Browsing by Subject "Hepatology"

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    Open Access
    A Decade of Hepatitis C at the UCT/GSH Liver Clinic in the Pre-DAA era
    (2019) Nordien, Rozeena; Sonderup, Mark; Spearman, Wendy
    Background 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.
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    Open Access
    ETD: HBV genotypes at the Groote Schuur Hospital Liver Clinic, Cape Town : genotype and subgenotype prevalence and the influence of ethnicity on treatment outcomes during long term clinical follow-up of patience with chronic HBV infection.
    (2008) Nderu, Michelle W; Dr. H. N Hairwadzi and Dr. H. Smuts
    In the developing world, hepatitis B virus (HBV) is an important cause of acute and chronic liver disease. Two billion people worldwide are infected with the virus and an estimated 350 million who have failed to clear the virus have chronic infection. In Africa, HBV is endemic with 98% of the inhabitants being infected with the virus at some point in their lives. Of these 10% fail to clear the virus. The emergence of HBV-HIV coinfected cases in sub-Saharan Africa adds a new dimension in the management of this disease and highlights the need to understand the pathogenesis and treatment of HBV. HBV genotype A and D have been shown to be present in southern Africa with genotype A generally being the predominant genotype documented in South Africa. This is based on studies carried out in the Gauteng and Kwa-Zulu Natal regions. There is very little prevalence data from the W estem Cape and other provinces and there is no data on the pre-dominant HBV genotype seen in this region. This study investigates the predominant HBV genotype and subgenotypes seen at the Groote Schuur Liver Clinic, Cape Town and the possible correlations between the HBV genotype, race and disease severity. In addition early work investigating the possible presence of lamivudine resistant strains in lamivudine na'ive patients are reported. This is important as the increase in incidence of lamivudine use in HBV-HIV co-infected patients may have potential implications in lamivudine treatment management programmes. 169 chronic HBV patients from all races and age groups were recruited into the study. The HBV DNA levels, HBeAg and HBsAg status were determined as part of their standard management at the Liver Clinic. Two methods were used in combination to identify the HBV genotype of the patient using the conserved S-gene on the HBV genome. The detection of lamivudine resistant mutations on the YMDD motif was determined using nucleotide sequence analysis. The possible correlations between race, HBV genotype, interferon-a (IFN-a) treatment, virological and biochemical parameters were analysed. In this study, 73% of the patients were identified as genotype D, 27% as genotype A with one patient being genotype B2. The subgenotypes D3 and D4 were also identified in the xiii cohort. Although genotype D predominates in the Mixed race this did not reach statistical significance in this study. The genotype B2 patient was an immigrant from Taiwan, in keeping with published data from Asia. The Caucasians were older compared to the other races while the non-Caucasoids presented at an older age and with more severe disease. The Asians showed the best response to IFN-a treatment while the Black Africans had significantly lower ALB levels at presentation compared to the other races. As noted in published literature, high ALT and low HBV DNA levels correlated with a better response to IFN-a treatment. No lamivudine resistant strains were found in the lamivudine nai"ve patients but one YVDD mutation was found in a patient who was on lamivudine therapy. This study shows that genotype D and its subgenotype, D3, is the predominant genotype seen in this urban clinical cohort of patients. The unexpected presence of subgenotype D4 is documented. This interesting observation may be explained by the historically well documented population migration from the Indian and Asian Pacific islands into the Cape Town region. No lamivudine resistant strains present with in the lamivudine nai"ve patients in the clinic indicates that these strains are not yet circulating as there have been reports of the presence of these resistant strains in lamivudine nai"ve patients in South Africa. Gene polymorphisms and socio-economic factors may explain the racial difference with respect to age at HBV diagnosis. The success of IFN-a treatment may be related to the varied genetics of the population.
