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Hepatitis B virus DNA integration in hepatocellular carcinoma after interferon-induced disappearance of hepatitis C virus.
Am J Gastroenterol 2005; 100(8):1748-53AJ

Abstract

OBJECTIVES

Hepatocellular carcinoma (HCC) has been reported in patients in whom hepatitis C virus (HCV) was eliminated by interferon (IFN) therapy. We examined the pathogenesis of HCC in patients with sustained viral response.

METHODS

Operable HCC developed in 7 of 342 patients cured of HCV infection by IFN monotherapy. No patient abused alcohol or had diabetes mellitus or obesity. Resected specimens of HCC were histologically evaluated. DNA extracted from HCC was examined by polymerase chain reaction (PCR) to locate hepatitis B virus (HBV) DNA. HBV integration sites in human genome were identified by cassette-ligation-mediated PCR.

RESULTS

HBV DNA was not amplified in serum samples from any of the seven patients with HCC and was found in liver in four patients. In the latter four patients, HBV DNA was integrated into the human genome of HCC. In two of these patients, covalently closed circular HBV (cccHBV) was also detected. The patients with HBV DNA integration were free of HCV for more than 3 yr. In two of the three patients without HBV DNA integration, the surrounding liver showed cirrhosis. The liver of HCC with HBV DNA integration had not progressed to cirrhosis. Three of the four tumors with HBV integration had one integration site each, located at chromosomes 11q12, 11q22-23, and 22q11, respectively. The other tumor had two integration sites, situated at chromosomes 11q13 and 14q32. At chromosome 11q12, HBV DNA was integrated into protein-coding genome, the function of which remains unclear.

CONCLUSION

Integrated HBV DNA may play a role in hepatocarcinogenesis after the clearance of HCV by IFN treatment.

Authors+Show Affiliations

Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Pub Type(s)

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

Language

eng

PubMed ID

16086711

Citation

Tamori, Akihiro, et al. "Hepatitis B Virus DNA Integration in Hepatocellular Carcinoma After Interferon-induced Disappearance of Hepatitis C Virus." The American Journal of Gastroenterology, vol. 100, no. 8, 2005, pp. 1748-53.
Tamori A, Nishiguchi S, Shiomi S, et al. Hepatitis B virus DNA integration in hepatocellular carcinoma after interferon-induced disappearance of hepatitis C virus. Am J Gastroenterol. 2005;100(8):1748-53.
Tamori, A., Nishiguchi, S., Shiomi, S., Hayashi, T., Kobayashi, S., Habu, D., ... Kubo, S. (2005). Hepatitis B virus DNA integration in hepatocellular carcinoma after interferon-induced disappearance of hepatitis C virus. The American Journal of Gastroenterology, 100(8), pp. 1748-53.
Tamori A, et al. Hepatitis B Virus DNA Integration in Hepatocellular Carcinoma After Interferon-induced Disappearance of Hepatitis C Virus. Am J Gastroenterol. 2005;100(8):1748-53. PubMed PMID: 16086711.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatitis B virus DNA integration in hepatocellular carcinoma after interferon-induced disappearance of hepatitis C virus. AU - Tamori,Akihiro, AU - Nishiguchi,Shuhei, AU - Shiomi,Susumu, AU - Hayashi,Takehiro, AU - Kobayashi,Sawako, AU - Habu,Daiki, AU - Takeda,Tadashi, AU - Seki,Shuichi, AU - Hirohashi,Kazuhiro, AU - Tanaka,Hiromu, AU - Kubo,Shoji, PY - 2005/8/10/pubmed PY - 2005/10/6/medline PY - 2005/8/10/entrez SP - 1748 EP - 53 JF - The American journal of gastroenterology JO - Am. J. Gastroenterol. VL - 100 IS - 8 N2 - OBJECTIVES: Hepatocellular carcinoma (HCC) has been reported in patients in whom hepatitis C virus (HCV) was eliminated by interferon (IFN) therapy. We examined the pathogenesis of HCC in patients with sustained viral response. METHODS: Operable HCC developed in 7 of 342 patients cured of HCV infection by IFN monotherapy. No patient abused alcohol or had diabetes mellitus or obesity. Resected specimens of HCC were histologically evaluated. DNA extracted from HCC was examined by polymerase chain reaction (PCR) to locate hepatitis B virus (HBV) DNA. HBV integration sites in human genome were identified by cassette-ligation-mediated PCR. RESULTS: HBV DNA was not amplified in serum samples from any of the seven patients with HCC and was found in liver in four patients. In the latter four patients, HBV DNA was integrated into the human genome of HCC. In two of these patients, covalently closed circular HBV (cccHBV) was also detected. The patients with HBV DNA integration were free of HCV for more than 3 yr. In two of the three patients without HBV DNA integration, the surrounding liver showed cirrhosis. The liver of HCC with HBV DNA integration had not progressed to cirrhosis. Three of the four tumors with HBV integration had one integration site each, located at chromosomes 11q12, 11q22-23, and 22q11, respectively. The other tumor had two integration sites, situated at chromosomes 11q13 and 14q32. At chromosome 11q12, HBV DNA was integrated into protein-coding genome, the function of which remains unclear. CONCLUSION: Integrated HBV DNA may play a role in hepatocarcinogenesis after the clearance of HCV by IFN treatment. SN - 0002-9270 UR - https://www.unboundmedicine.com/medline/citation/16086711/Hepatitis_B_virus_DNA_integration_in_hepatocellular_carcinoma_after_interferon_induced_disappearance_of_hepatitis_C_virus_ L2 - http://Insights.ovid.com/pubmed?pmid=16086711 DB - PRIME DP - Unbound Medicine ER -