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Review

Biomarkers for hepatitis B virus replication: an overview and a look to the future

, & ORCID Icon
Pages 1131-1139 | Received 09 May 2020, Accepted 24 Aug 2020, Published online: 17 Sep 2020

References

  • Polaris Observatory C. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018 Jun 3;6:383–403. PubMed PMID: 29599078.
  • Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016 Jan;63(1):261–283. PubMed PMID: 26566064; PubMed Central PMCID: PMCPMC5987259.
  • European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370–398. PubMed PMID: 28427875.
  • Lucifora J, Protzer U. Attacking hepatitis B virus cccDNA–The holy grail to hepatitis B cure. J Hepatol. 2016 Apr;64(1Suppl):S41–S48. PubMed PMID: 27084036.
  • Charre C, Levrero M, Zoulim F, et al. Non-invasive biomarkers for chronic hepatitis B virus infection management. Antiviral Res. 2019 Sep;169:104553. PubMed PMID: 31288041.
  • Lin CL, Kao JH. New perspectives of biomarkers for the management of chronic hepatitis B. Clin Mol Hepatol. 2016 Dec;22(4):423–431. PubMed PMID: 28081591; PubMed Central PMCID: PMCPMC5266347.
  • Yuen MF, Chen DS, Dusheiko GM, et al. Hepatitis B virus infection. Nat Rev Dis Primers. 2018 Jun;7;4:18035. PubMed PMID: 29877316.
  • Urban S, Schulze A, Dandri M, et al. The replication cycle of hepatitis B virus. J Hepatol. 2010 Feb;52(2):282–284. PubMed PMID: 20056291.
  • Yang HC, Chen PJ. The potential and challenges of CRISPR-Cas in eradication of hepatitis B virus covalently closed circular DNA. Virus Res. 2018 Jan 15;244:304–310. PubMed PMID: 28627393.
  • Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015 Dec;64(12):1972–1984. PubMed PMID: 26048673.
  • Tong S, Revill P. Overview of hepatitis B viral replication and genetic variability. J Hepatol. 2016 Apr;64(1Suppl):S4–S16. PubMed PMID: 27084035; PubMed Central PMCID: PMCPMC4834849.
  • Cornberg M, Wong VW, Locarnini S, et al. The role of quantitative hepatitis B surface antigen revisited. J Hepatol. 2017 Feb;66(2):398–411. PubMed PMID: 27575311.
  • Chan HL, Wong VW, Wong GL, et al. A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B.. Hepatology. 2010 Oct;52(4):1232–1241. PubMed PMID: 20648555.
  • Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. J Hepatol. 2010 Apr;52(4):508–513. PubMed PMID: 20206400.
  • Thompson AJ, Nguyen T, Iser D, et al. Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology. 2010 Jun;51(6):1933–1944. PubMed PMID: 20512987.
  • Seto WK, Wong DK, Fung J, et al. High hepatitis B surface antigen levels predict insignificant fibrosis in hepatitis B e antigen positive chronic hepatitis B. PLoS One. 2012;7(8):e43087. PubMed PMID: 22916211; PubMed Central PMCID: PMCPMC3423440.
  • Martinot-Peignoux M, Carvalho-Filho R, Lapalus M, et al. Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naive, e antigen-positive patients. J Hepatol. 2013 Jun;58(6):1089–1095. PubMed PMID: 23369792.
  • Yang Y, Gao J, Tan YT, et al. Individual and combined effects of hepatitis B surface antigen level and viral load on liver cancer risk. J Gastroenterol Hepatol. 2018 May;33(5):1131–1137. PubMed PMID: 29065440; PubMed Central PMCID: PMCPMC5902426.
  • Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65–73. PubMed PMID: 16391218.
  • Yip TC, Chan HL, Wong VW, et al. Impact of age and gender on risk of hepatocellular carcinoma after hepatitis B surface antigen seroclearance. J Hepatol. 2017 Nov;67(5):902–908. PubMed PMID: 28652084.
  • Yip TC, Wong GL, Chan HL, et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019 Mar;70(3):361–370. PubMed PMID: 30367899.
  • Liu F, Wang XW, Chen L, et al. Systematic review with meta-analysis: development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis B surface antigen seroclearance. Aliment Pharmacol Ther. 2016 Jun;43(12):1253–1261. PubMed PMID: 27117732.
