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Incidence and predictors of hepatocellular carcinoma beyond year 5 of entecavir therapy in chronic hepatitis B patients

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Abstract

Background

Purpose

The study compared the incidence and predictors of hepatocellular carcinoma (HCC) within and beyond year 5 of entecavir (ETV) therapy.

Methods

The study enrolled 1397 CHB patients who were naïve to nucleos(t)ide analogue (NA) treatment and had received ETV monotherapy for more than 12 months.

Results

The cumulative incidences of HCC at 3, 5, and 10 years of ETV treatment were 4%, 9.1%, and 15.8%, respectively. In the entire cohort, the annual incidence rates of HCC were 2.28% within the first 5 years and 1.34% within 5–10 years of therapy. The incidences of HCC did not differ significantly within and beyond 5 years of ETV therapy (p = 0.53), including patients with cirrhosis (p = 0.85) and without cirrhosis (p = 0.47). At year 5 of treatment, the multivariate analysis showed that the fibrosis-4 (FIB-4) index and alpha-fetoprotein (AFP) levels were independent risk factors for HCC development beyond year 5. The 10-year cumulative incidences of HCC beyond year 5 in the high-risk group (FIB-4 > 2.20 and AFP > 3.21 ng/mL) and low-risk group (FIB-4 ≤ 2.20 and AFP ≤ 3.21 ng/mL) were 48.7% and 0%, respectively. APA-B score at 12 months and year 5 had a higher C-index for the prediction of HCC beyond year 5 than the PAGE-B at baseline and year 5 (p = 0.003 and p = 0.039, respectively)

Conclusions

The HCC incidence tended to decrease but did not change significantly within and beyond 5 years of ETV therapy. The FIB-4 index and AFP levels at year 5 were predictive of HCC development beyond year 5 of ETV therapy.

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Abbreviations

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

NA:

Nucleos(t)ide analogue

ETV:

Entecavir

CHB:

Chronic hepatitis B

HCV:

Hepatitis C virus

FIB-4:

Fibrosis-4

HBsAg:

Hepatitis B surface antigen

AFP:

Alpha-fetoprotein

VR:

Virological response

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

HBeAg:

Hepatitis B e antigen

CI:

Confidence interval

TDF:

Tenofovir disoproxil fumarate

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Acknowledgements

The authors would like to thank Ms. Chia-Hsin Lin for statistical analysis.

Funding

This study was supported by grants CMRPG8D1181 and CMRPG891481 from Chang Gung Memorial Hospital, Taiwan, and DMR-101-011 from China Medical University Hospital, Taichung, Taiwan.

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Authors and Affiliations

  1. Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan

    Fai-Meng Sou, Tsung-Hui Hu, Chao-Hung Hung, Jing-Houng Wang, Sheng-Nan Lu & Chien-Hung Chen

  2. Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan

    Hsueh-Chou Lai & Cheng-Yuan Peng

  3. School of Medicine, China Medical University, Taichung, Taiwan

    Cheng-Yuan Peng

Authors
  1. Fai-Meng Sou
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  2. Tsung-Hui Hu
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  4. Hsueh-Chou Lai
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Corresponding authors

Correspondence to Cheng-Yuan Peng or Chien-Hung Chen.

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Conflict of interest

Cheng-Yuan Peng has served as an advisory committee member for AbbVie, BMS, Gilead, and MSD. The coauthors have no conflicts of interest to declare.

Ethical statement

All procedures performed in studies were in accordance with the ethical standards of Research Ethics Committees of Chang Gung Memorial Hospital (approval number: 103-8378A3) and China Medical University Hospital (approval number: CMUH102-REC1-113) at which the studies were conducted.

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Sou, FM., Hu, TH., Hung, CH. et al. Incidence and predictors of hepatocellular carcinoma beyond year 5 of entecavir therapy in chronic hepatitis B patients. Hepatol Int 14, 513–520 (2020). https://doi.org/10.1007/s12072-020-10031-3

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  • DOI: https://doi.org/10.1007/s12072-020-10031-3

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