Background
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in Ghana, largely driven by chronic hepatitis B virus (HBV) infection. Beyond genetic mutations, HBV promotes hepatocarcinogenesis through epigenetic alterations and metabolic reprogramming, particularly dysregulation of glycolysis and related enzymes. However, data linking HBV-associated epigenetic changes, microRNA dysregulation, and altered glycolytic pathways in HCC within low- and middle-income country (LMIC) settings such as Ghana remain limited. Understanding these mechanisms in the local context is essential for identifying relevant biomarkers and therapeutic targets.

Objectives
This study aims to investigate the role of key glycolytic enzymes (HK2, G6PD, PKM2, and LDHA) in HBV-associated HCC in Ghana, with a focus on their transcriptional, protein, and functional alterations. It further seeks to explore the contribution of epigenetic regulation, including DNA methylation and microRNA dysregulation, to metabolic reprogramming and potential drug resistance in HCC.

Methods
The study uses an LMIC-led, hospital-based design involving HCC patients with and without HBV infection in Ghana. Formalin-fixed paraffin-embedded (FFPE) and, where available, fresh liver tissue samples are analyzed. mRNA expression is assessed using quantitative PCR, while protein levels are evaluated by immunohistochemistry and/or Western blotting. Enzymatic activity assays are performed for selected targets. DNA methylation analysis of glycolytic gene promoters is conducted using bisulfite-based methods, alongside targeted microRNA profiling. Clinical and pathological data are integrated to examine associations with disease characteristics. All laboratory work, data generation, and primary interpretation are conducted locally, with supportive technical input where necessary.

Results
The study is expected to demonstrate upregulation of key glycolytic enzymes in HBV-associated HCC compared to non-HBV liver tissues, reflecting enhanced glycolytic flux. These changes are anticipated to correlate with epigenetic modifications and altered microRNA expression, supporting a mechanistic link between HBV infection, metabolic reprogramming, and tumor progression. Findings will provide context-specific molecular evidence from Ghanaian patients.

Conclusions/Implications for practice or policy
This work will generate locally relevant evidence on the metabolic and epigenetic landscape of HBV-associated HCC in Ghana. The findings may inform the development of context-appropriate biomarkers for prognosis and treatment response, support HBV-focused cancer prevention strategies, and strengthen local research capacity. Ultimately, the study contributes to evidence-based policy and precision oncology approaches tailored to LMIC settings.