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2116
Hepatitis B Core-Related Antigen (HΒcrΑg)
Is a Novel Risk Marker for Hepatocellular
Carcinoma during Nucleoside Analogue
Treatment
Hatsue Fujino, Department of Gastroenterology and
Metabolism, Hiroshima University and Kazuaki Chayama,
Department of Gastroenterology and Metabolism, Institute of
Biomedical & Health Science, Hiroshima University
Background: Patients infected with hepatitis B virus (HBV)
are at high risk of developing liver cirrhosis and hepatocellular
carcinoma (HCC). Although nucleos(t)ide analogues (NAs)
treatment has made it possible to control HBV chronic
liver diseases, risk of liver carcinogenesis still remains.
Recently, hepatitis B core-related antigen (HBcrAg) has been
reported as a serological marker for disease monitoring and
prognostication of chronic hepatitis B. We assessed risk
factors of HCC development in patients infected with HBV
during NAs therapy including HBcrAg. Methods: This study
included HBV infected patients induced NAs (Lamivudine,
Adefovir, Entecavir, Tenofovir) without HCC. The following
exclusion criteria were applied: 1) co-infected with hepatitis
C, or human immunodeficiency virus, 2) autoimmune
hepatitis, or primary biliary cholangitis, 3) acute liver failure
at first visit, 4) breakthrough hepatitis during the follow-up
period, 5) prevention for HBV reactivation, and 6) history of
hepatic transplantation. HBcrAg was measured before or
after the introduction of NA treatment. This study included
486 patients out of 2229 HBV infected patients visited
Hiroshima University hospital between January 1986 and
December 2017. The primary end point was the development
of HCC. The cumulative incidence and risk factors of HCC
were evaluated by the Kaplan-Meier method and multivariate
Cox proportional hazards models. The study was approved
by the institutional ethical review board. Results: Seventy
three out of 486 patients have developed HCC during the
follow-up period. The Kaplan-Meier method identified age
(51 ≤, P < 0.0001), male (P = 0.0106), Platelet count (≤ 15.9
× 104 /μL, P = 0.0002), HBcrAg level (3.7 log U/mL ≤, P <
0.0001), Aspartate aminotransferase level (38.5 U/L ≤, P =
0.0443), Total bilirubin (T-Bil) level (0.8 mg/dL ≤, P = 0.0025)
and Albumin level (≤ 4.1 g/dL, P = 0.0003) as significant risk
factor for HCC. Multivariate analysis identified HBcrAg level
(hazard ratio [HR], 15.380; P < 0.001), platelet count (HR,
2.652; P = 0.015) and T-Bil level (HR, 2.668; P < 0.0029) as
significant risk factor for HCC. Conclusion: Higher HBcrAg
level, higher total bilirubin level and lower platelet count
were associated with an increased risk of developing HCC in
patients undergoing NAs treatment. HBcrAg could be a novel
risk marker for predicting patients who develop HCC after
inducing NAs treatment.
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