3. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006;118:3030-3044.
4. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004;11:97-107.
8. Lopatin U. Drugs in the pipeline for HBV. Clin Liver Dis 2019;23:535-555.
9. Gane EJ. Future anti-HBV strategies. Liver Int 2017;37 Suppl 1:40-44.
11. European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370-398.
13. Drafting Committee for Hepatitis Management Guidelines and the Japan Society of Hepatology. JSH guidelines for the management of hepatitis B virus infection. Hepatol Res 2014;44 Suppl S1:1-58.
14. Velázquez RF, Rodríguez M, Navascués CA, Linares A, Pérez R, Sotorríos NG, et al. Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology 2003;37:520-527.
16. Kokudo N, Takemura N, Hasegawa K, Takayama T, Kubo S, Shimada M, et al. Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH-HCC guidelines) 2019 update. Hepatol Res 2019;49:1109-1113.
17. Lin CL, Kao JH. Perspectives and control of hepatitis B virus infection in Taiwan. J Formos Med Assoc 2015;114:901-909.
20. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130:678-686.
21. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65-73.
23. Chuaypen N, Posuwan N, Chittmittraprap S, Hirankarn N, Treeprasertsuk S, Tanaka Y, et al. Predictive role of serum HBsAg and HBcrAg kinetics in patients with HBeAg-negative chronic hepatitis B receiving pegylated interferon-based therapy. Clin Microbiol Infect 2018;24:306 e7-306.e13.
24. Brouwer WP, Chan HL, Brunetto MR, Martinot-Peignoux M, Arends P, Cornberg M, et al. Repeated measurements of hepatitis B surface antigen identify carriers of inactive HBV during long-term follow-up. Clin Gastroenterol Hepatol 2016;14:1481-1489 e5.
25. Yeo YH, Ho HJ, Yang HI, Tseng TC, Hosaka T, Trinh HN, et al. Factors associated with rates of HBsAg seroclearance in adults with chronic HBV Infection: a systematic review and meta-analysis. Gastroenterology 2019;156:635-646 e9.
26. Chen JD, Yang HI, Iloeje UH, You SL, Lu SN, Wang LY, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 2010;138:1747-1754.
27. Liu F, Wang XW, Chen L, Hu P, Ren H, Hu HD. Systematic review with meta-analysis: development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis B surface antigen seroclearance. Aliment Pharmacol Ther 2016;43:1253-1261.
28. Kim GA, Lee HC, Kim MJ, Ha Y, Park EJ, An J, et al. Incidence of hepatocellular carcinoma after HBsAg seroclearance in chronic hepatitis B patients: a need for surveillance. J Hepatol 2015;62:1092-1099.
30. Locarnini S, Zoulim F. Molecular genetics of HBV infection. Antivir Ther 2010;15 Suppl 3:3-14.
31. Kimura T, Ohno N, Terada N, Rokuhara A, Matsumoto A, Yagi S, et al. Hepatitis B virus DNA-negative dane particles lack core protein but contain a 22-kDa precore protein without C-terminal argininerich domain. J Biol Chem 2005;280:21713-21719.
33. Rokuhara A, Tanaka E, Matsumoto A, Kimura T, Yamaura T, Orii K, 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;10:324-330.
34. Maasoumy B, Wiegand SB, Jaroszewicz J, Bremer B, Lehmann P, Deterding K, et al. Hepatitis B core-related antigen (HBcrAg) levels in the natural history of hepatitis B virus infection in a large European cohort predominantly infected with genotypes A and D. Clin Microbiol Infect 2015;21:606 e1-e10.
36. Mak LY, Wong DK, Cheung KS, Seto WK, Lai CL, Yuen MF. Review article: hepatitis B core-related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection. Aliment Pharmacol Ther 2018;47:43-54.
37. Seto WK, Wong DK, Fung J, Huang FY, Liu KS, Lai CL, 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;20:1173-1180.
38. Testoni B, Lebossé F, Scholtes C, Berby F, Miaglia C, Subic M, et al. Serum hepatitis B core-related antigen (HBcrAg) correlates with covalently closed circular DNA transcriptional activity in chronic hepatitis B patients. J Hepatol 2019;70:615-625.
