Thieves of the state and the South African Medical Association (SAMA)

No Abstract

A decade of hepatitis C at the University of Cape Town/Groote Schuur Hospital Liver Clinic, South Africa, in the pre-direct-acting antivirals era

Background. Hepatitis C virus (HCV) in South Africa (SA) is incompletely characterised and understood. Epidemiological and clinical data will better inform our understanding and assist national policy decision-making. Against the background of more than two decades of clinical challenges in HCV management, the advent of direct-acting antivirals (DAAs) now makes HCV elimination plausible.Objectives. To better understand the base from which we come, we elected to review and characterise our HCV experience at Groote Schuur Hospital (GSH), Cape Town, SA, in the pegylated interferon (Peg-IFN) and ribavirin (RBV) management era.Methods. Patients with chronic HCV infection attending the GSH Liver Clinic from 2002 to 2014 were included in the analysis. Relevant data were extracted from a registry and existing clinical records were accessed. Two brands of Peg-IFN were available, and patients treated with the first-generation add-on protease inhibitor telaprevir were included.Results. A total of 238 patients were included in the analysis (median (interquartile range) 47 (37 - 58) years, 60.5% males). Males were significantly younger than females (43.5 (35 - 52) years v. 55 (42 - 64) years, respectively) (p<0.0001). The majority were white (55.9%) or of mixed ancestry (21.8%), 16.4% were HIV co-infected, 3.7% were hepatitis B virus (HBV) co-infected, and 1 patient (0.4%) was triple-infected with HCV, HBV and HIV. The most likely mode of HCV acquisition was blood or blood product exposure prior to 1992 (32.8%) and injecting drug use (17.6%), while 30.3% of patients had no clear risk factor identifiable. Genotypes (GTs) 1 - 5 were observed, with GT-1 (34.9%) predominating. Of patients who were biopsied (n=90), 30.0% had ≥F3 fibrosis, with 15.6% cirrhotic. With IL28B polymorphisms, the heterozygous CT (23.9%) and CC (15.5%) genotypes were most frequent. Of the patients, 32.6% accessed Peg-IFN/RBV-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 (26.0%) and GT-5 (18.2%); 10.0% were HIV co-infected. The overall sustained virological response (SVR) rate was 75.3%, with 37.0% of GT-1 patients not achieving SVR. Of the patients treated, 49.4% experienced adverse events, including cytopenias (32.5%) and depression (15.6%), and 23.4% required cell support in the form of erythropoietin and/or granulocyte-macrophage colony-stimulating factor.Conclusions. HCV patients in the Peg-IFN/RBV management era typified the epidemiology of HCV. GT distribution was pangenotypic, and treatment outcomes were encouraging despite treatment challenges. Patient selection, IL28B and sensible support of cytopenias probably accounted for these favourable outcomes. However, numbers treated were limited, and the DAA era of therapy allows for rapid expansion of therapy with now growing numbers of patients and a changing local epidemiology.

A natural history of efavirenz drug-induced liver injury

Background. Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, has been a component of first-line antiretroviral therapy (ART) in the South African HIV/AIDS programme since 2004. It is extensively used in ART programmes in other low- and middle-income countries. The natural history of the previously recognised EFV drug-induced liver injury (DILI) is not known.Objectives. To define and establish a causality assessment for EFV DILI and document its natural history by detailing a patient cohort. All relevant features characterising the patterns of clinical and histological injury, the duration of clinical and biochemical recovery and the associated mortality rate were documented. Factors associated with specific histological patterns of liver injury were analysed.Methods. Patients were prospectively included after meeting causality and inclusion criteria for EFV DILI. Clinical, demographic and liver histological features (where possible) were documented from the time of presentation and throughout follow-up. Prednisone at 0.25 - 0.5 mg/kg was initiated at the discretion of the treating hepatologist.Results. Fifty patients were prospectively included in the analysis. The median age was 34 (interquartile range (IQR) 29 - 39) years, males being older than females (p=0.014). Most (92%) were female, and 86% were of black African ethnicity. The median duration of ART at presentation was 6 months, with half of the women having initiated ART during pregnancy, at a median gestation of 24 (IQR 11 - 36) weeks. The median CD4 nadir at ART treatment initiation was 517 cells/µL, with no significant difference in CD4 nadir between those who were pregnant and those who were not (p=0.6). The median RUCAM (Roussel Uclaf Causality Assessment Method) score was 7, and among the 75% of patients who had liver biopsies, three histological patterns were identified: submassive necrosis (60%), nonspecific hepatitis (35%), and mixed cholestatic hepatitis (5%). On multivariate analysis, predictors for the development of submassive necrosis included younger age (<30 years; p=0.045), ART initiation in pregnancy (p=0.02), and a baseline CD4 count >350 cells/µL (p=0.018). For the nonspecific hepatitis group, pregnancy was also an associated factor (p=0.04). The mortality rate was 14%, with a median time from admission to death of 15 days. The median (IQR) time to initial hospital discharge was a lengthy 33 (24 - 52) days. Biochemical recovery was prolonged, necessitating a follow-up period of more than a year at an outpatient specialist clinic, with 86% of patients initiating a protease inhibitor-based ART regimen successfully.Conclusions. EFV DILI is a severe drug complication of ART with appreciable mortality and significant inpatient morbidity, requiring prolonged hospitalisation and follow-up