  • Moucari R, Mackiewicz V, Lada O, et al. Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology. 2009 Apr;49(4):1151–1157. PubMed PMID: 19115222.
  • Wursthorn K, Jung M, Riva A, et al. Kinetics of hepatitis B surface antigen decline during 3 years of telbivudine treatment in hepatitis B e antigen-positive patients. Hepatology. 2010 Nov;52(5):1611–1620. PubMed PMID: 20931556.
  • Seto WK, Wong DK, Fung J, et al. Reduction of hepatitis B surface antigen levels and hepatitis B surface antigen seroclearance in chronic hepatitis B patients receiving 10 years of nucleoside analogue therapy. Hepatology. 2013 Sep;58(3):923–931. PubMed PMID: 23468172.
  • Sonneveld MJ, Hansen BE, Piratvisuth T, et al. Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levels. Hepatology. 2013 Sep;58(3):872–880. PubMed PMID: 23553752.
  • Marcellin P, Bonino F, Yurdaydin C, et al. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int. 2013 Mar 7;(1):88–97. PubMed PMID: 23518903; PubMed Central PMCID: PMCPMC3601258. DOI:10.1007/s12072-012-9343-x
  • Pavlovic V, Yang L, Chan HL, et al. Peginterferon alfa-2a (40 kD) stopping rules in chronic hepatitis B: a systematic review and meta-analysis of individual participant data. Antivir Ther. 2019;24(2):133–140. PubMed PMID: 30865588.
  • Wang CC, Tseng KC, Hsieh TY, et al. Assessing the durability of entecavir-treated Hepatitis B using quantitative HBsAg. Am J Gastroenterol. 2016 Sep;111(9):1286–1294. PubMed PMID: 27045923.
  • Qiu YW, Huang LH, Yang WL, et al. Hepatitis B surface antigen quantification at hepatitis B e antigen seroconversion predicts virological relapse after the cessation of entecavir treatment in hepatitis B e antigen-positive patients. Int J Infect Dis. 2016 Feb;43:43–48. PubMed PMID: 26523639.
  • Hosaka T, Suzuki F, Kobayashi M, et al. Clearance of hepatitis B surface antigen during long-term nucleot(s)ide analog treatment in chronic hepatitis B: results from a nine-year longitudinal study. J Gastroenterol. 2013 Aug;48(8):930–941. PubMed PMID: 23065021.
  • Hadziyannis E, Laras A. Viral Biomarkers in Chronic HBeAg Negative HBV Infection. Genes (Basel). 2018 Sep 27;9(10). PubMed PMID: 30262738; PubMed Central PMCID: PMCPMC6210948. DOI:10.3390/genes9100469
  • Broquetas T, Garcia-Retortillo M, Hernandez JJ, et al. Quantification of HBsAg to predict low levels and seroclearance in HBeAg-negative patients receiving nucleos(t)ide analogues. PLoS One. 2017;12(11):e0188303. PubMed PMID: 29190670; PubMed Central PMCID: PMCPMC5708657.
  • Rokuhara A, Tanaka E, Matsumoto A, et al. Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core-related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment. J Viral Hepat. 2003 Jul;10(4):324–330. PubMed PMID: 12823601.
  • Chen EQ, Feng S, Wang ML, et al. Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B. Sci Rep. 2017 Mar 14;7(1):173. PubMed PMID: 28282964; PubMed Central PMCID: PMCPMC5427896.
  • Chen EQ, Wang ML, Tao YC, et al. Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA. J Viral Hepat. 2019 May;26(5):586–595. PubMed PMID: 30632235.
  • Wang ML, Liao J, Wei B, et al. Comparison of hepatitis B virus core-related antigen and hepatitis B surface antigen for predicting HBeAg seroconversion in chronic hepatitis B patients with pegylated interferon therapy. Infect Dis (Lond). 2018 Jul;50(7):522–530. PubMed PMID: 29463147.
  • Chuaypen N, Posuwan N, Payungporn S, et al. Serum hepatitis B core-related antigen as a treatment predictor of pegylated interferon in patients with HBeAg-positive chronic hepatitis B. Liver Int. 2016 Jun;36(6):827–836. PubMed PMID: 26678018.
