Organization WH. Global Hepatitis Report, Geneva; 2017.
Hadziyannis SJ. Natural history of chronic hepatitis B in Euro-Mediterranean and African countries. J Hepatol. 2011;55(1):183–91.
Article
PubMed
Google Scholar
Madihi S, Syed H, Lazar F, Zyad A, Benani A. A systematic review of the current hepatitis B viral infection and hepatocellular carcinoma situation in mediterranean countries. Biomed Res Int. 2020;2020:7027169.
PubMed
PubMed Central
Google Scholar
Liaw YF, Brunetto MR, Hadziyannis S. The natural history of chronic HBV infection and geographical differences. Antivir Ther. 2010;15(Suppl 3):25–33.
Article
PubMed
Google Scholar
Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015;64(12):1972–84.
Article
CAS
PubMed
Google Scholar
Tsukuda S, Watashi K. Hepatitis B virus biology and life cycle. Antiviral Res. 2020;182:104925.
Article
CAS
PubMed
Google Scholar
Hadziyannis E, Hadziyannis S. Current practice and contrasting views on discontinuation of nucleos(t)ide analog therapy in chronic hepatitis B. Expert Rev Gastroenterol Hepatol. 2020;14(4):243–51.
Article
CAS
PubMed
Google Scholar
Jansen L, Kootstra NA, van Dort KA, Takkenberg RB, Reesink HW, Zaaijer HL. Hepatitis B virus pregenomic RNA is present in virions in plasma and is associated with a response to pegylated interferon alfa-2a and nucleos(t)ide analogues. J Infect Dis. 2016;213(2):224–32.
Article
CAS
PubMed
Google Scholar
Wang J, Shen T, Huang X, Kumar GR, Chen X, Zeng Z, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J Hepatol. 2016;65(4):700–10.
Article
CAS
PubMed
Google Scholar
Laras A, Kostamena A, Hadzivannis S. HBV cccDNA, pregenomic RNA and total HBV DNA levels in the liver of HBeAg-negative CHB patients under long term antiviral therapy. EASL J Hepatol. 2007; S28.
Lai CL, Wong D, Ip P, Kopaniszen M, Seto WK, Fung J, et al. Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B. J Hepatol. 2017;66(2):275–81.
Article
CAS
PubMed
Google Scholar
Hadziyannis E, Laras A. Viral biomarkers in chronic HBeAg negative HBV infection. Genes (Basel). 2018;9(10).
Liu S, Zhou B, Valdes JD, Sun J, Guo H. Serum hepatitis B virus RNA: a new potential biomarker for chronic hepatitis B virus infection. Hepatology. 2019;69(4):1816–27.
Article
PubMed
Google Scholar
Laras A, Koskinas J, Hadziyannis SJ. In vivo suppression of precore mRNA synthesis is associated with mutations in the hepatitis B virus core promoter. Virology. 2002;295(1):86–96.
Article
CAS
PubMed
Google Scholar
Laras A, Koskinas J, Dimou E, Kostamena A, Hadziyannis SJ. Intrahepatic levels and replicative activity of covalently closed circular hepatitis B virus DNA in chronically infected patients. Hepatology. 2006;44(3):694–702.
Article
CAS
PubMed
Google Scholar
Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560–99.
Article
PubMed
Google Scholar
Liu Y, Jiang M, Xue J, Yan H, Liang X. Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection. BMC Gastroenterol. 2019;19(1):53.
Article
PubMed
PubMed Central
Google Scholar
Liu Y, Jia M, Wu S, Jiang W, Feng Y. Predictors of relapse after cessation of nucleos(t)ide analog treatment in HBeAg-negative chronic hepatitis B patients: a meta-analysis. Int J Infect Dis. 2019;86:201–7.
Article
PubMed
Google Scholar
Ji X, Xia M, Zhou B, Liu S, Liao G, Cai S, et al. Serum hepatitis B virus RNA levels predict HBeAg seroconversion and virological response in chronic hepatitis B patients with high viral load treated with nucleos(t)ide analog. Infect Drug Resist. 2020;13:1881–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fan R, Zhou B, Xu M, Tan D, Niu J, Wang H, et al. Association between negative results from tests for HBV DNA and RNA and durability of response after discontinuation of nucles(t)ide analogue therapy. Clin Gastroenterol Hepatol. 2020;18(3):719-27.e7.
