Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2021; 27(17): 2025-2038
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.2025
Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study
Dan-Hong Yang, Wei-Ping Wang, Qiang Zhang, Hong-Ying Pan, Yi-Cheng Huang, Jia-Jie Zhang
Dan-Hong Yang, Hong-Ying Pan, Yi-Cheng Huang, Jia-Jie Zhang, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Wei-Ping Wang, Qiang Zhang, Postgraduate Department, Bengbu Medical College, Bengbu 233030, Anhui Province, China
Author contributions: Yang DH designed the research study; Yang DH and Wang WP analyzed the data and wrote the manuscript; Zhang Q, Pan HY, Huang YC and Zhang JJ collected the data; All authors have read and approved the final manuscript.
Supported by Zhejiang Provincial Natural Science Foundation, No. LY18H190002.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Zhejiang Provincial People’s Hospital (2020QT155, Hangzhou, Zhejiang Province, China).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Dan-Hong Yang, PhD, Chief Doctor, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China.
Received: January 31, 2021
Peer-review started: January 31, 2021
First decision: March 14, 2021
Revised: March 25, 2021
Accepted: April 2, 2021
Article in press: April 2, 2021
Published online: May 7, 2021

Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma (HCC). Furthermore, there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog (NA) therapy.


The study aim was to clarify risk factors and the diagnostic value of alpha-fetoprotein (AFP) for HCC progression in NA-treated hepatitis B virus (HBV)-related cirrhosis patients.


In this retrospective cross-sectional study, we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital. The patients were divided into two groups, 145 who did not progress to HCC (No-HCC group), and 121 who progressed to HCC during NA treatment (HCC group). The logistic regression analysis was used to analyze the risk factors of HCC progression. The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic (ROC) curve analysis.


Univariate analysis showed that age ≥ 60 years (P = 0.001), hepatitis B and alcoholic etiology (P = 0.007), smoking history (P < 0.001), family history of HBV-related HCC (P = 0.002), lamivudine resistance (P = 0.011), HBV DNA negative (P = 0.023), aspartate aminotransferase > 80 U/L (P = 0.002), gamma-glutamyl transpeptidase > 120 U/L (P = 0.001), alkaline phosphatase > 250 U/L (P = 0.001), fasting blood glucose (FBG) ≥ 6.16 (mmol/L) (P = 0.001) and Child-Pugh class C (P = 0.005) were correlated with HCC progression. In multivariate analysis, age ≥ 60 years [hazard ratio (HR) = 3.089, 95% confidence interval (CI): 1.437-6.631, P = 0.004], smoking history (HR = 4.001, 95%CI: 1.836-8.716, P < 0.01), family history of HBV-related HCC (HR = 6.763, 95%CI: 1.253-36.499, P < 0.05), lamivudine resistance (HR = 2.949, 95%CI: 1.207-7.208, P = 0.018), HBV DNA negative (HR = 0.026, 95%CI: 0.007-0.139, P < 0.01), FBG ≥ 6.16 mmol/L (HR = 7.219, 95%CI: 3.716-14.024, P < 0.01) were independent risk factors of HCC progression. ROC of AFP for diagnosis of HCC was 0.746 (95%CI: 0.674-0.818). A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609, and specificity of 0.818 for diagnosing HCC.


Age ≥ 60 years, smoking history, family history of HCC, lamivudine resistance, HBV DNA negative, FBG ≥ 6.16 mmol/L were risk factors of HCC progression. Serum AFP had limited diagnostic value for HCC.

Keywords: Hepatitis B virus, Hepatocellular carcinoma, Cirrhosis, Risk factors, Nucleos(t)ide analogs, Progression

Core Tip: This retrospective cross-sectional study analyzed risk factors of hepatocellular carcinoma (HCC) progression in hepatitis B virus-related cirrhosis patients receiving nucleoside acid analog therapy for at least 6 mo. We discuss the diagnostic value of serum alpha-fetoprotein level in these patients. The results of the present study increase our understanding of HCC pathogenesis and help to provide HCC prevention and control strategies.