Diagnosis, treatment and prevention of hepatitis B virus infection in Kilifi, Kenya

Thesis

Hepatitis B virus (HBV) infection is a global health disaster with an estimated 254 million people chronically infected worldwide leading to over 1 million deaths annually, despite cheap, effective treatment and prevention measures being available. The WHO African Region (WHO-AFR) is particularly affected with over 700,000 new HBV infections occurring in 2022. Unfortunately HBV research in WHO-AFR has historically been poorly funded, and many countries lack access to even basic diagnostics and treatment. Kenya has no viral hepatitis national strategic plan, minimal routine HBV testing, and no guidelines in line with the World Health Organisation. This thesis presents analyses undertaken to understand the burden of HBV infection in Kenya, along with several real world studies implementing HBV testing, vaccination and qualitative work in a County Hospital in Kenya.

HBV prevalence was estimated using systematic review and meta-analyses of existing studies reporting HBV prevalence in Kenya, along with analysing clinical trial data from KEMRI-Wellcome Trust Research Programme. This showed HBV prevalence varies dramatically depending on the population screened, and that there is a large amount of information that could be gleaned from clinical trials, but is not routinely collated or reported.

The STRIKE-HBV study tested adults attending Kilifi County Referral Hospital (KCRH) for HBV, and undertook liver health assessment on 200 individuals testing HBsAg positive and negative. A family history of liver disease and body scarification were identified as risk factors for HBsAg positivity. Next generation HBV sequencing showed closely related familial HBV sequences along with potential tenofovir resistance mutations. Focus group discussions illustrated minimal HBV knowledge prior to the STRIKE-HBV study, along with significant confusion between HBV and HIV. Stigma and economic factors were identified as the biggest barriers to accessing HBV care.

The HepB-Boost study showed around two thirds of healthcare workers at KCRH were unvaccinated against HBV and that implementing free HBV vaccination at KCRH was feasible and well received.

This work has clinical relevance both in Kenya and further afield. It has generated the most comprehensive description of a population living with HBV in WHO-AFR and has demonstrated ways in which clinical care pathways can be improved. It highlights avenues for novel research into HBV genomics and transmission pathways and illustrates the urgent need for better investment in HBV clinical studies in WHO-AFR.

Authors: Downs, L

• DOI: 10.5287/ora-jxgznoggw
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: social stigma; epidemiology; HBV; next generation sequencing; Kenya; occupational health; chronic hepatitis B virus infection; hepatitis B virus; implementation science; advocacy; vaccination
• Subjects: Genomics; Implementation science; Hepatitis B virus; Medical virology; High-throughput nucleotide sequencing; Hepatitis B--Vaccination