Hepatitis B and C in Malawi: Epidemiology, Disease Burden and Opportunities for a Public Health Treatment Programme

Stockdale, Alexander
(2020) Hepatitis B and C in Malawi: Epidemiology, Disease Burden and Opportunities for a Public Health Treatment Programme. Doctor of Philosophy thesis, University of Liverpool.

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Abstract In sub-Saharan Africa, hepatitis B virus (HBV) infection is the principal cause of liver cirrhosis and hepatocellular carcinoma (HCC). Mortality from cirrhosis and HCC is projected to rise beyond 2030 unless adult HBV treatment programmes are implemented. Infant HBV vaccination was introduced across sub-Saharan Africa between 1994-2014, and in Malawi in 2002 where it is given at 6, 10 and 14 weeks of life. Hepatitis C virus (HCV) is an important contributor to liver disease globally, with an estimated population prevalence of 1% in sub-Saharan Africa. In Southern Africa there is a paucity of HCV prevalence data, with no previous random probability-sampling community studies. A hospital-based study of cirrhosis and HCC in a tertiary hospital, and seroprevalence studies in an urban township, were conducted in Blantyre, Malawi, to determine HBV and HCV prevalence and HBV vaccine impact. Of 97,386 censused individuals, single stage non-replacement age-stratified probability sampling was used to select 6,073 individuals who were tested for hepatitis B surface antigen (HBsAg) in a community serosurvey. HBsAg-positive individuals aged ≥16 were recruited to assess treatment eligibility. Among individuals aged ≥16 in the serosurvey, 1661 (51%) were randomly selected for HCV antigen/antibody (Ag/Ab) testing with confirmatory HCV RNA PCR. Prevalence estimates were standardised to census age and sex distribution using post-stratification proportional fitting. In the hospital study, the population attributable fraction (PAF) of HBV to cirrhosis and HCC was 23.1% (95% CI 15.7- 29.8) and 71.5% (59.3- 80.1) respectively among 250 consecutively recruited patients. For HCV the PAF was 1.6% (95% CI -0.4 – 3.6) for cirrhosis and 4.8% (-0.1, 9.5) for HCC. Patients with HCC were diagnosed at an advanced stage with a median tumour size of 12.6cm and a median survival of 1.3 months. Six-month survival was 67% (59.0- 73.8) among patients with cirrhosis. Standardised HBsAg prevalence in serosurvey participants born prior to, and after HBV vaccine introduction, was 5.1% (95% CI 4.3- 6.1) and 0.3% (95% CI 0.1- 0.6) respectively. Three-dose vaccination coverage was 97.4% (1141/1171) among 1171/2085 children aged ≤10 years with known vaccine status. By comparison of participants born 5 years before and after vaccine introduction, vaccine impact was 95.9% (95% CI 70.6- 99.4). Treatment eligibility was assessed in 94/150 HBsAg positive people aged ≥16 years from the serosurvey, of whom 24/93 (26%) were HIV positive, and 16/24 (67%) were receiving antiretroviral therapy containing tenofovir, with HBV DNA suppression. Among 69 HIV-negative HBsAg positive individuals, 3,6 and 9% were eligible for HBV treatment by WHO, EASL and AASLD criteria respectively. Standardised HCV Ag/Ab prevalence was 0.78% (95% CI 0.46- 1.33) and HCV RNA prevalence was 0.18% (95% CI 0.06- 0.53). HCV Ag/Ab positive individuals were older than the general population but no differences in sex, educational, employment or marital status were observed. In an urban township in Malawi, HBV prevalence was intermediate at 5.1% among unvaccinated adults. Infant HBV vaccination was associated with a vaccine impact of 96%. Among HBsAg-positive adults, one quarter were HIV-positive and 3-9% of HIV-negative adults were eligible for antiviral therapy. Estimated population HCV RNA prevalence was 0.2%. Future prevalence studies should sample rural communities and specific risk groups. HCC is diagnosed at an advanced stage with a poor prognosis in Malawi, and HBV is an important cause. The burden of HBV and HCV associated liver disease represents both a challenge, and an opportunity to implement public health treatment programmes to reverse rising liver-related mortality in Southern Africa.

Item Type: Thesis (Doctor of Philosophy)
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 18 Aug 2020 10:52
Last Modified: 13 May 2021 07:11
DOI: 10.17638/03079836
URI: https://livrepository.liverpool.ac.uk/id/eprint/3079836