Title of degree: PhD
Title of the type A grant: Prevalence of Mutations in Basal Core Promoter/Precore and pre-S regions of Hepatitis B Virus in Black South Africans with and without Hepatocellular Carcinoma
Name of PI: Prof Anna Kramvis of the University of the Witwatersrand
Epidemiology and Risk Factors associated with Liver Cancer in South Africa
D. Mak1, C. Babb de Villiers2, 3, M. Sengayi3, W. C. Chen3, 4, C. Chasela5, M. I. Urban 3 , E. Singh3, A. Kramvis1*
- Hepatitis Virus Diversity Research Unit, University of the Witwatersrand, Johannesburg, South Africa
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
- National Cancer Registry, National Health Laboratory Service
- Sydney Brenner Institute for Molecular Bioscience
- Department of Epidemiology and Biostatistics, University of the Witwatersrand, Johannesburg, South Africa
Hepatocellular carcinoma (HCC), the most common subtype of liver cancer (LC), is a public health problem in South Africa (SA), with poorly described epidemiology, especially in sub-Saharan Africa. Our aim was to determine the LC mortality trend nationwide (using Statistics South Africa data) and to determine the prevalence of risk factors in a hospital cohort.
Joinpoint trends were computed for the most recent LC mortality data nationwide. The mortality-to-incidence ratios (MIRs) were calculated as the age-adjusted mortality rate divided by the age-adjusted incidence rate. Additionally, a matched case-control analysis of 150 black Africans with HCC, seen at Johannesburg public hospitals from 2000-2012, was undertaken. Demographics, lifestyle behaviours and hepatitis B virus (HBV) molecular characteristics were investigated. Odds ratios (ORs) adjusted for age, year of diagnosis, marital status, place of birth and selected modifiable risk factors were calculated.
From 1999-2015, while the overall LC mortality significantly decreased in SA men (-4.9%) and women (-2.7%), mortality rates increased among 50-69 year old black African women (+2.6% and +6.3%, p<0.05) in recent years. The mortality rates and MIR in black Africans were greater than in their white counterparts in all age groups. HCC was significantly (p<0.05) associated with: rural birthplace, men, living in an urban area for <14 years, HBV DNA + /HBsAg + (OR 34.5), HBV DNA + /HBsAg – (OR 3.76), HBV DNA level >2000 IU/ml (OR 8.55) to ≥200,000 (OR 16.93), anti-HCV (OR 8.98), HBV DNA + /HIV + co-infection (OR 5.36). Infection with HIV alone and modifiable risk factors (alcohol consumption, tobacco smoking, number of sexual partners, diabetes and hormonal contraceptive use) were not associated with HCC. Phylogenetic analysis of the complete surface gene of HBV showed that majority (90.7%) of isolates belonged to subgenotype A1. In HCC cases HBV with 1753C/G (22.5.4%), 1764A (69.4%) and pre-S2:F22L (51.5%), and pre-S deletion mutations were significantly more prevalent than in controls (p<0.05).
Decreasing LC mortality rates among the younger and an increase in rates in the older black Africans suggest that the nadir of the disease may be near or may have passed. A considerable portion of the HCC burden falls on rural migrants to urban areas, most of whom are men and HBV remains a primary risk factor.
Disclosure of Interest: None Declared