Work

Hepatitis B virus-associated hepatocellular carcinoma in South Africa: epidemiology and impact of HIV-1 co-infection and immune dysregulation

Year: 2016
Type: dissertation
Study design: Observational Study
Abstract: Co-infection with the human immunodeficiency virus (HIV) negatively impacts the natural progression of hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis and hepatocellular carcinoma (HCC).In sub-Saharan Africa the overlap between high HIV and HBV prevalence may increase the incidence of HCC.The aim of this study was to investigate the effect of HIV co-infection on presentation of HCC among HBV-infected patients.Since HCC is thought to be driven by ongoing severe inflammation, the study also evaluated the association between the expression of markers of immune activation/exhaustion and liver inflammation in patients with chronic hepatitis B (CHB) to determine if the risk of hepatofibrosis is increased by exposure to gut microbial products and compared HIV-infected patients with HBV-infected and HIV-HBV co-infected patients.Ethical approval was obtained to conduct two sub-studies.The first sub-study (HCC Epidemiology Study) involved recruitment of patients diagnosed with HCC at oncology units of selected teaching hospitals in South Africa.A total of 107 HCC cases were recruited between December 2012 and October 2015.Demographic, laboratory and clinical data together with blood specimens were collected.Patients were tested for HBV, hepatitis C virus (HCV) and HIV.Molecular characterization of HBV and HCV was also performed.For the second sub-study (Liver Fibrosis and Immune Markers Study), 46 HBV/HIV co-infected; 47 HBV monoinfected; 39 HIV monoinfected and; 39 HIV-/HBV-uninfected controls were recruited following informed consent.All HIV-infected patients had been on highly active antiretroviral therapy (HAART) for ≥3 months.Liver stiffness measurements were taken using the Fibroscan 402.Cell-based immunomarkers of activation/exhaustion were measured using flow cytometry of fresh whole blood.Soluble serum/plasma immunomarkers were measured using ELISA and Luminex.HIV and HBV viral loads and genotyping of HBV were performed.Of 107 cases in the HCC Epidemiology study, 83 (78%) were male and 68/106 (64%, 95% CI: 59-77) were positive for HBsAg.HIV seropositivity was seen in 22/100 (22%, 95% CI: 14-30) of all HCC cases.Among HBsAg-positive HCC cases, 19/66 (29%, 95% CI: 18-40) were HIV-infected compared to only 3/34 (9%) among those that were HBsAg-negative, p=0.04.The proportion of females among the HBV/HIV co-infected HCC cases 6/18 (33%, 95% CI: 11-55) was significantly higher compared to those that were HBV-mono-infected 6/47 (13%, 95% CI: 3-23), p=0.005.HIV/HBV co-infected females presented younger, at Stellenbosch University https://scholar.sun.ac.za
Language: English
Subfield: Epidemiology
Field: Medicine
Open Access status: green
OpenAlex ID: W2582351561
Cites: 416
Cited by: 1
Related to: 10