39. Riveiro-Barciela M, Bes M, Rodríguez-Frías F, Tabernero D, Ruiz A, Casillas R, et al. Serum hepatitis B core-related antigen is more accurate than hepatitis B surface antigen to identify inactive carriers, regardless of hepatitis B virus genotype. Clin Microbiol Infect 2017;23:860-867.
41. Hasegawa K, Nishikawa H, Enomoto H, Iwata Y, Sakai Y, Ikeda N, et al. Proposed model for the prediction of intrahepatic covalently closed circular DNA level in patients with chronic hepatitis B. Hepatol Res 2019;49:271-283.
43. 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;66:275-281.
46. Wong DK, Seto WK, Cheung KS, Chong CK, Huang FY, Fung J, et al. Hepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA. Liver Int 2017;37:995-1001.
47. Suzuki F, Miyakoshi H, Kobayashi M, Kumada H. Correlation between serum hepatitis B virus core-related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients. J Med Virol 2009;81:27-33.
49. Chuaypen N, Posuwan N, Payungporn S, Tanaka Y, Shinkai N, Poovorawan Y, 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;36:827-836.
51. Wang B, Carey I, Bruce M, Montague S, Dusheiko G, Agarwal K. HBsAg and HBcrAg as predictors of HBeAg seroconversion in HBeAg-positive patients treated with nucleos(t)ide analogues. J Viral Hepat 2018;25:886-893.
52. Wang ML, Deng R, Chen EQ, Tao CM, Liao J, Zhou TY, et al. Performance of serum HBcrAg in chronic hepatitis B patients with 8-year nucleos(t)ide analogs therapy. Clin Res Hepatol Gastroenterol 2019;43:301-309.
53. Matsumoto A, Tanaka E, Minami M, Okanoue T, Yatsuhashi H, Nagaoka S, et al. Low serum level of hepatitis B core-related antigen indicates unlikely reactivation of hepatitis after cessation of lamivudine therapy. Hepatol Res 2007;37:661-666.
54. Shinkai N, Tanaka Y, Orito E, Ito K, Ohno T, Hirashima N, et al. Measurement of hepatitis B virus core-related antigen as predicting factor for relapse after cessation of lamivudine therapy for chronic hepatitis B virus infection. Hepatol Res 2006;36:272-276.
55. Caviglia GP, Abate ML, Noviello D, Olivero A, Rosso C, Troshina G, et al. Hepatitis B core-related antigen kinetics in chronic hepatitis B virus genotype D-infected patients treated with nucleos(t)ide analogues or pegylated-interferon-α. Hepatol Res 2017;47:747-754.
57. Hsu YC, Nguyen MH, Mo LR, Wu MS, Yang TH, Chen CC, et al. Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk. Aliment Pharmacol Ther 2019;49:107-115.
59. Ando Y, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Hayashi K, et al. Cumulative incidence and risk factors for the development of hepatocellular carcinoma in patients with chronic hepatitis B who achieved sustained disappearance of viremia by nucleos(t)ide analog treatment. Hepatol Res 2018;48:E240-E251.
61. Hosaka T, Suzuki F, Kobayashi M, Fujiyama S, Kawamura Y, Sezaki H, et al. Impact of hepatitis B core-related antigen on the incidence of hepatocellular carcinoma in patients treated with nucleos(t)ide analogues. Aliment Pharmacol Ther 2019;49:457-471.
62. Kumada T, Toyoda H, Tada T, Kiriyama S, Tanikawa M, Hisanaga Y, et al. Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic hepatitis B patients: a propensity score analysis. J Hepatol 2013;58:427-433.
63. Honda M, Shirasaki T, Terashima T, Kawaguchi K, Nakamura M, Oishi N, 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;213:1096-1106.
64. Tada T, Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, et al. HBcrAg predicts hepatocellular carcinoma development: an analysis using time-dependent receiver operating characteristics. J Hepatol 2016;65:48-56.
65. Tseng TC, Liu CJ, Hsu CY, Hong CM, Su TH, Yang WT, et al. High level of hepatitis B core-related antigen associated with increased risk of hepatocellular carcinoma in patients with chronic HBV infection of intermediate viral load. Gastroenterology 2019;157:1518-1529 e3.
66. Cheung KS, Seto WK, Wong DK, Lai CL, Yuen MF. Relationship between HBsAg, HBcrAg and hepatocellular carcinoma in patients with undetectable HBV DNA under nucleos(t)ide therapy. J Viral Hepat 2017;24:654-661.
