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Risk scores to predict HCC and the benefits of antiviral therapy for CHB patients in gray zone of treatment guidelines

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A Correction to this article was published on 22 January 2024

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Abstract

Backgrounds

ALT ≥ 80 U/L and HBV DNA ≥ 2000 IU/ml are treatment criteria of APASL guidelines for chronic hepatitis B (CHB) patients. The need of antiviral therapy for patients in gray zone (ALT < 80 U/L or HBV DNA < 2000 IU/ml) is controversial. This study aimed to develop a scoring system to predict hepatocellular carcinoma (HCC) and evaluate the benefit of antiviral therapy in these patients.

Methods

Seven hundred and forty-nine patients were analyzed. Significant variables were weighted to develop a scoring system for HCC prediction. The area under receiver operating curves (AUROC) were estimated and validated by REVEAL-HBV cohort (n = 3527).

Results

Older age (p < 0.001), male sex (p = 0.036), family history of HCC (p = 0.002) and HBV DNA ≥ 2000 IU/ml (p = 0.045) were independently associated with HCC. A 14-point risk score system predicts 3 and 5-years HCC risk to be 0.866 and 0.868 of AUROC, respectively in the derivation cohort; 0.821 and 0.820, in the REVEAL-HBV cohort. The cumulative HCC incidence was higher in the high risk (score ≥ 8) group both in derivation and validation cohorts (p < 0.001). Patients with antiviral therapy had lower HCC incidence compared to those without (p = 0.016). Of note, antiviral therapy significantly decreased HCC in the high risk group (p = 0.005), but not in the low risk group (p = 0.705).

Conclusions

A risk scoring system is established and validated. Of CHB patients in gray zone of APASL guidelines, those with risk scores ≥ 8 had higher risk of HCC, but the risk could be significantly reduced by antiviral therapy.

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Change history

Abbreviations

ADV :

Adefovir

AFP :

Alpha-fetoprotein

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CHB:

Chronic hepatitis B

CI:

Confidence interval

CT:

Computed tomography

DFS:

Disease free survival

ER:

Endoplasmic reticulum

ETV:

Entecavir

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HBV–HCC:

HBV related HCC

HCC:

Hepatocellular carcinoma

HDL-C:

High-density lipoprotein cholesterol

HR:

Hazard ratio

LAM:

Lamivudine

LDL-C:

Low-density lipoprotein cholesterol

Ldt:

Telbivudine

MRI:

Magnetic resonance imaging

NA:

Nucleos(t)ide analogues

TAF:

Tenofovir alafenamide

TDF:

Tenofovir disoproxil fumarate

qHBsAg:

Quantitative hepatitis B surface antigen

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Funding

This study was supported by funding from Ministry of Science and Technology (National Science and Technology Council) (104-2314-B-182A-048-MY3; 110-2314-B-A49A-505; 110-2314-B-075-010-MY3), VGHUST Joint Research Program, Tsou Foundation (VGHUST110-G7-3-3), VGHTPE Research Program (V107C-161, V108C-059 and V109C-049), Ministry of Health and Welfare (MOHW107-TDU-B-211-114019; 108-TDU-B-211-124019; 109-TDU-B-211-134019; 110-TDU-B-211-144019) and Cancer Progression Research Center, National Yang-Ming University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education.

Author information

Author notes

  1. Ting-Tsung Chang, Hwai-I Yang, Cheng-Yuan Peng, and Chien-Wei Su equal contribution for 2nd author.

Authors and Affiliations

  1. Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China

    Wei Teng & Jaw-Ching Wu

  2. Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, Republic of China

    Wei Teng

  3. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China

    Ting-Tsung Chang

  4. Genomics Research Center, Academia Sinica, Taipei, Taiwan, Republic of China

    Hwai-I Yang

  5. Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China

    Cheng-Yuan Peng

  6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China

    Chien-Wei Su

  7. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China

    Tung-Hung Su & Hung-Chih Yang

  8. Department of Gastroenterology and Hepatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China

    Tsung-Hui Hu

  9. Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China

    Ming-Lung Yu

  10. Translational Research Division, Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China

    Jaw-Ching Wu

  11. Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China

    Jaw-Ching Wu

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  1. Wei Teng
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Contributions

Concept and design: Wu JC, Su CW; Data acquisition: Wu JC, Su CW, Teng W, Chang TT, Peng CY, Su TH, Yang HC, Yu ML, Hu TH, Yang HI; Manuscript writing: Teng W and Wu JC, Statistical analysis: Teng W, Yang HI, Su CW, Wu JC; Manuscript supervision: Su CW, Wu JC.

Corresponding author

Correspondence to Jaw-Ching Wu.

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Conflicts of interest

Wei Teng, Ting‑Tsung Chang, Hwai‑I Yang, Cheng‑Yuan Peng, Chien‑Wei Su, Tung‑Hung Su, Tsung‑Hui Hu, Ming‑Lung Yu, Hung‑Chih Yang, Jaw‑Ching Wu all authors declared no conflict of interest.

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The study was approved by the Institutional Review Board of each of the participating institutes.

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Teng, W., Chang, TT., Yang, HI. et al. Risk scores to predict HCC and the benefits of antiviral therapy for CHB patients in gray zone of treatment guidelines. Hepatol Int 15, 1421–1430 (2021). https://doi.org/10.1007/s12072-021-10263-x

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