Hepatitis B core-related antigen levels after HBeAg seroconversion is associated with the development of hepatocellular carcinoma.
Adult
Biomarkers
Carcinoma, Hepatocellular
/ blood
Disease Susceptibility
Female
Hepatitis B Core Antigens
/ blood
Hepatitis B e Antigens
/ blood
Hepatitis B virus
/ immunology
Hepatitis B, Chronic
/ complications
Humans
Incidence
Liver Neoplasms
/ blood
Male
Middle Aged
Proportional Hazards Models
ROC Curve
Risk Factors
Seroconversion
chronic hepatitis B
cirrhosis
hepatitis B core-related antigen
hepatocellular carcinoma
Journal
Journal of viral hepatitis
ISSN: 1365-2893
Titre abrégé: J Viral Hepat
Pays: England
ID NLM: 9435672
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
18
12
2018
revised:
03
06
2019
accepted:
18
07
2019
pubmed:
17
8
2019
medline:
21
7
2020
entrez:
17
8
2019
Statut:
ppublish
Résumé
Hepatitis B core-related antigen (HBcrAg) is a novel serological marker for hepatitis B virus infection. Its clinical significance after HBeAg seroconversion has not been defined. We aimed to determine the relationship between HBcrAg levels after spontaneous HBeAg seroconversion and hepatocellular carcinoma (HCC). A total of 207 chronic hepatitis B patients with documented time of HBeAg seroconversion were enrolled. HBcrAg and HBsAg were checked within 3 years (as baseline), at 5 and 10 years after HBeAg seroconversion. HBV DNA was measured at the baseline. Multivariate Cox regression model was used to investigate the predictors for HCC development. The median follow-up time was 13.1 (11.8-15.5) years. Fourteen patients developed HCC (15-year cumulative incidence: 7%). The median level of HBcrAg at baseline was significantly higher in patients who developed HCC when compared with patients without HCC (5.68 vs 4.78 log U/ml, respectively; P = .003). Cox proportional hazards model indicated that age of HBeAg seroconversion older than 40 years (hazard ratio (HR): 4.60; P = .049), presence of baseline cirrhosis (HR: 6.23; P = .003) and a higher baseline HBcrAg (HR: 1.75; P = .032) were independently associated with HCC development. A cut-off value of baseline HBcrAg level ≥5.21 log U/mL yielded an AUROC of 0.74 with a negative predictive value of 97.7%. High HBcrAg levels within 3 years after HBeAg seroconversion were independently associated with the development of HCC in chronic hepatitis B patients.
Substances chimiques
Biomarkers
0
Hepatitis B Core Antigens
0
Hepatitis B e Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1473-1480Informations de copyright
© 2019 John Wiley & Sons Ltd.
Références
WHO. World Health Organization factsheets for chronic hepatitis B (last updated July 2017). Assessed February 20, 2018. Available at: http://www.who.int/mediacentre/factsheets/fs204/en.
Liaw YF, Tai DI, Chu CM, et al. Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. A prospective study. Gastroenterology. 1986;90(2):263-267.
Sherman M, Peltekian KM, Lee C. Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology. 1995;22(2):432-438.
Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer. 1988;61(10):1942-1956.
Yuen MF, Tanaka Y, Fong DY, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol. 2009;50(1):80-88.
Yang HI, Yuen MF, Chan HL, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol. 2011;12(6):568-574.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118-1127.
Yuen MF, Tanaka Y, Mizokami M, et al. Role of hepatitis B virus genotypes Ba and C, core promoter and precore mutations on hepatocellular carcinoma: a case control study. Carcinogenesis. 2004;25(9):1593-1598.
Liu S, Zhang H, Gu C, et al. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst. 2009;101(15):1066-1082.
Yeung P, Wong DK, Lai CL, Fung J, Seto WK, Yuen MF. Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B. J Infect Dis. 2011;203(5):646-654.
Yuen MF, Tanaka Y, Shinkai N, et al. Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels. Gut. 2008;57(1):98-102.
Yuen MF, Wong DK, Fung J, et al. HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology. 2008;135(4):1192-1199.
Tseng TC, Liu CJ, Yang HC, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology. 2012;142(5):1140-1149. e1143; quiz e1113-1144.
Chen JD, Yang HI, Iloeje UH, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology. 2010;138(5):1747-1754.
Kim GA, Lee HC, Kim MJ, et al. Incidence of hepatocellular carcinoma after HBsAg seroclearance in chronic hepatitis B patients: a need for surveillance. J Hepatol. 2015;62(5):1092-1099.
Wong DK, Tanaka Y, Lai CL, Mizokami M, Fung J, Yuen MF. Hepatitis B virus core-related antigens as markers for monitoring chronic hepatitis B infection. J Clin Microbiol. 2007;45(12):3942-3947.
Wong DK, Seto WK, Cheung KS, et al. Hepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA. Liver Int. 2017;37(7):995-1001.
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;20(11):1173-1180.
Shinkai N, Tanaka Y, Orito E, 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(4):272-276.
Jung KS, Park JY, Chon YE, et al. Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients. J Gastroenterol. 2016;51(8):830-839.
Tada T, Kumada T, Toyoda H, et al. HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics. J Hepatol. 2016;65(1):48-56.
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(8):654-661.
Hosaka T, Suzuki F, Kobayashi M, et al. HBcrAg is a predictor of post-treatment recurrence of hepatocellular carcinoma during antiviral therapy. Liver Int. 2010;30(10):1461-1470.
Chen YC, Chu CM, Liaw YF. Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology. 2010;51(2):435-444.
Kumada T, Toyoda H, Tada T, et al. Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic hepatitis B patients: a propensity score analysis. J Hepatol. 2013;58(3):427-433.
Tada T, Kumada T, Toyoda H, Kobayashi N, Akita T, Tanaka J. Hepatitis B virus core-related antigen levels predict progression to liver cirrhosis in hepatitis B carriers. J Gastroenterol Hepatol. 2018;33(4):918-925.