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논문 기본 정보

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학술저널
저자정보
Jeong Won Jang (Department of Internal Medicine College of Medicine The Catholic University of Korea) Jin Seoub Kim (Department of Internal Medicine College of Medicine The Catholic University of Korea) Hye Seon Kim (Department of Internal Medicine College of Medicine The Catholic University of Korea) Kwon Yong Tak (Department of Internal Medicine College of Medicine The Catholic University of Korea) Heechul Nam (Department of Internal Medicine College of Medicine The Catholic University of Korea) Pil Soo Sung (Department of Internal Medicine College of Medicine The Catholic University of Korea) Si Hyun Bae (Department of Internal Medicine College of Medicine The Catholic University of Korea) Jong Young Choi (Department of Internal Medicine College of Medicine The Catholic University of Korea) Seung Kew Yoon (Department of Internal Medicine College of Medicine The Catholic University of Korea) Lewis R. Roberts (Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN USA)
저널정보
대한간학회 Clinical and Molecular Hepatology Clinical and Molecular Hepatology 제27권 제1호
발행연도
2021.1
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207 - 218 (12page)

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Background/Aims: The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance. Methods: Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated. Results: HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC. Conclusions: The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.
#Hepatitis B virus #Virus integration #Liver neoplasms #Hepatitis B surface antigens #Population surveillance

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참고문헌 (18)

참고문헌 신청
Korean Liver Cancer Association / 2019 / 2018 Korean Liver Cancer Association–National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma / Gut and Liver 13(3):227~299 dbpia Bonilla Guerrero R / 2005 / The role of hepatitis B virus integrations in the pathogenesis of human hepatocellular carcinoma / J Hepatol 42:760~777 google schola Budzinska MA / 2018 / Cellular genomic sites of hepatitis B virus DNA integration / Genes (Basel) 9:365 google schola Wong DK / 2020 / Among patients with undetectable hepatitis B surface antigen and hepatocellular carcinoma, a high proportion has integration of HBV DNA into hepatocyte DNA and no cirrhosis / Clin Gastroenterol Hepatol 18:449~456 google schola Tamori A / 2003 / HBV DNA integration and HBV-transcript expression in non-B, non-C hepatocellular carcinoma in Japan / J Med Virol 71:492~498 google schola

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