67. Suzuki Y, Maekawa S, Komatsu N, Sato M, Tatsumi A, Miura M, et al. Hepatitis B virus (HBV)-infected patients with low hepatitis B surface antigen and high hepatitis B core-related antigen titers have a high risk of HBV-related hepatocellular carcinoma. Hepatol Res 2019;49:51-63.
68. Chen S, Jia J, Gao Y, Li H, Fang M, Feng H, et al. Clinical evaluation of hepatitis B core-related antigen in chronic hepatitis B and hepatocellular carcinoma patients. Clin Chim Acta 2018;486:237-244.
70. Narimatsu H. Development of M2BPGi: a novel fibrosis serum glyco-biomarker for chronic hepatitis/cirrhosis diagnostics. Expert Rev Proteomics 2015;12:683-693.
73. Zou X, Zhu MY, Yu DM, Li W, Zhang DH, Lu FJ, et al. Serum WFA+-M2BP levels for evaluation of early stages of liver fibrosis in patients with chronic hepatitis B virus infection. Liver Int 2017;37:35-44.
77. Chuaypen N, Chittmittraprap S, Pinjaroen N, Sirichindakul B, Poovorawan Y, Tanaka Y, et al. Serum Wisteria floribunda agglutininpositive Mac-2 binding protein level as a diagnostic marker of hepatitis B virus-related hepatocellular carcinoma. Hepatol Res 2018;48:872-881.
78. Kim SU, Heo JY, Kim BK, Park JY, Kim DY, Han KH, et al. Wisteria floribunda agglutinin-positive human Mac-2 binding protein predicts the risk of HBV-related liver cancer development. Liver Int 2017;37:879-887.
79. Kawanaka M, Tomiyama Y, Hyogo H, Koda M, Shima T, Tobita H, et al. Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts the development of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease. Hepatol Res 2018;48:521-528.
80. Yasui Y, Kurosaki M, Komiyama Y, Takada H, Tamaki N, Watakabe K, et al. Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts early occurrence of hepatocellular carcinoma after sustained virologic response by direct-acting antivirals for hepatitis C virus. Hepatol Res 2018;48:1131-1139.
83. Hsu YC, Jun T, Huang YT, Yeh ML, Lee CL, Ogawa S, et al. Serum M2BPGi level and risk of hepatocellular carcinoma after oral antiviral therapy in patients with chronic hepatitis B. Aliment Pharmacol Ther 2018;48:1128-1137.
89. Heimbach JK. Overview of the updated AASLD guidelines for the management of HCC. Gastroenterol Hepatol (N Y) 2017;13:751-753.
90. Aghemo A. Update on HCC management and review of the new EASL guidelines. Gastroenterol Hepatol (N Y) 2018;14:384-386.
92. Fedi P, Bafico A, Nieto Soria A, Burgess WH, Miki T, Bottaro DP, et al. Isolation and biochemical characterization of the human Dkk1 homologue, a novel inhibitor of mammalian Wnt signaling. J Biol Chem 1999;274:19465-19472.
94. Wang J, Xu Y, Zhao H, Zhang X. Change of circulating antibodies against CD25-derived peptide antigen in hepatocellular carcinoma. J Cancer Res Ther 2017;13:813-816.
96. Tatarinov IuS. Detection of embryo-specific alpha-globulin in the blood serum of a patient with primary liver cancer. Vopr Med Khim 1964;10:90-91.
102. Sterling RK, Jeffers L, Gordon F, Venook AP, Reddy KR, Satomura S, et al. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol 2009;7:104-113.
105. Li D, Mallory T, Satomura S. AFP-L3: a new generation of tumor marker for hepatocellular carcinoma. Clin Chim Acta 2001;313:15-19.
106. Choi J, Kim GA, Han S, Lee W, Chun S, Lim YS. Longitudinal assessment of three serum biomarkers to detect very early-stage hepatocellular carcinoma. Hepatology 2019;69:1983-1994.
107. Toyoda H, Kumada T, Tada T. Highly sensitive Lens culinaris agglutinin-reactive α-fetoprotein: a new tool for the management of hepatocellular carcinoma. Oncology 2011;81 Suppl 1:61-65.