Expanding the epidemiological understanding of hepatitis C in South Africa: Perspectives from a patient cohort in a rural town

Background. The epidemiology of hepatitis C virus (HCV) in the general population of South Africa (SA) is incompletely understood. A high HCV prevalence in key populations is known, but data are limited in terms of a broader understanding of transmission risks in our general population.Objectives. To investigate a patient cohort with HCV infection clustering in a rural SA town, in order to identify possible HCV transmission risks, virological characteristics, phylogenetic data and treatment outcomes.Methods. A cluster of patients with positive HCV serology, previously identified from laboratory records, were contacted by a local district hospital and offered confirmatory testing for HCV viraemia where needed. Those with confirmed HCV RNA were invited to a local hospital visit, where relevant demographic information was recorded, clinical assessment performed and a confidential questionnaire administered. HCV population-based sequencing was performed on HCV NS3/4A, NS5A and NS5B using polymerase chain reaction-specific or M13 universal primers, and sequences were aligned using BioEdit 7.2.5. Phylogenetic trees were constructed. Clinical assessments included liver fibrosis determination with FibroScan (cut-off ≥12.5 kPa = F4). Patients were offered treatment, and sustained virological response (SVR) was confirmed by undetectable HCV RNA at least 12 weeks after the end of treatment.Results. Twenty-one patients, all from the same town, median (interquartile range (IQR)) age 64 (59 - 70) years, 57% female, were evaluated. Of these, 24% (n=5) were HIV co-infected, stable on antiretrovirals. The median (IQR) alanine aminotransferase level was 51 (31 - 89) U/L, with fibrosis distribution including 29% F1, 29% F2, 9% F3 and 33% F4 METAVIR fibrosis. Virologically, two genotypes were observed: 62% (n=13) genotype (GT) 1b and 38% (n=8) GT5a. No patient had ever used injecting drugs, 14% (n=3) had received blood products before 1992, and 9.5% (n=2) had undergone traditional healer-administered scarification. All (n=21) reported attendance at a single primary care clinic in the past, with most (n=20) recalling having received parenteral therapies at the clinic. Phylogenetic analysis of the HCV NS5A and NS5B regions confirmed GT1b and GT5a genotypes and formed two separate clusters within their respective genotypes, suggesting a common source for each genotype infection. Most patients received treatment with sofosbuvir/daclatasvir, 1 was treated with sofosbuvir/velpatasvir, and 1 was re-treated with sofosbuvir/velpatasvir/voxilaprevir. Per protocol SVR was 95%, with the non-SVR patient successfully re-treated.Conclusions. Data from a rural town cluster of patients suggest parenteral medical exposure as the probable common source of hepatitis C transmission risk. The cohort was of older age with a significant number having advanced fibrosis or cirrhosis, suggesting HCV acquisition in the distant past. Using a simplified care approach, treatment outcomes were very good

Tenofovir alafenamide: An initial experience at Groote Schuur Hospital, Cape Town, South Africa

Background. Hepatitis B virus (HBV) remains endemic in South Africa (SA), with a concomitantly high prevalence of HIV co-infection. Chronic kidney disease in these subpopulations also has a high prevalence. Tenofovir is an important component of management, but the associated risk of nephrotoxicity makes dosing a challenge in patients with impaired kidney function. A new formulation, tenofovir alafenamide fumarate (TAF), with a more favourable renal toxicity profile, is now available.Objectives. To evaluate our initial experience of TAF use at Groote Schuur Hospital, Cape Town.Methods. We retrospectively reviewed patients with HBV mono-infection and HIV-HBV co-infection who were initiated on TAF since 2018. We recorded all relevant demographic, serological, virological and biochemical data from patient records. Adherence was documented by pill collection at the pharmacy.Results. A total of 26 patients were included in the evaluation, median (interquartile range (IQR)) age 48 (39 - 51) years, 73% (n=19) male, 27% (n=7) hepatitis B e-antigen-positive, and 46% (n=12) HIV co-infected. The median (IQR) duration of treatment with TAF was 13 (9 - 15) months. The median (IQR) baseline creatinine level was 180 (130 - 227) µmol/L, with significant improvement at 12 months, 122 (94 - 143) µmol/L; p=0.017. Reflecting this change, the estimated glomerular filtration rate improved significantly from baseline to month 12 (42 (25 - 52) and 51 (48 - 68) mL/min/1.73 m2, respectively; p=0.023). Similarly, serum alanine aminotransferase (ALT) normalised from a baseline of 33 (18 - 52) to 18 (15 - 24) U/L at month 12 (p=0.012). HBV DNA viral load also declined, from a baseline of log10 4.04 (2.5 - 7.8) IU/mL to a median of <log10 1.3 IU/mL at month 12. HIV viral load was less than the lower level of quantification at months 6 and 12.Conclusions. TAF was well tolerated, with stable and significantly improving kidney function throughout a 12-month follow-up period. Serum ALT normalised, mirrored by declining HBV viral load. HIV viral load remained undetectable at 6 and 12 months

