Validation of the PAGE-B score to predict hepatocellular carcinoma risk in caucasian chronic hepatitis B patients on treatment

Abstract

Background: Several risk scores have been developed to predict hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. The majority of risk scores are based on pretreatment variables that are no longer considered risk factors for HCC development due to the suppression of hepatitis B virus replication early in the course of potent antiviral treatment in most patients. The PAGE-B score, which is based on platelet levels, age and sex, has been shown to accurately predict HCC risk in CHB patients on antiviral treatment in various populations.

Aim: We aimed to evaluate the PAGE-B score in predicting HCC risk in Turkish CHB patients on antiviral treatment.

Methods: In this study, we recruited 742 CHB patients who had been treated with tenofovir disoproxil fumarate or entecavir for ≥ 1 year. Risk groups were determined according to the PAGE-B scores as follows: ≤ 9, low; 10-17, moderate and ≥ 18, high. The cumulative HCC incidences in each risk group were computed using Kaplan-Meier analysis and were compared using the log-rank test. The accuracy of the PAGE-B score in predicting HCC risk was evaluated using a time-dependent area under the receiver operating characteristic (AUROC) curve at all study time points. Univariate and multivariate logistic regression analyses were used to assess the risk factors for HCC development.

Results: The mean follow-up time was 54.7 ± 1.2 mo. HCC was diagnosed in 26 patients (3.5%). The cumulative HCC incidences at 1, 3, 5 and 10 years were 0%, 0%, 0% and 0.4% in the PAGE-B low-risk group; 0%, 1.2%, 1.5% and 2.1% in the PAGE-B moderate-risk group; and 5%, 11.7%, 12.5%, and 15% in the PAGE-B high-risk group, respectively (log-rank P < 0.001). The AUROCs of the PAGE-B score in the prediction of HCC development at 1, 3, 5 and 10 years were 0.977, 0.903, 0.903 and 0.865, respectively. In the multivariable analysis, older age, male sex, lower platelet levels, presence of cirrhosis, and absence of alanine aminotransferase normalization at month 6 were associated with HCC development (all P < 0.05).

Conclusion: The PAGE-B score is a practical tool to predict HCC risk in Turkish patients with CHB and may be helpful to improve surveillance strategies.

Keywords: Chronic hepatitis B; Hepatocellular carcinoma; PAGE-B score; Surveillance.

Figure 1

Receiver operating characteristic curves of the PAGE-B score for hepatocellular carcinoma development according to years. A: 1^st year; B: 3^rd year; C: 5^th year; D: 10^th year.

Figure 2

Cumulative hepatocellular carcinoma incidences according to PAGE-B risk scores. Low risk vs intermediate risk, log rank P = 0.06; low risk vs high risk, log rank P < 0.001; intermediate risk vs high risk, log rank P < 0.001.