Cirrhosis, Age, and Liver Stiffness-Based Models Predict Hepatocellular Carcinoma in Asian Patients with Chronic Hepatitis B

SIMPLE SUMMARY: Predicting hepatocellular carcinoma in patients with chronic hepatitis B who receive long-term treatment with entecavir or tenofovir is of particular importance in terms of the allocation of medical resources for cancer surveillance. The Cirrhosis and Age (CAGE-B) and Stiffness and Age (SAGE-B) scores were developed to predict hepatocellular carcinoma in Caucasian patients receiving long-term entecavir or tenofovir therapy. In Asian patients who were treated with entecavir or tenofovir, the CAGE-B score predicted the incidence of hepatocellular carcinoma with acceptable accuracy, regardless of the treatment regimen, sex, or hepatic steatosis. Existing prediction models, which showed predictive ability comparable to that of the CAGE-B score, could be used in resource-limited settings where transient elastography is unavailable. ABSTRACT: Objectives: Predicting hepatocellular carcinoma (HCC) in patients with chronic hepatitis B who received long-term therapy with potent nucleos(t)ide analogs is of utmost importance to refine the strategy for HCC surveillance. Methods: We conducted a multicenter retrospective cohort study to validate the CAGE-B and SAGE-B scores, HCC prediction models developed for Caucasian patients receiving entecavir (ETV) or tenofovir (TFV) for >5 years. Consecutive patients who started ETV or TFV at two hospitals in Korea from January 2009 to December 2015 were identified. The prediction scores were calculated, and model performance was assessed using receiver operating characteristics (ROC) curves. Results: Among 1557 patients included, 57 (3.7%) patients had HCC during a median follow-up of 93 (95% confidence interval, 73–119) months. In the entire cohort, CAGE-B predicted HCC with an area under the ROC curve of 0.78 (95% CI, 0.72–0.84). Models that have “liver cirrhosis” in the calculation, such as AASL (0.79 (0.72–0.85)), CU-HCC (0.77 (0.72–0.82)), and GAG-HCC (0.79 (0.74–0.85)), showed accuracy similar to that of CAGE-B (p > 0.05); however, models without “liver cirrhosis”, including SAGE-B (0.71 (0.65–0.78)), showed a lower predictive ability than CAGE-B. CAGE-B performed well in subgroups of patients treated without treatment modification (0.81 (0.73–0.88)) and of male sex (0.79 (0.71–0.86)). Conclusions: This study validated the clinical usefulness of the CAGE-B score in a large number of Asian patients treated with long-term ETV or TFV. The results could provide the basis for the reappraisal of HCC surveillance strategies and encourage future prospective validation studies with liver stiffness measurements.