Predictive Risk Factors and Scoring Systems Associated with the Development of Hepatocellular Carcinoma in Chronic Hepatitis B

Abstract

Chronic hepatitis B (CHB) infection constitutes a leading cause of hepatocellular carcinoma (HCC) development. The identification of HCC risk factors and the development of prognostic risk scores are essential for early diagnosis and prognosis. The aim of this observational, retrospective study was to evaluate baseline risk factors associated with HCC in CHB. Six hundred thirty-two consecutive adults with CHB (n = 632) [median age: 46 (IQR: 24)], attending the outpatients’ Hepatology clinics between 01/1993–09/2020 were evaluated. Core promoter mutations and cirrhosis-HCC (GAG-HCC), Chinese University-HCC (CU-HCC), risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B), Fibrosis-4 (FIB-4), and Platelet Age Gender–HBV (PAGE-B) prognostic scores were calculated, and receiver operating curves were used to assess their prognostic performance. HCC was developed in 34 (5.38%) patients. In the multivariable Cox regression analysis, advanced age (HR: 1.086, 95% CI: 1.037–1.137), male sex (HR: 7.696, 95% CI: 1.971–30.046), alcohol abuse (HR: 2.903, 95% CI: 1.222–6.987) and cirrhosis (HR: 21.239, 95% CI: 6.001–75.167) at baseline were independently associated with the development of HCC. GAG-HCC and PAGE-B showed the highest performance with c-statistics of 0.895 (95% CI: 0.829–0.961) and 0.857 (95% CI: 0.791–0.924), respectively. In the subgroup of patients with cirrhosis, the performance of all scores declined. When treated and untreated patients were studied separately, the discriminatory ability of the scores differed. In conclusion, HCC development was independently associated with advanced age, male sex, alcohol abuse, and baseline cirrhosis among a diverse population with CHB. GAG-HCC and PAGE-B showed high discriminatory performance to assess the risk of HCC development in these patients, but these performances declined in the subgroup of patients with cirrhosis. Further research to develop scores more specific to certain CHB subgroups is needed.