Molecular Basis and Clinical Significance of the High-risk Phenotype of Hepatitis B Virus Genotype C (IMAGE)
Caption
HBV genotype C represents a clinically relevant high-risk form of chronic HBV infection. It is generally associated with delayed HBeAg seroconversion, persistent viral replication, more active hepatic inflammation, faster fibrosis progression, and a higher risk of HCC. Importantly, this risk may persist even after effective antiviral suppression, especially in patients with advanced fibrosis or cirrhosis. The high-risk phenotype of genotype C appears to be related to its viral sequence background, enrichment of BCP/preC/HBx-related variants, altered HBeAg expression, immune dysregulation, HBx-related oncogenic signaling, and HBV integration-associated genomic instability. Although these mechanisms are not exclusive to genotype C, they may be more clinically relevant in genotype C infection because of the prolonged replication phase, enrichment of high-risk viral variants, and greater cumulative inflammatory and oncogenic injury. In clinical practice, genotype C should be viewed as a risk-enhancing virological factor rather than a stand-alone determinant of treatment or surveillance decisions. Combining genotype information with viral mutations, fibrosis stage, cirrhosis status, treatment response, and emerging biomarkers may help refine long-term risk assessment and surveillance planning for patients with chronic hepatitis B.
Credit
Lei Sang, Tao Shen
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CC BY-NC