Quasispecies variant of pre-S/S gene in HBV-related hepatocellular carcinoma with HBs antigen positive and occult infection

• Published in: Infectious agents and cancer Vol. 13; no. 1; p. 7
• Main Authors: Hatazawa, Yuri, Yano, Yoshihiko, Okada, Rina, Tanahashi, Toshihito, Hayashi, Hiroki, Hirano, Hirotaka, Minami, Akihiro, Kawano, Yuki, Tanaka, Motofumi, Fukumoto, Takumi, Murakami, Yoshiki, Yoshida, Masaru, Hayashi, Yoshitake
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02-02-2018; BioMed Central; BMC
• Subjects: Development and progression; HBV; HCC; Health aspects; Hepatitis B virus; Hepatocellular carcinoma; Infection; Occult; Pre-S/S; Quasispecies; Ultra-deep sequencing; Quasispecies; HCC; Pre-S/S; Ultra-deep sequencing; HBV; Occult
• ISSN: 1750-9378; 1750-9378
• DOI: 10.1186/s13027-018-0179-4

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