Hepatitis C prevalence in HIV-infected heterosexual men and men who have sex with men

Background. Globally 1% of individuals are infected with hepatitis C virus (HCV). In South Africa (SA) the prevalence ranges between 0.3% and 1%, with few prospective screening data available. Similarly, local data on transmission modes of HCV are limited, but probably include parenteral routes and pre-1992 blood or blood products. The risk of heterosexual transmission of HCV is low but is increased in men who have sex with men (MSM), with co-transmission risk of both HIV and HCV.Objectives. Given few local data, we sought to better understand HCV characteristics and prevalence in two groups of HIV-infected men.Methods. HIV-positive men in the greater Cape Town metropolitan area were recruited. Sexual orientation was self-identified and demographic and other personal data were obtained via a confidential questionnaire. Participants were screened for HCV after a blood draw. Those with positive HCV tests had further HCV RNA confirmation. Risk factors associated with HCV seropositivity were determined.Results. Five hundred HIV-positive men were recruited, 285 (57.0%) MSM and 215 (43.0%) non-MSM, median age 36 years (interquartile range (IQR) 20 - 64) and 37 years (IQR 21 - 56), respectively (p=NS). Overall, 3.4% (n=17) screened HCV-positive, 5.6% MSM (n=16) and 0.5% non-MSM (n=1); 82.4% were viraemic for HCV RNA. In respect of genotype distribution, 50.0% were infected with genotype 1a, 14.3% with genotype 4 and 35.7% with genotype 2. In terms of risk, MSM were more likely to have used drugs (54.4% v. 30.2%; p<0.001) and to have used all five modes of drug administration (13.0% MSM v. 0.5% non-MSM for injected drugs, 36.1% v. 2.3% for inhaled, 10.0% v. 0% for rectal, 48.1% v. 28.8% for smoked and 27.4% v. 2.3% for oral). More MSM than non-MSM (46.3% v. 16.7%) reported having sex while using recreational drugs, and similarly more MSM (21.4% v. 14%) reported having sex with a sex worker (SW). Risk factors for HCV seropositivity included drug use history (odds ratio (OR) 6.28, 95% confidence interval (CI) 1.78 - 22.12; p=0.004) and in MSM, sex with an SW (OR 5.5, 95% CI 2.06 - 14.68; p=0.001) or use of recreational drugs with sex (OR 6.88, 95% CI 2.21 - 21.44; p=0.001).Conclusions. HCV prevalence in HIV-positive MSM is higher than previously appreciated or documented in SA. Risk factors include injection drug use, use of recreational drugs with sex, and sex with SWs. Targeted interventions are required to address this emerging challenge to achieve the viral hepatitis elimination ideal by 2030.

Acute intermittent porphyria presenting as progressive muscular atrophy in a young black man

Acute intermittent porphyria, the most common porphyria affecting the nervous system, typically presents with neurovisceral crises followed by a motor neuropathy. We describe a 23-year-old black South African man presenting with a progressive stuttering, lower motor neuron syndrome developing over months. He had not experienced pain or neuropsychiatric symptoms. One year after symptom onset he was bed-bound with a flaccid quadriparesis. There was marked amyotrophy, but without fasciculations. Sensation was intact apart from a hypo-aesthetic patch over the thigh. Electrophysiological investigations showed an active motor axonopathy. Urinary porphyrins, δ-aminolaevulinic acid and porphobilinogen were elevated. Mutation analysis revealed the c445C>T (R149X) mutation in the porphobilinogen deaminase gene. The patient responded dramatically to haem arginate and could walk with assistance 2 weeks later. We identified the first molecularly confirmed acute intermittent porphyria in a black South African. The clinical presentation mimicked a progressive lower motor neuron syndrome.