Risk Factors and Nomogram Model for Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients with Low-Level Viremia

Abstract

Background and aim: Patients with chronic hepatitis B patients (CHB) with low-level viremia (LLV) are not necessarily at low risk of developing hepatocellular carcinoma (HCC). The question of whether CHB patients with LLV require immediate antiviral agent (AVT) or long-term AVT remains controversial. The study aims to investigate the risk of HCC development and the risk factors in CHB patients with LLV and construct a nomogram model predicting the risk of HCC. Methods: We conducted a retrospective cohort study that enrolled 16,895 CHB patients from January 2008 to December 2020. The patients were divided into three groups for comparison: the LLV group, maintained virological response (MVR) group and HBV-DNA>2000 group. The cumulative incidence of progression to HCC was assessed. Cox regression analysis was performed to determine the final risk factors, and a nomogram model was constructed. The 10-fold Cross-Validation method was utilized for internal validation. Results: A total of 408 new cases of HCC occurred during the average follow-up period of 5.78 years. The 3, 5, and 10-year cumulative HCC risks in the LLV group were 3.56%, 4.96%, and 9.51%, respectively. There was a significant difference in the cumulative risk of HCC between the HBV-DNA level > 2000 IU/mL and LLV groups (p = 0.049). Independent risk factors for HCC development in LLV group included male gender, age, presence of cirrhosis, and platelets count. The Area Under the Curve (AUC) values for the 3-year and 5-year prediction from our HCC risk prediction model were 0.75 and 0.76, respectively. Conclusion: Patients with LLV and MVR are still at risk for developing HCC. The nomogram established for CHB patient with LLV, incorporating identified significant risk factors, serves as an effective tool for predicting HCC-free outcomes. This nomogram model provides valuable information for determining appropriate surveillance strategies and prescribing AVT.

Keywords: HBV; HCC; Low viral load; Taiwan; nomogram.

Figure 1

Cumulative incidence of hepatocellular carcinoma according to HBV-DNA levels. Abbreviations: HCC: hepatocellular carcinoma. HBV: Hepatitis B virus.

Figure 2

Nomogram predicting the risk of hepatocellular carcinoma in patients with chronic hepatitis B. Abbreviations: HCC: hepatocellular carcinoma. HBV: Hepatitis B virus. AST: aspartate aminotransferase.

Figure 3

(A) Time-dependent AUC of three years HCC-free in patients with chronic hepatitis B. (B) Time-dependent AUC of five years HCC-free in patients with chronic hepatitis B. Abbreviations: ROC: receiver operating characteristic. AUC: area under the ROC curve. HCC: hepatocellular carcinoma.

Figure 4

Integrated time-dependent AUC to predict HCC-free in patients with chronic hepatitis B. Abbreviations: AUC: area under the ROC curve. HCC: hepatocellular carcinoma.