Hepatitis C infection at a tertiary hospital in South Africa: Clinical presentation, non-invasive assessment of liver fibrosis, and response to therapy.

BACKGROUND: Hepatitis C is a viral infection that leads to chronic liver disease, resulting in significant morbidity and mortality. OBJECTIVES: To describe the demographic characteristics and clinical presentation of patients with chronic hepatitis C infection. The aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis index based on 4 factors (FIB-4) were assessed for prediction of liver fibrosis. METHODS: We retrospectively reviewed 87 records of patients who presented to the liver clinic at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from January 2007 to December 2016. Patients' records were reviewed and analysed using SPSS statistical software version 24. Convenience sampling was used. RESULTS: The patients' mean (standard deviation (SD)) age was 52.6 (12.3) years. Fifty-four percent were female. Hepatitis C virus genotype 5 was exclusively found in blacks (p<0.001), constituting 60.3% of infections in this ethnic group and 48.7% in the cohort, followed by genotype 1 (21.8%), genotype 3 (15.4%), genotype 4 (10.3%) and mixed-genotype infections (3.8%). Genotype 5 patients were older (mean (SD) age 56.7 (9.8) years) than genotype 1 (46.3 (11.4) years) and genotype 3 (42 (9.8) years) (p=0.002 and p<0.001, respectively). The receiver operating characteristic curve for METAVIR F0 v. APRI (cut-off <0.7) showed a moderate correlation, with an area under the curve (AUC) of 0.349 (p=0.002), sensitivity of 78.8%, specificity of 70.6% and a negative predictive value (NPV) of 63.2%. METAVIR F4 v. APRI (cut-off ≥1.5) showed an AUC of 0.881 (p=0.001) with sensitivity of 85.7%, specificity of 93% and a positive predictive value (PPV) of 67%. METAVIR F0 v. FIB-4 (cut-off <1.45) showed a moderate correlation, with an AUC of 0.332 (p=0.021), sensitivity of 78.3%, specificity of 53.8% and an NPV of 73.7%. METAVIR F4 v. FIB-4 (cut-off >3.25) had a strong correlation, with an AUC of 0.952 (p<0.001), sensitivity of 63.6%, specificity of 100% and a PPV of 100%. Early virological response (EVR) was found to predict sustained virological response (SVR) to therapy (odds ratio 27.8; 95% confidence interval 2.8 - 274.3; p=0.004). CONCLUSIONS: Compared with other genotypes, genotype 5 was predominant in our cohort, particularly in older age groups. Moreover, APRI and FIB-4 scores correlated significantly with advanced fibrosis in HCV patients. Finally, EVR during therapy was found to determine SVR.

Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa.

Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ∼ 90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a(N = 10) 1b(N = 12), 3a(N = 5), 4a(N = 3) and 5a(N = 61). Two mutations, associated with interferon resistance-R70Q and T110N-were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC50nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes.