Transcriptomic and Proteomic Analysis of Host-Parasite Interaction in Hepatitis B Virus-Associated Liver Disease Progression in Nigerian Patients

Hepatitis B virus infection is hyperendemic in Nigeria and progresses through stages of chronic hepatitis, liver fibrosis, cirrhosis, and hepatocellular carcinoma in a significant proportion of infected individuals, yet the transcriptomic and proteomic signatures of host-virus interaction determining progression trajectory in Nigerian patients are largely uncharacterized. This dissertation analyses transcriptomic and proteomic changes associated with hepatitis B virus-associated liver disease progression in Nigerian patients, providing an integrated molecular characterisation of host-parasite interaction across disease stages. A cross-sectional cohort at the University of Ibadan study group enrolled liver biopsy specimens and matched plasma from one hundred and sixty participants stratified across five groups: HBsAg-positive immune tolerant carriers, chronic hepatitis B, liver fibrosis, cirrhosis, and hepatocellular carcinoma, plus twenty HBsAg-negative healthy controls. Transcriptomics was performed on liver biopsies by bulk RNA sequencing. Plasma proteomics was conducted by data-independent acquisition mass spectrometry. Viral genome sequencing identified HBV genotype and characterised surface antigen and polymerase mutations affecting immune escape and antiviral resistance. Bioinformatic integration of transcriptomic and proteomic data identified progressive molecular signatures characterising each disease stage transition. Key findings include transcriptional activation of epithelial-mesenchymal transition gene networks at the hepatitis-to-fibrosis transition, concurrent upregulation of the complement lectin pathway at the fibrosis-to-cirrhosis transition, and metabolic-to-oncogenic programming switch at the cirrhosis-to-hepatocellular carcinoma transition. Plasma proteomic signatures at the fibrosis stage identify three candidate early fibrosis biomarkers with AUC values above 0.85 against liver biopsy fibrosis stage as criterion reference. Keywords: hepatitis B virus, liver disease progression, transcriptomics, proteomics, Nigeria.