The natural history of Efavirenz Drug Induced liver injury

Maughan, Deborah

The natural history of Efavirenz Drug Induced liver injury

Master Thesis

2020

Abstract

Background Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), has been a component of first line antiretroviral treatment in the South African HIV/AIDS programme since 2004. Similarly, it is extensively used in ART programmes in other low and middle incomes countries. The natural history of the previously reported EFV drug induced liver injury (DILI), is unknown. Objectives To establish causality assessment for the drug-induced liver injury and elucidate the natural history of EFV DILI by observing a cohort of patients through documenting all the factors influencing the patterns of clinical and histological injury, the time to clinical and biochemical recovery, the associated mortality rate and to establish if any demographic or clinical factors predict poor outcomes. Methods Patients were prospectively included after establishing causality criteria for EFV DILI. Clinical, demographic and histological features were carefully documented from the time of presentation and through follow up. Prednisone at 0.25-0.5mg/kg was initiated at the discretion of the treating hepatologist. Risk factors for severe injury or death and time to event (full clinical recovery and full biochemical recovery) were analyzed. Results 50 patients were included in the analysis, median age 34 (IQR 29-39) years, men significantly older than women, p=0.014. Most (92%) were female gender, and of black African ethnicity (86%). The median duration on ART at time of presentation was 6.5 months with half of the women initiating ART during pregnancy at a median gestation of 24 weeks (IQR 11 – 36). Median CD4 nadir at ART treatment initiation was 517 cells/mm3, with no significant difference (p=NS) in CD4 nadir in those pregnant or not. Median RUCAM score was 7 and of the 66% of patients who had liver biopsies, 3 histological patterns were identified: submassive necrosis (57,5%), nonspecific hepatitis (36%) and mixed cholestatic hepatitis (6%). Multivariate analysis suggested predictors for the development of submassive necrosis included age >30 years [OR 0.86 (0.15-0.97), p=0.02], pregnancy [OR 6.9 (1.34 – 35.6), p=0.02]; CD4 >350 [OR, 7.1 (1.5-31.9), p=0.02] but not alcohol use [OR 1.17 (0.72-1.18); p=0.07]. For the non-specific hepatitis group, only pregnancy predicted [OR 8.7 (1.3- 58.2), p=0.03]. The mortality rate was 14%, median time from admission to death was 15 days with the median duration to initial hospital discharge 33 (IQR 24 -52) days. Biochemical recovery was prolonged necessitating a follow up period of more than a year at an outpatient specialist clinic. 86% initiated protease inhibitor based ART successfully. Conclusion EFV DILI is a severe injury with significant inpatient mortality and morbidity requiring prolonged hospitalization and outpatient follow up.

Keywords

Medicine

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