Drug induced liver injury in patients on anti-tubercular therapy and/or anti-retroviral therapy at Helen Joseph hospital, Johannesburg, South Africa

Abstract

Background South Africa has one of the highest prevalence rates of human immunodeficiency virus (HIV) and tuberculosis (TB) globally, and an estimated 73% of patients with TB are co-infected with HIV. The anti-tubercular drugs and anti-retroviral drugs are known to cause drug induced liver injury (DILI). In addition, these patients may be on other hepatotoxic medication and acquire other opportunistic infections which can also cause liver injury. The consequences are treatment failure, disease relapse and drug resistance. Objectives To study patients on anti-tubercular and/or anti-retroviral therapy with DILI to establish their demographics, clinical presentation and severity, time to presentation from initiation of drug therapy, management and outcomes. Methods A retrospective review of patients who presented with DILI to Helen Joseph hospital over a 17-month period from October 2015 to February 2017 was done. The records of 129 patients were analysed and data collected on drug history, biochemical investigations and any relevant imaging studies available. Results: Of the 129 patients, 61% were male (n=79) and 39% female (n=50). Forty-six patients had anti-tubercular DILI (36% of patients), 29 had anti-retroviral DILI (22% patients) and 54 patients (42%) were on both anti-tubercular and anti-retroviral therapy. The median age of patients was 35.4 years (IQR 31.4-43.5 years). Twenty percent of the patients were on a concomitant hepatotoxic drug, cotrimoxazole (p <0.05). None of the patients were co-infected with Hepatitis C and 4.7% patients had co-infection with Hepatitis B. The commonest presenting symptom was nausea and vomiting followed by jaundice. Of the patients with anti-retroviral DILI, 89% were on first line treatment with tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV), with a median CD4 count of 549 cells/microlitre and median viral load of 549 copies/ml. The median time to development of DILI was 85 days from initiation of anti-retroviral therapy. Of the patients with anti-tubercular DILI, 76% were on a regimen with rifampicin/isoniazid/pyrazinamide/ethambutol (RIF/INH/PZA/ETH), with a median CD4 count of 37.5 cells/microlitre and median viral load of 57,400 copies/ml. The median time to development of DILI from initiation of anti-tubercular therapy was 14 days. In the patients with mixed DILI, 89% were on first line anti-retroviral therapy (TDF/FTC/EFV) and 70.4% on RIF/INH/PZA/ETH containing anti-tubercular therapy. Their median CD4 count was 56 cells/microlitre and median viral load 1230 copies/ml. In this group anti-retroviral therapy was used for a median 168 days prior to presentation and anti-tubercular therapy for a median of 41 days. Overall the in-hospital mortality of these patients was 16.3% (n=21). Conclusion Patients with anti-tubercular DILI presented earlier (within intensive phase of therapy) whereas those anti-retroviral DILI presented up to 1 year after therapy initiation; this highlights the importance of maintaining a high index of suspicion in this group of patients and regular surveillance for earlier diagnosis of DILI to reduce associated morbidity. Those with anti-retroviral DILI presented with lower viral loads and higher CD4 counts likely reflecting adequate HIV therapy. Only 27% of those with anti-retroviral DILI and 35% of those with anti-tubercular DILI were successfully re-challenged to their original drug regimen by discharge. Among those admitted with DILI, those with severe DILI and mixed pattern of liver injury were at increased risk of all-cause mortality during the admission.