108. Kobayashi M, Hosaka T, Ikeda K, Seko Y, Kawamura Y, Sezaki H, et al. Highly sensitive AFP-L3% assay is useful for predicting recurrence of hepatocellular carcinoma after curative treatment preand postoperatively. Hepatol Res 2011;41:1036-1045.
111. Naraki T, Kohno N, Saito H, Fujimoto Y, Ohhira M, Morita T, et al. Gamma-carboxyglutamic acid content of hepatocellular carcinoma-associated des-gamma-carboxy prothrombin. Biochim Biophys Acta 2002;1586:287-298.
112. Pote N, Cauchy F, Albuquerque M, Voitot H, Belghiti J, Castera L, et al. Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion. J Hepatol 2015;62:848-854.
114. Koike Y, Shiratori Y, Sato S, Obi S, Teratani T, Imamura M, et al. Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer 2001;91:561-569.
116. Lee S, Rhim H, Kim YS, Kang TW, Song KD. Post-ablation desgamma-carboxy prothrombin level predicts prognosis in hepatitis B-related hepatocellular carcinoma. Liver Int 2016;36:580-587.
119. Caviglia GP, Ribaldone DG, Abate ML, Ciancio A, Pellicano R, Smedile A, et al. Performance of protein induced by vitamin K absence or antagonist-II assessed by chemiluminescence enzyme immunoassay for hepatocellular carcinoma detection: a metaanalysis. Scand J Gastroenterol 2018;53:734-740.
122. Caviglia GP, Abate ML, Gaia S, Petrini E, Bosco C, Olivero A, et al. Risk of hepatocellular carcinoma in HBV cirrhotic patients assessed by the combination of miR-122, AFP and PIVKA-II. Panminerva Med 2017;59:283-289.
123. Sassa T, Kumada T, Nakano S, Uematsu T. Clinical utility of simultaneous measurement of serum high-sensitivity des-gammacarboxy prothrombin and Lens culinaris agglutinin A-reactive alpha-fetoprotein in patients with small hepatocellular carcinoma. Eur J Gastroenterol Hepatol 1999;11:1387-1392.
124. Erdal H, Gül Utku Ö, Karatay E, Çelik B, Elbeg Ş, Doğan İ. Combination of DKK1 and AFP improves diagnostic accuracy of hepatocellular carcinoma compared with either marker alone. Turk J Gastroenterol 2016;27:375-381.
126. Shen Q, Fan J, Yang XR, Tan Y, Zhao W, Xu Y, et al. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol 2012;13:817-826.
127. Fouad YM, Mohamed HI, Kamal EM, Rasek MA. Clinical significance and diagnostic value of serum dickkopf-1 in patients with hepatocellular carcinoma. Scand J Gastroenterol 2016;51:1133-1137.
128. Sakabe T, Azumi J, Umekita Y, Toriguchi K, Hatano E, Hirooka Y, et al. Expression of cancer stem cell-associated DKK1 mRNA serves as prognostic marker for hepatocellular carcinoma. Anticancer Res 2017;37:4881-4888.
133. Nishikawa H, Enomoto H, Iwata Y, Kishino K, Shimono Y, Hasegawa K, et al. Serum Wisteria floribunda agglutinin-positive Mac2-binding protein for patients with chronic hepatitis B and C: a comparative study. J Viral Hepat 2016;23:977-984.
134. Ichikawa Y, Joshita S, Umemura T, Shobugawa Y, Usami Y, Shibata S, et al. Serum Wisteria floribunda agglutinin-positive human Mac2 binding protein may predict liver fibrosis and progression to hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Hepatol Res 2017;47:226-233.
138. Nguyen MH, Garcia RT, Simpson PW, Wright TL, Keeffe EB. Racial differences in effectiveness of alpha-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis. Hepatology 2002;36:410-417.
139. inoue t, tanaka y. today’s new laboratory tests-how to select and use (3). liver disease weekly japan medical news 2015;4771:40-45.
140. Matsumoto A, Yatsuhashi H, Nagaoka S, Suzuki Y, Hosaka T, Tsuge M, et al. Factors associated with the effect of interferon-α sequential therapy in order to discontinue nucleoside/nucleotide analog treatment in patients with chronic hepatitis B. Hepatol Res 2015;45:1195-1202.
141. Tanaka E, Matsumoto A, Suzuki F, Kobayashi M, Mizokami M, Tanaka Y, et al. Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance. Liver Int 2006;26:90-96.