  • Song G, Yang R, Rao H, et al. Serum HBV core-related antigen is a good predictor for spontaneous HBeAg seroconversion in chronic hepatitis B patients. J Med Virol. 2017 Mar;89(3):463–468. PubMed PMID: 27505145.
  • Seto WK, Wong DK, Fung J, et al. Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B. Clin Microbiol Infect. 2014 Nov;20(11):1173–1180. PubMed PMID: 24975365.
  • Drafting Committee for Hepatitis Management G, the Japan Society of H. JSH guidelines for the management of Hepatitis B virus infection. Hepatol Res. 2014 Jan;44(Suppl S1):1–58. PubMed PMID: 24397839.
  • Wang ML, Chen EQ, Tao CM, et al. Pronounced decline of serum HBsAg in chronic hepatitis B patients with long-term effective nucleos(t)ide analogs therapy. Scand J Gastroenterol. 2017 Dec;52(12):1420–1426. PubMed PMID: 28880694.
  • Wang ML, Deng R, Chen EQ, et al. Performance of serum HBcrAg in chronic hepatitis B patients with 8-year nucleos(t)ide analogs therapy. Clin Res Hepatol Gastroenterol. 2019 Jun;43(3):301–309. PubMed PMID: 30497844.
  • Honda M, Shirasaki T, Terashima T, et al. Hepatitis B Virus (HBV) core-related antigen during Nucleos(t)ide analog therapy is related to intra-hepatic HBV replication and development of hepatocellular carcinoma. J Infect Dis. 2016 Apr 1;213(7):1096–1106. PubMed PMID: 26621908.
  • Tada T, Kumada T, Toyoda H, et al. HBcrAg predicts hepatocellular carcinoma development: an analysis using time-dependent receiver operating characteristics. J Hepatol. 2016 Jul;65(1):48–56. PubMed PMID: 27034253.
  • Cheung KS, Seto WK, Wong DK, et al. Relationship between HBsAg, HBcrAg and hepatocellular carcinoma in patients with undetectable HBV DNA under nucleos(t)ide therapy. J Viral Hepat. 2017 Aug;24(8):654–661. PubMed PMID: 28185363.
  • Kock J, Theilmann L, Galle P, et al. Hepatitis B virus nucleic acids associated with human peripheral blood mononuclear cells do not originate from replicating virus. Hepatology. 1996 Mar;23(3):405–413. PubMed PMID: 8617418.
  • Butler EK, Gersch J, McNamara A, 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 Dec;68(6):2106–2117. PubMed PMID: 29734472.
  • Huang H, Wang J, Li W, et al. Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naive HBV-infected individuals. J Clin Virol. 2018 Feb–Mar;99–100:71–78. PubMed PMID: 29353073.
  • Wang J, Yu Y, Li G, et al. Natural history of serum HBV-RNA in chronic HBV infection. J Viral Hepat. 2018 Sep;25(9):1038–1047. PubMed PMID: 29633430.
  • van Campenhout MJH, van Bommel F, Pfefferkorn M, et al. Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment. Hepatology. 2018 Sep;68(3):839–847. PubMed PMID: 29514389; PubMed Central PMCID: PMCPMC6175227.
  • Wang J, Shen T, Huang X, 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 Oct;65(4):700–710. PubMed PMID: 27245431.
  • Bai F, Yano Y, Fukumoto T, et al. Quantification of pregenomic RNA and covalently closed circular DNA in hepatitis B virus-related hepatocellular carcinoma. Int J Hepatol. 2013;2013:849290. PubMed PMID: 24455286; PubMed Central PMCID: PMCPMC3880697.
  • van Bommel F, Bartens A, Mysickova A, 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 Jan;61(1):66–76. PubMed PMID: 25132147.
  • Huang YW, Chayama K, Kao JH, et al. Detectability and clinical significance of serum hepatitis B virus ribonucleic acid. Hepatobiliary Surg Nutr. 2015 Jun 4;(3):197–202. PubMed PMID: 26151059; PubMed Central PMCID: PMCPMC4465601. DOI:10.3978/j.2304-3881.2014.11.08
  • Huang YW, Takahashi S, Tsuge M, et al. On-treatment low serum HBV RNA level predicts initial virological response in chronic hepatitis B patients receiving nucleoside analogue therapy. Antivir Ther. 2015;20(4):369–375. PubMed PMID: 24739420.
