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Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma.
Liver Int. 2015 Oct; 35(10):2311-7.LI

Abstract

BACKGROUND & AIMS

Hepatitis B virus (HBV) DNA integration in the host genome is a major mechanism responsible for the etiopathogenetic role exerted by HBV in hepatocellular carcinoma (HCC) development. Extensive analyses evaluating viral integration in HBV surface antigen (HBsAg) negative patients with occult HBV infection (OBI) have not yet been performed. The aim of this study was to investigate and characterize HBV DNA integration in HCC tissues from OBI patients.

METHODS

Tumour DNA extracts from 69 HCC patients (49 HBsAg-negative with occult infection diagnosed by HBV DNA detection in tumour tissues; 10 HBsAg-positive and 10 HBsAg-negative/OBI-negative as control groups) were examined by Alu-PCR technique to reveal HBV DNA integration into the host genome. The molecular characterization of the virus-genome junctions was performed by cloning and sequencing analyses.

RESULTS

Integrated HBV DNA was detected in 37/49 (75.5%) OBI-positive HCC samples, in 8/10 (80%) HBsAg-positive and in 0/10 OBI-negative HCC samples. Nine of 37 (24.3%) integrated viral sequences from OBI-positive cases were inside human genome coding regions and in the remaining cases the localization at intergenic level was frequently adjacent to coding genes. Concerning viral integrants in OBI cases, X gene sequences were found in 14 cases, preS/S sequences in 13, Core sequences in 7, and Polymerase gene sequences in three cases.

CONCLUSIONS

In analogy to what occurs in HBsAg-positive cases, HBV DNA integration is highly prevalent in OBI-related HCCs, it mainly involves X and preS/S viral genomic regions and it frequently occurs at the level of regulatory and functional genes.

Authors+Show Affiliations

Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Messina, Italy.Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.Division of Oncological Surgery, Department of General Surgery, Oncology and Pathology, University Hospital of Messina, Messina, Italy.Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.Gastroenterology and Hepatology Division, University of Torino, San Giovanni Battista Hospital, Torino, Italy.Gastroenterology and Hepatology Division, University of Torino, San Giovanni Battista Hospital, Torino, Italy.Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Messina, Italy.Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, "AM & A Migliavacca" Center for the Study of Liver Disease, Milano, Italy.Division of Oncological Surgery, Department of General Surgery, Oncology and Pathology, University Hospital of Messina, Messina, Italy.Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Messina, Italy. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Messina, Italy. Department of Pediatric, Gynecologic, Microbiologic and Biomedical Sciences, University of Messina, Messina, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25677098

Citation

Saitta, Carlo, et al. "Hepatitis B Virus (HBV) DNA Integration in Patients With Occult HBV Infection and Hepatocellular Carcinoma." Liver International : Official Journal of the International Association for the Study of the Liver, vol. 35, no. 10, 2015, pp. 2311-7.
Saitta C, Tripodi G, Barbera A, et al. Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma. Liver Int. 2015;35(10):2311-7.
Saitta, C., Tripodi, G., Barbera, A., Bertuccio, A., Smedile, A., Ciancio, A., Raffa, G., Sangiovanni, A., Navarra, G., Raimondo, G., & Pollicino, T. (2015). Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma. Liver International : Official Journal of the International Association for the Study of the Liver, 35(10), 2311-7. https://doi.org/10.1111/liv.12807
Saitta C, et al. Hepatitis B Virus (HBV) DNA Integration in Patients With Occult HBV Infection and Hepatocellular Carcinoma. Liver Int. 2015;35(10):2311-7. PubMed PMID: 25677098.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma. AU - Saitta,Carlo, AU - Tripodi,Gianluca, AU - Barbera,Adalberto, AU - Bertuccio,Antonio, AU - Smedile,Antonina, AU - Ciancio,Alessia, AU - Raffa,Giuseppina, AU - Sangiovanni,Angelo, AU - Navarra,Giuseppe, AU - Raimondo,Giovanni, AU - Pollicino,Teresa, Y1 - 2015/02/25/ PY - 2014/10/28/received PY - 2015/02/09/accepted PY - 2015/2/14/entrez PY - 2015/2/14/pubmed PY - 2016/7/12/medline KW - Alu-PCR KW - HBV DNA KW - HBsAg-negative KW - HCC KW - viral integrants SP - 2311 EP - 7 JF - Liver international : official journal of the International Association for the Study of the Liver JO - Liver Int. VL - 35 IS - 10 N2 - BACKGROUND & AIMS: Hepatitis B virus (HBV) DNA integration in the host genome is a major mechanism responsible for the etiopathogenetic role exerted by HBV in hepatocellular carcinoma (HCC) development. Extensive analyses evaluating viral integration in HBV surface antigen (HBsAg) negative patients with occult HBV infection (OBI) have not yet been performed. The aim of this study was to investigate and characterize HBV DNA integration in HCC tissues from OBI patients. METHODS: Tumour DNA extracts from 69 HCC patients (49 HBsAg-negative with occult infection diagnosed by HBV DNA detection in tumour tissues; 10 HBsAg-positive and 10 HBsAg-negative/OBI-negative as control groups) were examined by Alu-PCR technique to reveal HBV DNA integration into the host genome. The molecular characterization of the virus-genome junctions was performed by cloning and sequencing analyses. RESULTS: Integrated HBV DNA was detected in 37/49 (75.5%) OBI-positive HCC samples, in 8/10 (80%) HBsAg-positive and in 0/10 OBI-negative HCC samples. Nine of 37 (24.3%) integrated viral sequences from OBI-positive cases were inside human genome coding regions and in the remaining cases the localization at intergenic level was frequently adjacent to coding genes. Concerning viral integrants in OBI cases, X gene sequences were found in 14 cases, preS/S sequences in 13, Core sequences in 7, and Polymerase gene sequences in three cases. CONCLUSIONS: In analogy to what occurs in HBsAg-positive cases, HBV DNA integration is highly prevalent in OBI-related HCCs, it mainly involves X and preS/S viral genomic regions and it frequently occurs at the level of regulatory and functional genes. SN - 1478-3231 UR - https://www.unboundmedicine.com/medline/citation/25677098/Hepatitis_B_virus__HBV__DNA_integration_in_patients_with_occult_HBV_infection_and_hepatocellular_carcinoma_ L2 - https://doi.org/10.1111/liv.12807 DB - PRIME DP - Unbound Medicine ER -