Detectable HBV DNA during nucleos(t)ide analogues stratifies predictive hepatocellular carcinoma risk score

Shun Kaneko,Atsunori Kusakabe,Takehiko Abe,Hiroyuki Kimura,Hiroyuki Marusawa,Takehiro Akahane,Yasushi Uchida,Masahiko Kondo,Hitoshi Yagisawa,Chitomi Hasebe,Haruhiko Kobashi,Yuji Kojima,Hideo Yoshida,Masayuki Kurosaki,Kouji Joko,Sakura Kirino,Nobuharu Tamaki,Keiji Tsuji,Tomomichi Matsushita,Namiki Izumi

doi:10.1038/s41598-020-69522-w

Abstract

Nucleos(t)ide analogs (NA) suppress hepatitis B virus (HBV) replication and reduce the risk of hepatocellular carcinoma (HCC). However, NA cannot suppress carcinogenesis completely in patients with chronic hepatitis B. The aims of this study were to identify risk factors for HCC and develop a refined carcinogenesis prediction model. Patients receiving NA therapy (n = 1,183) were recruited retrospectively from the 16 hospitals. All patients had been receiving NA continuously for more than 1 year until the end of the follow-up. During a median follow-up of 4.9 (1.0–12.9) years, 52 (4.4%) patients developed HCC. A multivariate analysis revealed that male gender, older age, lower platelet counts at the baseline, and detectable HBV DNA during NA therapy were independent predictive factors of HCC development. The PAGE-B score was calculated by using these factors. 240 (20.3%), 661 (55.9%), and 282 (23.8%) patients were classified into low-, intermediate-, and high-risk groups, respectively. In the intermediate- and high-risk group, detectable HBV DNA was significantly associated with a higher risk of HCC development compared with continuously undetectable HBV DNA, respectively (HR 3.338; 95% CI 1.045–10.66/HR 3.191; 95% CI 1.543–6.597). PAGE-B–DNA, which is the combined PAGE-B and HBV DNA status, was valuable for a more refined stratification of PAGE-B.

Highlights

Nucleos(t)ide analogs (NA) suppress hepatitis B virus (HBV) replication and reduce the risk of hepatocellular carcinoma (HCC)
In addition to the baseline characteristics that were used for the analysis of factors associated with HCC, we focused on the HBV DNA status during NA therapy
This study provides the first evidence that HBV DNA status on NA therapy is useful for subdividing further the PAGE-B score

Summary

Introduction

Nucleos(t)ide analogs (NA) suppress hepatitis B virus (HBV) replication and reduce the risk of hepatocellular carcinoma (HCC). The aims of this study were to identify risk factors for HCC and develop a refined carcinogenesis prediction model. In the intermediate- and high-risk group, detectable HBV DNA was significantly associated with a higher risk of HCC development compared with continuously undetectable HBV DNA, respectively (HR 3.338; 95% CI 1.045–10.66/HR 3.191; 95% CI 1.543–6.597). Several studies reported that complete viral suppression reduced the risk of developing HCC23–25. We attempted to construct a prediction HCC model in CHB patients receiving NA therapy using a well-designed representative risk score of the host (PAGE-B) or of the virus (HBV DNA status). The aims of this study were to develop a refined carcinogenesis prediction model based on conventional prediction models (PAGE-B and serum HBV DNA) in patients receiving NA therapy. We assessed that the HBV DNA status on NA therapy discriminated the PAGE-B intermediate-risk group and the high-risk group

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Conclusion