  • Song LW, Liu PG, Liu CJ, et al. Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection. Clin Microbiol Infect. 2015 Feb;21(2):197–203. PubMed PMID: 25658546.
  • Xu JH, Song LW, Li N, et al. Baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long-term entecavir. J Viral Hepat. 2017 Feb;24(2):148–154. PubMed PMID: 27891715.
  • Kumar M, Sarin SK, Hissar S, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology. 2008 May;134(5):1376–1384. PubMed PMID: 18471514.
  • Zhou J, Song L, Zhao H, et al. Serum hepatitis B core antibody as a biomarker of hepatic inflammation in chronic hepatitis B patients with normal alanine aminotransferase. Sci Rep. 2017 Jun 5;7(1):2747. PubMed PMID: 28584279; PubMed Central PMCID: PMCPMC5459818.
  • Liu XJ, Zhang F, Liu Y, et al. Effects of total nocturnal sleep time and siesta on hepatocellular carcinoma risks in individuals with chronic HBV infection. Sleep Biol Rhythms. 2018 Jan;16(1):99–105. PubMed PMID: WOS:000425888800012.
  • Yuan Q, Song LW, Liu CJ, et al. Quantitative hepatitis B core antibody level may help predict treatment response in chronic hepatitis B patients. Gut. 2013 Jan;62(1):182–184. PubMed PMID: 22698651.
  • Fan R, Sun J, Yuan Q, et al. Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues. Gut. 2016 Feb;65(2):313–320. PubMed PMID: 25586058; PubMed Central PMCID: PMCPMC4752655.
  • Chi H, Li Z, Hansen BE, et al. Serum level of antibodies against Hepatitis B core protein is associated with clinical relapse after discontinuation of Nucleos(t)ide analogue therapy. Clin Gastroenterol Hepatol. 2019 Jan;17(1):182–191e1. PubMed PMID: 29902645.
  • Bozza C, Cinausero M, Iacono D, et al. Hepatitis B and cancer: A practical guide for the oncologist. Crit Rev Oncol Hematol. 2016 Feb;98:137–146. PubMed PMID: 26657667.
  • Huang YH, Hsiao LT, Hong YC, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol. 2013 Aug 1;31(22):2765–2772. PubMed PMID: 23775967.
  • Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic Hepatitis B: AASLD 2018 Hepatitis B guidance. Clin Liver Dis. 2018 Jul;12(1):33–34. PubMed PMID: 30988907; PubMed Central PMCID: PMCPMC6385899..
  • Yang C, Qin B, Yuan Z, et al. Meta-analysis of prophylactic entecavir or lamivudine against hepatitis B virus reactivation. Ann Hepatol. 2016 Jul-Aug;15(4):501–511. PubMed PMID: 27236149.
  • Zhang MY, Zhu GQ, Shi KQ, et al. Systematic review with network meta-analysis: comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation. Oncotarget. 2016 May 24;7(21):30642–30658. PubMed PMID: 27121321; PubMed Central PMCID: PMCPMC5058707.
  • Yang HC, Tsou HH, Pei SN, et al. Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection. J Hepatol. 2018 Aug;69(2):286–292. PubMed PMID: 29551710.
  • Hou JL, Zhao W, Lee C, et al. Outcomes of long-term treatment of chronic HBV infection with entecavir or other agents from a randomized trial in 24 countries. Clin Gastroenterol Hepatol. 2020 Feb;18(2):457–467e21. PubMed PMID: 31306800.
  • Kim JH, Sinn DH, Kang W, et al. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment. Hepatology. 2017 Aug;66(2):335–343. PubMed PMID: 28012257.
  • Weber J, Sahoo MK, Taylor N, et al. Comparison of transcription-mediated amplification and real-time PCR assays for Hepatitis B Virus DNA quantitation in serum. J Appl Lab Med. 2019 Nov 4;(3):383–390. PubMed PMID: 31659075. DOI:10.1373/jalm.2019.029058
  • Schalasta G, Borner A, Speicher A, et al. Evaluation of the Aptima HBV Quant assay vs. the COBAS TaqMan HBV test using the high pure system for the quantitation of HBV DNA in plasma and serum samples. Clin Chem Lab Med. 2018 Mar 28;56(4):634–641. PubMed PMID: 29197859.
  • Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678–686. PubMed PMID: 16530509.
