(p<0.001). Use of CEF and MPN was significantly higher in deaths compared to non-deaths (39.9% x 18.7%, p<0.001/27.7% x 7.4%, p<0.001, respectively CEF and NMP). Concurrently, SFH investigated 139 notifications, 6.5% ATB AEs (n=9). Of the cases, 4 reported hepatotoxicity, ALT being reported for MPN and AMX_CLAV. In ALT>5xLSN patients, there were 3 cholestatic (3.8%), 18 mixed (60.0%) and 3 hepatocellular (13%)(p<0.001).

Conclusions

Hepatocellular injury in hospitalized patients with ALT>5xULN using ATB is more severe, although the mixed pattern is more frequent. There is no active pharmacovigilance in DILI considering ALT; spontaneous reports are underreported due to the complexity of the DILI diagnosis, lack of specific tests and data in the medical records.