The impact of single-nucleotide variants of hepatitis B virus and antiviral on liver cancer in gray zone patients
Year: 2025
Type: article
Study design: Observational Study
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.
Source: Journal of Biomedical Science
Authors: Wei Teng, Ting-Tsung Chang, Chien-Wei Su, Jun-Hao Xu, Chiu-Chi Hsu, Yu-Cheng Chang, Wen-Chun Liu, Yu-Wei Chiou, Yu-Chuan Chang, Yuh-Jin Liang, Jaw-Ching Wu
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funders: National Science and Technology Council, Ministry of Health and Welfare, Ministry of Education, Academia Sinica, Shanghai Educational Development Foundation, Ministry of Education, India, Chang Gung Medical Foundation, Taipei Veterans General Hospital, National Science and Technology Council
Awards: G1021266595, Exploring Sphingolipid Signaling Mediated by Lysosomal Sphingolipid Activator Proteins on Regulating Hbv Replication and Secretory Pathway for Potential Intervention Strategy in Hbv-Associated Hcc, G2160532886, G2275093490, G2287216303, G2510564735, G2715893851, G331069940, G3371343049, G3797758061, G4339031779, The Role of Hbv Replication on Lipid Dysregulation, Mitochondrial Dysfunction and Hcc: a Study of Hybrid Mice of Hbv Transgene and Mir-122 Heterozygous Knockout( II ), G4678860634, Development of a Novel Lamp Pcr Diagnostic Method for Epidemiology and Prevention of Hepatitis D Vi Rus Infection in Mongolia( III ), Investigate the Role and Mechanisms of Microrna on Usp22 and Abcc1 in Multiple Kinase Inhibitor-Resistant Hepatocellular Carcinoma for Innovative and Combination Treatments( I ), G5779553922, The Role of Hbv Replication on Lipid Dysregulation, Mitochondrial Dysfunction and Hcc: a Study of Hybrid Mice of Hbv Transgene and Mir-122 Heterozygous Knockout( III ), G8128000271, G8396154264, G8831943974, G8992919257
OpenAlex ID: W4416832750