  • Lin CL, Kao JH. Hepatitis B viral factors and treatment responses in chronic hepatitis B. J Formos Med Assoc. 2013 Jun;112(6):302–311. PubMed PMID: 23787007.
  • Chinese Society of Infectious Diseases CMA, Chinese Society of Hepatology CMA. The guidelines of prevention and treatment for chronic hepatitis B (2019 version). Zhonghua Gan Zang Bing Za Zhi. 2019 Dec 20;27(12):938–961. PubMed PMID: 31941257.
  • Liaw YF, Kao JH, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012 Jun 6;(3):531–561. PubMed PMID: 26201469. DOI:10.1007/s12072-012-9365-4
  • European Association For The Study Of The L. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012 Jul;57(1):167–185. PubMed PMID: 22436845.
  • Smolders EJ, Burger DM, Feld JJ, et al. Review article: clinical pharmacology of current and investigational hepatitis B virus therapies. Aliment Pharmacol Ther. 2020 Jan;51(2):231–243. PubMed PMID: 31840863.
  • Durantel D, Zoulim F. New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus. J Hepatol. 2016 Apr;64(1Suppl):S117–S131. PubMed PMID: 27084032.
  • Paulsen D, Weber O, Ruebsamen-Schaeff H, et al. AIC649 induces a bi-phasic treatment response in the woodchuck model of chronic Hepatitis B.. PLoS One. 2015;10(12):e0144383. PubMed PMID: 26656974; PubMed Central PMCID: PMCPMC4690600.
  • Li N, Feng L, Han HQ, et al. A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis. Cancer Lett. 2016 Oct 10;381(1):14–22. PubMed PMID: 27424523.
  • Pan JL, Xu XY. Research progress of siRNA in reducing serum HBsAg levels in patients with chronic hepatitis B. Zhonghua Gan Zang Bing Za Zhi. 2020 Feb 20;28(2):179–182. PubMed PMID: 32164074.
  • Blank A, Markert C, Hohmann N, et al. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016 Sep;65(3):483–489. PubMed PMID: 27132172.
  • Javitt NB. Blocking sodum-taurocholate cotransporting polypeptide stimulates biliary cholesterol and phospholipid secretion in mice. Hepatology. 2020 May 4. PubMed PMID: 32367585. DOI:10.1002/hep.31292
  • Volz T, Allweiss L, Ben MM, et al. The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. J Hepatol. 2013 May;58(5):861–867. PubMed PMID: 23246506.
  • Phyo WW, Soh AY, Lim SG, et al. Search for a cure for chronic hepatitis B infection: how close are we? World J Hepatol. 2015 May 28;7(9):1272–1281. PubMed PMID: 26019743; PubMed Central PMCID: PMCPMC4438502.
  • Sun FK, Sun Q, Fan YC, et al. Methylation of tissue factor pathway inhibitor 2 as a prognostic biomarker for hepatocellular carcinoma after hepatectomy. J Gastroenterol Hepatol. 2016 Feb;31(2):484–492. PubMed PMID: WOS:000369398400030.
  • Brouwer WP, Chan HL, Brunetto MR, et al. Repeated measurements of Hepatitis B surface antigen identify carriers of inactive HBV during long-term follow-up. Clin Gastroenterol Hepatol. 2016 Oct;14(10):1481–1489e5. PubMed PMID: 26872398.
  • Luo J, Cui X, Gao L, et al. Identification of an intermediate in Hepatitis B Virus Covalently Closed Circular (CCC) DNA formation and sensitive and selective CCC DNA detection. J Virol. 2017 Sep 1;91(17). PubMed PMID: 28637752; PubMed Central PMCID: PMCPMC5553186. DOI:10.1128/JVI.00539-17
  • Jiang PX, Mao RC, Dong MH, et al. Exonuclease I and III improve the detection efficacy of hepatitis B virus covalently closed circular DNA. Hepatobiliary Pancreat Dis Int. 2019 Oct;18(5):458–463. PubMed PMID: 30522829.
  • Caviglia GP, Abate ML, Tandoi F, et al. Quantitation of HBV cccDNA in anti-HBc-positive liver donors by droplet digital PCR: a new tool to detect occult infection. J Hepatol. 2018 Aug;69(2):301–307. PubMed PMID: 29621551.

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