Quasispecies Variant of Pre-S/S Gene in HBV-related Hepatocellular Carcinoma with HBs Antigen Positive and Occult Infection

Overview

Journal Infect Agent Cancer

Publisher Biomed Central

Specialty Infectious Diseases

Date 2018 Feb 14

PMID 29434654

Citations 9

Authors

Yuri Hatazawa

Yoshihiko Yano

Rina Okada

Toshihito Tanahashi

Hiroki Hayashi

Hirotaka Hirano

Akihiro Minami

Yuki Kawano

Motofumi Tanaka

Takumi Fukumoto

Yoshiki Murakami

Masaru Yoshida

Yoshitake Hayashi

Affiliations

Soon will be listed here.

Abstract

Background: Hepatocellular carcinoma (HCC) can develop in patients who are negative for the hepatitis B surface antigen (HBsAg) in serum but positive for hepatitis B virus (HBV) DNA in the liver, referred to as occult HBV infection (OBI). Previous reports showed that HBV variants in OBI-related HCC are different from those in HBsAg-positive HCC. In the present study, HBV quasispecies based on the pre-S/S gene in OBI-related HCC patients were examined by high throughput sequencing and compared with those in HBsAg-positive HCC.

Methods: Nineteen tissue samples (9 OBI-related and 10 HBsAg-positive non-cancerous tissues) were collected at the time of surgery at Kobe University Hospital. The quasispecies with more than 1% variation in the pre-S/S region were isolated and analysed by ultra-deep sequencing.

Results: There were no significant differences in the major HBV populations, which exhibit more than 20% variation within the entire pre-S/S region, between OBI-related HCC and HBsAg-positive HCC. However, the prevalences of major populations with pre-S2 region mutations and of minor populations with polymerized human serum albumin-binding domain mutations were significantly higher in OBI-related HCC than in HBsAg-positive HCC. Moreover, the major variant populations associated with the B-cell epitope, located within the pre-S1 region, and the a determinant domain, located in the S region, were detected frequently in HBsAg-positive HCC. The minor populations of variants harbouring the W4R, L30S, Q118R/Stop, N123D and S124F/P mutations in the pre-S region and the L21F/S and L42F/S mutations in the S region were detected more frequently in OBI-related HCC than in HBsAg-positive HCC.

Conclusions: Ultra-deep sequencing revealed that the B-cell epitope domain in the pre-S1 region and alpha determinant domain in the S region were variable in HBsAg-positive HCC, although the quasispecies associated with the pre-S2 region were highly prevalent in OBI-related HCC.

Trial Registration: Ref: R000034382/UMIN000030113; Retrospectively registered 25 November 2017.

Citing Articles

Occult Hepatitis B Virus Infection in Hepatic Diseases and Its Significance for the WHO's Elimination Plan of Viral Hepatitis.

Bucio-Ortiz L, Enriquez-Navarro K, Maldonado-Rodriguez A, Torres-Flores J, Cevallos A, Salcedo M Pathogens. 2024; 13(8).

PMID: 39204261 PMC: 11357063. DOI: 10.3390/pathogens13080662.

Occult Hepatitis B Virus Infection: An Update.

Saitta C, Pollicino T, Raimondo G Viruses. 2022; 14(7).

PMID: 35891484 PMC: 9318873. DOI: 10.3390/v14071504.

Association of Increased Programmed Death Ligand 1 Expression and Regulatory T Cells Infiltration with Higher Hepatocellular Carcinoma Recurrence in Patients with Hepatitis B Virus Pre-S2 Mutant after Curative Surgical Resection.

Jeng L, Li T, Hsu S, Teng C Viruses. 2022; 14(6).

PMID: 35746817 PMC: 9229682. DOI: 10.3390/v14061346.

Mutations in the HBV PreS/S gene related to hepatocellular carcinoma in Vietnamese chronic HBV-infected patients.

Huong N, Quang Trung N, Luong B, Tram D, Vu H, Bui H PLoS One. 2022; 17(4):e0266134.

PMID: 35390033 PMC: 8989215. DOI: 10.1371/journal.pone.0266134.

Low Genetic Diversity of Hepatitis B Virus Surface Gene amongst Australian Blood Donors.

Phan N, Faddy H, Flower R, Dimech W, Spann K, Roulis E Viruses. 2021; 13(7).

PMID: 34208852 PMC: 8310342. DOI: 10.3390/v13071275.

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