Article
CAS
PubMed
Google Scholar
Liu YY, Liang XS. Progression and status of antiviral monitoring in patients with chronic hepatitis B: from HBsAg to HBV RNA. World J Hepatol. 2018;10(9):603–11.
Article
PubMed
PubMed Central
Google Scholar
Fylaktou A, Asimina F, Papaventsis D, Dimitrios P, Daoudaki M, Maria D, et al. Molecular epidemiology of chronic hepatitis B virus infection in Greece. J Med Virol. 2011;83(2):245–52.
Article
CAS
PubMed
Google Scholar
Carman WF, Jacyna MR, Hadziyannis S, Karayiannis P, McGarvey MJ, Makris A, et al. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet. 1989;2(8663):588–91.
Article
CAS
PubMed
Google Scholar
Funk ML, Rosenberg DM, Lok AS. World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated precore and core promoter variants. J Viral Hepat. 2002;9(1):52–61.
Article
CAS
PubMed
Google Scholar
Buckwold VE, Xu Z, Chen M, Yen TS, Ou JH. Effects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication. J Virol. 1996;70(9):5845–51.
Article
CAS
PubMed
PubMed Central
Google Scholar
Günther S, Piwon N, Will H. Wild-type levels of pregenomic RNA and replication but reduced pre-C RNA and e-antigen synthesis of hepatitis B virus with C(1653) –> T, A(1762) –> T and G(1764) –> A mutations in the core promoter. J Gen Virol. 1998;79(Pt 2):375–80.
Article
PubMed
Google Scholar
Moriyama K, Okamoto H, Tsuda F, Mayumi M. Reduced precore transcription and enhanced core-pregenome transcription of hepatitis B virus DNA after replacement of the precore-core promoter with sequences associated with e antigen-seronegative persistent infections. Virology. 1996;226(2):269–80.
Article
CAS
PubMed
Google Scholar
Prakash K, Rydell GE, Larsson SB, Andersson M, Norkrans G, Norder H, et al. High serum levels of pregenomic RNA reflect frequently failing reverse transcription in hepatitis B virus particles. Virol J. 2018;15(1):86.
Article
PubMed
PubMed Central
Google Scholar
Butler EK, Gersch J, McNamara A, Luk KC, Holzmayer V, de Medina M, et al. Hepatitis B virus serum DNA and RNA levels in nucleos(t)ide analog-treated or untreated patients during chronic and acute infection. Hepatology. 2018;68(6):2106–17.
Article
CAS
PubMed
Google Scholar
van Campenhout MJH, van Bömmel F, Pfefferkorn M, Fischer J, Deichsel D, Boonstra A, et al. Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment. Hepatology. 2018;68(3):839–47.
Article
PubMed
Google Scholar
Su Q, Wang SF, Chang TE, Breitkreutz R, Hennig H, Takegoshi K, et al. Circulating hepatitis B virus nucleic acids in chronic infection: representation of differently polyadenylated viral transcripts during progression to nonreplicative stages. Clin Cancer Res. 2001;7(7):2005–15.
CAS
PubMed
Google Scholar
Gu Y, Chen L, Lian Y, Gu L, Chen Y, Bi Y, et al. Serum HBV pregenomic RNA is correlated with Th1/Th2 immunity in treatment-naïve chronic hepatitis B patients. J Med Virol. 2020;92(3):317–28.
Article
CAS
PubMed
Google Scholar
Chen Y, Sze J, He ML. HBV cccDNA in patients’ sera as an indicator for HBV reactivation and an early signal of liver damage. World J Gastroenterol. 2004;10(1):82–5.
