The impact of single-nucleotide variants of hepatitis B virus and antiviral on liver cancer in gray zone patients.

Abstract

Objectives: This study investigated the impact and related mechanisms of single-nucleotide variants (SNVs) in the HBV pre-S/S region on tumor development, and evaluated the role of antiviral therapy.

Methods: A retrospective analysis was conducted in 104 patients of the gray zone. HCC-associated SNVs were analyzed in baseline samples.

Results: HCC occurred in 15 patients (14.4%) during the median follow-up period of 10.4 years. Genotype B HBV-infected HCC patients had more T53C, A273G, and A529G SNVs and genotype C HBV-infected HCC patients had more T53C, G633A, and A3120G SNVs than HCC-free groups. Antiviral therapy reduced the risk of HCC in patients with HCC-associated SNVs in the gray zone both genotype B or C. Ectopic expression of replication-competent HBV plasmids in Huh7 cells expressing HCC-associated SNVs resulted in greater impairment of mitochondrial dynamics, increased production of reactive oxygen species (ROS), decreased mitochondrial membrane potential, lower ATP production, higher basal calcium levels, and reduced calcium buffering capacity compared to controls or wild-type HBV-expressing cells.

Conclusions: CHB patients in the gray zone remain at risk for HCC owing to both wild-type and HCC-associated HBV SNVs, especially the latter, inducing mitochondrial and metabolic dysfunctions. Antiviral therapy reduces the risk of HCC development in these patients.