External Validation of the FSAC Model Using On-Therapy Changes in Noninvasive Fibrosis Markers in Patients with Chronic Hepatitis B: A Multicenter Study

SIMPLE SUMMARY: We externally validated the recently suggested FSAC prediction model for hepatocellular carcinoma (HCC) in treatment-naïve Asian chronic hepatitis B patients starting potent antiviral therapy (AVT). The model reflects age, sex, presence of cirrhosis, and on-therapy changes in non-invasive fibrosis markers (NFMs) after 12 months of antiviral therapy, such as APRI and FIB-4. Our results highlighted better predictive performance for the FSAC model for HCC (Harrell’s c-index: 0.770) than the PAGE-B, modified PAGE-B, modified REACH-B, LSM-HCC, and CAMD models, which only use baseline parameters. A simplified version of FSAC score (i.e., FSAC (2)), including only NFMs at 12 months, also showed a high c-index value (0.763). Our retrospective study suggests that the accurate measurement of intra-hepatic fibrotic burden during adequate AVT is necessary for predicting HCC development. ABSTRACT: Antiviral therapy (AVT) induces the regression of non-invasive fibrosis markers (NFMs) and reduces hepatocellular carcinoma (HCC) risk among chronic hepatitis B (CHB) patients. We externally validated the predictive performance of the FSAC prediction model for HCC using on-therapy NFM responses. Our multicenter study consecutively recruited treatment-naïve CHB patients (n = 3026; median age, 50.0 years; male predominant (61.3%); cirrhosis in 1391 (46.0%) patients) receiving potent AVTs for >18 months between 2007 and 2018. During follow-up (median 64.0 months), HCC developed in 303 (10.0%) patients. Patients with low FIB-4 or APRI levels at 12 months showed significantly lower HCC risk than those with high NFM levels at 12 months (all p < 0.05). Cumulative 3-, 5-, and 8-year HCC probabilities were 0.0%, 0.3% and 1.2% in the low-risk group (FSAC ≤ 2); 2.1%, 5.2%, and 11.1% in the intermediate-risk group (FSAC 3−8); and 5.2%, 15.5%, and 29.8% in the high-risk group (FSAC ≥ 9) (both p < 0.001 between each adjacent pair). Harrell’s c-index value for FSAC score (0.770) was higher than those for PAGE-B (0.725), modified PAGE-B (0.738), modified REACH-B (0.737), LSM-HCC (0.734), and CAMD (0.742). Our study showed that the FSAC model, which incorporates on-therapy changes in NFMs, had better predictive performance than other models using only baseline parameters.