Premium
Impact of hepatitis B core‐related antigen on the incidence of hepatocellular carcinoma in patients treated with nucleos(t)ide analogues
Author(s) -
Hosaka Tetsuya,
Suzuki Fumitaka,
Kobayashi Masahiro,
Fujiyama Shunichirou,
Kawamura Yusuke,
Sezaki Hitomi,
Akuta Norio,
Suzuki Yoshiyuki,
Saitoh Satoshi,
Arase Yasuji,
Ikeda Kenji,
Kobayashi Mariko,
Kumada Hiromitsu
Publication year - 2019
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.15108
Subject(s) - medicine , hepatocellular carcinoma , hazard ratio , gastroenterology , cohort , hepatitis b virus , hepatitis b , incidence (geometry) , antigen , confidence interval , proportional hazards model , immunology , virus , physics , optics
Summary Background Chronic hepatitis B virus ( HBV ) infection is an aetiologic factor for hepatocellular carcinoma ( HCC ). Baseline HBV DNA is a known independent predictor of HCC , and the serum hepatitis B core‐related antigen ( HB crAg) level corresponds to intrahepatic covalently closed circular DNA . Aim To investigate whether the baseline and on‐treatment serum HB crAg levels can predict HCC incidence in patients with chronic hepatitis B following nucleos(t)ide analogue ( NA ) therapy. Methods This retrospective cohort study included 1268 patients treated with NA s for >1 year. In all patients, serum HB crAg and hepatitis B surface antigen levels were measured at baseline and 1 year. Results During a median follow‐up of 8.9 years, 113 patients (8.9%) developed HCC (10.3/1000 person‐years). These patients were stratified by baseline hepatitis B e‐antigen ( HB eAg) status into HB eAg+ and HB eAg‐ cohorts. High on‐treatment HB crAg levels at 1 year were found to associate significantly with HCC ( HB eAg+ cohort: P = 0.017; HB eAg‐ cohort: P = 4.30 × 10 −5 ; cut‐off values: 4.9 log U/ mL and 4.4 log U/ mL , respectively). In a multivariate Cox regression analysis, patients with persistently high on‐treatment HB crAg levels had a higher risk of HCC than those with low HB crAg levels ( HB eAg+: hazard ratio [ HR ], 6.15, 95% confidence interval [ CI ]: 1.89‐20.0, P = 0.003; HB eAg‐ cohort: HR , 2.54, 95% CI : 1.40‐4.60; P = 0.002). A sub‐analysis of patients without alcoholism yielded similar findings. Conclusions Patients with persistently high on‐treatment HB crAg levels were more likely to develop HCC despite sustained viral suppression via long‐term NA treatment.