title: Significance of the quantitative measurement of the chr16: 51320015 integration site in hepatocytes of patients with chronic hepatitis B.
abstract: The present study reported the presence of a hepatitis B virus (HBV) major integration site (MIS) chr16: 51320015 and discussed the significance of quantitative measurement of this site. A total of 30 hepatitis B e antigen (HBeAg) positive (+) and 30 HBeAg negative (‑) patients with chronic hepatitis B (CHB) were enrolled in the present study, and the levels of intrahepatic (IH) covalently closed circular DNA (cccDNA), serum HBV DNA and hepatitis B surface antigen (HBsAg) were detected. Conventional reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and Sanger sequencing were designed to verify the chr16: 51320015 integration site, and the copy numbers of this site were measured using molecular clone and SYBR Green I RT‑qPCR. This site was found to be present in the hepatocytes of all the enrolled patients, and the average number of copies was 1.46x10‑2 ± 4.94x10‑2 copies/cell (3.48x10‑5‑0.212 copies/cell). No significant difference in the copy numbers of this site were observed between the HBeAg (+) (1.43 ± 9.79x10‑1 copies/cell) and HBeAg (‑) patients (6.58x10‑2 ± 2.47x10‑2 copies/cell; P>0.05), which were positively correlated with the levels of serum HBsAg (P=0.0038), but were not correlated with the levels of IH cccDNA (P=0.7785). In conclusion, the chr16:51320015 integration site may be a novel site, which persists in a several patients with HBV infection, and may accumulate in the hepatocytes due to clonal expansion. The diagnostic and therapeutic values of this site require further investigation.
authors.affiliation: Department of Gastroenterology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ruan
authors.affiliation: Department of Gastroenterology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Gastroenterology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Zequn
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D004270:DNA, Circular / Q000032:analysis / Q000235:genetics; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016662:Virus Integration; D055815:Young Adult
chemical_list: D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens