Quantification of Pregenomic RNA and Covalently Closed Circular DNA in Hepatitis B Virus-Related Hepatocellular Carcinoma

Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and...

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Main Authors: Fugui Bai, Yoshihiko Yano, Takumi Fukumoto, Atsushi Takebe, Motofumi Tanaka, Kaori Kuramitsu, Nungki Anggorowati, Hanggoro Tri Rinonce, Dewiyani Indah Widasari, Masaya Saito, Hirotaka Hirano, Takanobu Hayakumo, Yasushi Seo, Takeshi Azuma, Yonson Ku, Yoshitake Hayashi
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:International Journal of Hepatology
Online Access:http://dx.doi.org/10.1155/2013/849290
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author Fugui Bai
Yoshihiko Yano
Takumi Fukumoto
Atsushi Takebe
Motofumi Tanaka
Kaori Kuramitsu
Nungki Anggorowati
Hanggoro Tri Rinonce
Dewiyani Indah Widasari
Masaya Saito
Hirotaka Hirano
Takanobu Hayakumo
Yasushi Seo
Takeshi Azuma
Yonson Ku
Yoshitake Hayashi
author_facet Fugui Bai
Yoshihiko Yano
Takumi Fukumoto
Atsushi Takebe
Motofumi Tanaka
Kaori Kuramitsu
Nungki Anggorowati
Hanggoro Tri Rinonce
Dewiyani Indah Widasari
Masaya Saito
Hirotaka Hirano
Takanobu Hayakumo
Yasushi Seo
Takeshi Azuma
Yonson Ku
Yoshitake Hayashi
author_sort Fugui Bai
collection DOAJ
description Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P<0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.
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spelling doaj-art-faf48e08392c41d3a36b494945d79adb2025-02-03T01:23:33ZengWileyInternational Journal of Hepatology2090-34482090-34562013-01-01201310.1155/2013/849290849290Quantification of Pregenomic RNA and Covalently Closed Circular DNA in Hepatitis B Virus-Related Hepatocellular CarcinomaFugui Bai0Yoshihiko Yano1Takumi Fukumoto2Atsushi Takebe3Motofumi Tanaka4Kaori Kuramitsu5Nungki Anggorowati6Hanggoro Tri Rinonce7Dewiyani Indah Widasari8Masaya Saito9Hirotaka Hirano10Takanobu Hayakumo11Yasushi Seo12Takeshi Azuma13Yonson Ku14Yoshitake Hayashi15Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanCenter for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanCenter for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanCenter for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanCenter for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanCenter for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanPregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P<0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.http://dx.doi.org/10.1155/2013/849290
spellingShingle Fugui Bai
Yoshihiko Yano
Takumi Fukumoto
Atsushi Takebe
Motofumi Tanaka
Kaori Kuramitsu
Nungki Anggorowati
Hanggoro Tri Rinonce
Dewiyani Indah Widasari
Masaya Saito
Hirotaka Hirano
Takanobu Hayakumo
Yasushi Seo
Takeshi Azuma
Yonson Ku
Yoshitake Hayashi
Quantification of Pregenomic RNA and Covalently Closed Circular DNA in Hepatitis B Virus-Related Hepatocellular Carcinoma
International Journal of Hepatology
title Quantification of Pregenomic RNA and Covalently Closed Circular DNA in Hepatitis B Virus-Related Hepatocellular Carcinoma
title_full Quantification of Pregenomic RNA and Covalently Closed Circular DNA in Hepatitis B Virus-Related Hepatocellular Carcinoma
title_fullStr Quantification of Pregenomic RNA and Covalently Closed Circular DNA in Hepatitis B Virus-Related Hepatocellular Carcinoma
title_full_unstemmed Quantification of Pregenomic RNA and Covalently Closed Circular DNA in Hepatitis B Virus-Related Hepatocellular Carcinoma
title_short Quantification of Pregenomic RNA and Covalently Closed Circular DNA in Hepatitis B Virus-Related Hepatocellular Carcinoma
title_sort quantification of pregenomic rna and covalently closed circular dna in hepatitis b virus related hepatocellular carcinoma
url http://dx.doi.org/10.1155/2013/849290
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