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    Open Access
    Hepatitis C prevalence in HIV infected heterosexual men and men who have sex with men
    (2018) Gogela, Neliswa Antonia; Sonderup, Mark Wayne; Spearman, C Wendy
    Background: Globally 1% of individuals are infected with hepatitis C virus (HCV). In South Africa (SA), the prevalence ranges between 0.3% - 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 product products. The risk of heterosexually transmission is low but is increased in men who have sex with men (MSM) with co- transmission risk of both HIV and HCV. Objectives: Given a limited local understanding, we sought to better understand HCV characteristics and prevalence in 2 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 obtained via a confidentially administered questionnaire. Participants were screened for HCV after a blood draw and positive HCV Ab tests were tested for HCV RNA. Risk factors associated with HCV seropositivity were determined. Results: Five hundred HIV positive men were recruited; 215 (43%) non-MSM and 285 (57%) MSM, with median age 36 years (IQR 20 – 64) and 37 years (IQR 21 – 56), in the MSM and non-MSM group, respectively, p = NS. Overall, 3.4% (n=17) screened HCV positive, 5.6% (n=16) MSM and 0.5% (n=1) non-MSM, with 82.4% viremic for HCV RNA. In respect to genotype (GT) distribution, 50% were infected with GT1, 14.3% GT4 and 35.7% were GT2. In terms of risk, MSM were more likely to have used drugs (54.4% vs. 30.2%, p<0.001) and to have used all five modes of drugs administration (13% of MSM vs. 0.5% of non- MSM for injected drugs, 36.1% vs. 2.3% inhaled, 10% vs. 0% for the rectal route, 48.1% vs. 28.8% for smoked and 27.4% vs. 2.3% for oral drugs). More MSM than non-MSM (46.3% vs. 16.7%) reported sex whilst using recreational drugs and similarly more MSM (21.4% vs. 14%) reported having sex with a sex worker (SW).Risk factors for HCV seropositivity included drug use history (odds ratio (OR) 6.28, 98% confidence interval (CI). 1.78 – 22.12: p=0.004) and in MSM, sex with SW (OR 5.5, 95% 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). Conclusion: HCV prevalence in HIV positive MSM is higher than previously appreciated or documented in South Africa. Risk factors include injecting 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.
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    Open Access
    A retrospective study assessing the clinical outcomes and costs of acute hepatitis A in Cape Town, South Africa
    (2022-01-11) Patterson, Jenna; Cleary, Susan; Silal, Sheetal P; Hussey, Gregory D; Enoch, Annabel; Korsman, Stephen; Goddard, Elizabeth; Setshedi, Mashiko; Spearman, Wendy C; Kagina, Benjamin M; Muloiwa, Rudzani
    Background While some evidence has been demonstrated the cost-effectiveness of routine hepatitis A vaccination in middle-income countries, the evidence is still limited in other settings including in South Africa. Given this, the evidence base around the cost of care for hepatitis A needs to be developed towards considerations of introducing hepatitis A vaccines in the national immunisation schedule and guidelines. Objectives To describe the severity, clinical outcomes, and cost of hepatitis A cases presenting to two tertiary healthcare centers in Cape Town, South Africa. Methods We conducted a retrospective folder review of patients presenting with hepatitis A at two tertiary level hospitals providing care for urban communities of metropolitan Cape Town, South Africa. Patients included in this folder review tested positive for hepatitis A immunoglobulin M between 1 January 2008 and 1 March 2018. Results In total, 239 folders of hepatitis A paediatric patients < 15 years old and 212 folders of hepatitis A adult patients $$\ge$$ ≥ 15 years old were included in the study. Before presenting for tertiary level care, more than half of patients presented for an initial consultation at either a community clinic or general physician. The mean length of hospital stay was 7.45 days for adult patients and 3.11 days for paediatric patients. Three adult patients in the study population died as a result of hepatitis A infection and 29 developed complicated hepatitis A. One paediatric patient in the study population died as a result of hepatitis A infection and 27 developed complicated hepatitis A, including 4 paediatric patients diagnosed with acute liver failure. The total cost per hepatitis A hospitalisation was $1935.41 for adult patients and $563.06 for paediatric patients, with overhead costs dictated by the length of stay being the largest cost driver. Conclusion More than 1 in every 10 hepatitis A cases (13.3%) included in this study developed complicated hepatitis A or resulted in death. Given the severity of clinical outcomes and high costs associated with hepatitis A hospitalisation, it is important to consider the introduction of hepatitis A immunisation in the public sector in South Africa to potentially avert future morbidity, mortality, and healthcare spending.