Browsing by Author "Sonderup, Mark"
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- ItemOpen AccessA Decade of Hepatitis C at the UCT/GSH Liver Clinic in the Pre-DAA era(2019) Nordien, Rozeena; Sonderup, Mark; Spearman, WendyBackground Hepatitis C (HCV) in South Africa is incompletely characterised and understood. Epidemiological and clinical data will better inform our understanding and assist national policy decision making. On the background of more than two decades of clinical challenges in HCV management, the advent of direct acting antivirals (DAA) now makes HCV elimination plausible. To better understand the base from which we come, we elected to review and characterise our HCV experience at Groote Schuur Hospital (GSH) in the Pegylated interferon (Peg-IFN) and Ribavirin (RBV) management era. Methods Patients with chronic HCV attending GSH Liver Clinic from 2002 to 2014, were included, in the analysis. Relevant data were extracted from a registry and existing clinical records accessed. Two brands of Peg-IFN were available and those treated with the first generation add-on protease inhibitor, telaprevir, were included. Results 238 patients were included in the analysis, median age of 47 (IQR 37-58) years, men 60.5%. Men were significantly younger than women, 43.5 (35-52) vs 55 (42-64) years, respectively, p< 0.0001. Ethnically, the majority were white (55.9%) or mixed-ancestry (21.8%), 16.4% were HIV co-infected, 3.7% hepatitis B (HBV) co-infected and 0.4% triple infected with HCV, HBV and HIV. The most likely mode of HCV acquisition was blood/blood product exposure prior to 1992 (32.8%) and injecting drug use (IDU) 17.6%, while 30.3%, had no clear risk factor identifiable. Genotypes (GT) 1 to 5 were observed with GT-1 (34.9%) predominating. In those biopsied, (n=90), 30% ≥F3 fibrosis, with 15.6% cirrhotic. With IL28B polymorphisms, heterozygous CT (23.9%) and CC genotype (15.5%), were most frequent. 32.6% accessed Peg-IFN/Ribavirin-based therapy, 6.5% (n=5) with add-on telaprevir. GT-1 (35.1%) was most prevalent in the treatment group, followed by GT-3 (26%) and GT-5 (18.2%); 10% were HIV co-infected. Overall SVR rate was 75.3% with 37% of GT-1 not achieving SVR; 49.4% experienced adverse events including cytopaenias (32.5%) and depression (15.6%) with 15.6% requiring erythropoietin for anaemia and 15.6% GM-CSF for neutropaenia. Conclusion HCV patients in the Peg-IFN/Ribavirin management era typified the epidemiology of HCV. GT distribution was pangenotypic and treatment outcomes were encouraging despite treatment challenges. Patient selection, IL28B and sensible cytopaenia support, likely accounted for this. However numbers treated were limited and the DAA era of therapy allows for a rapid expansion of therapy with now growing numbers of patients and a changing local epidemiology.
- ItemOpen AccessThe natural history of Efavirenz Drug Induced liver injury(2020) Maughan, Deborah; Spearman, Catherine Wendy; Sonderup, MarkBackground 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.