Article
PubMed
PubMed Central
Google Scholar
Wong DK, Yuen MF, Yuan H, Sum SS, Hui CK, Hall J, et al. Quantitation of covalently closed circular hepatitis B virus DNA in chronic hepatitis B patients. Hepatology. 2004;40(3):727–37.
Article
CAS
PubMed
Google Scholar
Liu S, Liu Z, Li W, Zhou B, Liang X, Fan R, et al. Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues. Aliment Pharmacol Ther. 2020;52(4):692–700.
Article
CAS
PubMed
Google Scholar
Wang ML, Liao J, Ye F, Tao YC, Wu DB, He M, et al. Distribution and factors associated with serum HBV pregenomic RNA levels in Chinese chronic hepatitis B patients. J Med Virol. 2020.
Turton KL, Meier-Stephenson V, Badmalia MD, Coffin CS, Patel TR. Host transcription factors in hepatitis B Virus RNA synthesis. Viruses. 2020;12(2).
Wang J, Yu Y, Li G, Shen C, Li J, Chen S, et al. Natural history of serum HBV-RNA in chronic HBV infection. J Viral Hepat. 2018;25(9):1038–47.
Article
CAS
PubMed
Google Scholar
Wang J, Sheng Q, Ding Y, Chen R, Sun X, Chen X, et al. HBV RNA virion-like particles produced under nucleos(t)ide analogues treatment are mainly replication-deficient. J Hepatol. 2018;68(4):847–9.
Article
PubMed
Google Scholar
Gao Y, Li Y, Meng Q, Zhang Z, Zhao P, Shang Q, et al. Serum hepatitis B Virus DNA, RNA, and HBsAg: which correlated better with intrahepatic covalently closed circular DNA before and after nucleos(t)ide analogue treatment? J Clin Microbiol. 2017;55(10):2972–82.
Article
CAS
PubMed
PubMed Central
Google Scholar
Carey I, Gersch J, Wang B, Moigboi C, Kuhns M, Cloherty G, et al. Pregenomic HBV RNA and hepatitis B core-related antigen predict outcomes in hepatitis B e antigen-negative chronic hepatitis B patients suppressed on nucleos(T)ide analogue therapy. Hepatology. 2020;72(1):42–57.
Article
CAS
PubMed
Google Scholar
van Bömmel F, Bartens A, Mysickova A, Hofmann J, Krüger DH, Berg T, et al. Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors. Hepatology. 2015;61(1):66–76.
Article
PubMed
Google Scholar
Wang X, Wang Z, Chi X, Wu R, Jin Q, Xu H, et al. Efficacy of a combination of HBV RNA and HBeAg in predicting HBeAg seroconversion in patients treated with entecavir for 144 weeks. Int J Infect Dis. 2020;99:171–8.
Article
CAS
PubMed
Google Scholar
Kaewdech A, Tangkijvanich P, Sripongpun P, Witeerungrot T, Jandee S, Tanaka Y, et al. Hepatitis B surface antigen, core-related antigen and HBV RNA: predicting clinical relapse after NA therapy discontinuation. Liver Int. 2020.
Fan R, Peng J, Xie Q, Tan D, Xu M, Niu J, et al. Combining hepatitis B virus RNA and hepatitis B core-related antigen: guidance for safely stopping nucleos(t)ide analogues in hepatitis B e antigen-positive patients with chronic hepatitis B. J Infect Dis. 2020;222(4):611–8.
Article
CAS
PubMed
Google Scholar
Hadziyannis SJ, Sevastianos V, Rapti I, Vassilopoulos D, Hadziyannis E. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology. 2012;143(3):629-36.e1.
Article
CAS
PubMed
Google Scholar
Papatheodoridi M, Hadziyannis E, Berby F, Zachou K, Testoni B, Rigopoulou E, et al. Predictors of hepatitis B surface antigen loss, relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg-negative chronic hepatitis B. J Viral Hepat. 2019.
Seto WK, Liu KS, Mak LY, Cloherty G, Wong DK, Gersch J, et al. Role of serum HBV RNA and hepatitis B surface antigen levels in identifying Asian patients with chronic hepatitis B suitable for entecavir cessation. Gut. 2020.