# