Addition of liver stiffness enhances the predictive accuracy of the PAGE‐B model for hepatitis B‐related hepatocellular carcinoma

Abstract

B models reliably predict the risk of developing chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). Aim(s): To investigate whether the addition of liver stiffness (LS) value, assessed using transient elastography, enhanced the predictive accuracies of these models Methods: Patients with CHB who started anti-viral therapy (AVT) between 2007 and 2017 were enrolled. The training (Yonsei University Hospital) and validation (seven Korean referral institutes) cohorts contained 1211 and 973 patients, respectively. Results: Based on multivariate analysis, older age (hazard ratio [HR] = 1.051, 95% confidence interval [CI] = 1.031-1.071), male sex (HR = 2.265, 95% CI = 1.463-3.506), lower platelet count (HR = 0.993, 95% CI = 0.989-0.997) and greater LS values (HR = 1.015, 95% CI = 1.002-1.028) were independently associated with an increased risk of HCC development (all P < 0.05). Thus, we developed a modified PAGE LS-B model (maximum score 34) that included age, male sex, platelet count and LS value. The integrated area under the curve of the modified PAGE LS model was greater than those of the PAGE-B and mPAGE-B models (0.760 vs 0.714 and 0.716, respectively) in the derivation dataset. The cumulative HCC incidence was significantly higher in the high-risk (modified PAGE-B LS score ≥ 24) group than in the intermediate-risk (modified PAGE LS-B score 12-24) or low-risk (modified PAGE LS-B score < 12) group (all P < 0.001). Similar results were observed in the validation cohort.

KASL clinical practice guidelines for management of chronic hepatitis B

“…Modified REACH-B (mREACH-B) model, which substituted serum HBV DNA for the liver stiffness value from the original REACH-B model, showed better outcomes in assessment of 3-year and 5-year HCC prediction in several prospective Korean studies [ 86 , 87 ]. Meanwhile, PAGE-B (platelets, age, gender, and hepatitis B) model, which was developed from Western studies [ 88 ], has been validated by several Korean retrospective studies [ 89 , 90 ]. Modified PAGE-B (adding serum albumin) was superior to the original PAGE-B in prediction of 5-year HCC risk in Korean CHB patients [ 90 - 92 ].…”

“…Meanwhile, PAGE-B (platelets, age, gender, and hepatitis B) model, which was developed from Western studies [ 88 ], has been validated by several Korean retrospective studies [ 89 , 90 ]. Modified PAGE-B (adding serum albumin) was superior to the original PAGE-B in prediction of 5-year HCC risk in Korean CHB patients [ 90 - 92 ]. Although THRI (Toronto HCC risk index) has shown good predictive ability for HCC in patients with cirrhosis [ 93 ], it was not superior to mPAGE-B in Korean CHB patients [ 91 ].…”

Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection

“…The performance of modified PAGE LS -B model for predicting HBV-related HCC risk was superior to the PAGE-B and mPAGE-B models (AUROC value 0.760 vs. 0.714 and 0.716, respectively). 139 Thus, dynamic assessment of HCC risk through liver stiffness-based prediction models should be incorporated to the strategy of HCC surveillance for patients receiving antiviral therapy.…”

The best predictive model for hepatocellular carcinoma in patients with chronic hepatitis B infection

“…Among these models, the HCC-RESCUE and APA-B models were developed from studies that were conducted only on patients who were treated with ETV while the remaining models, the PAGE-B, CAMD, and AASL models were developed from studies on patients who were treated with either ETV or TDF. In addition to these models, studies that have been conducted in Asia have developed the HCC-RESCURE (risk estimating score in CHB patients using entecavir), mREACH-B, PAGE-B-LS and the APA-B models [34,35,39,40].…”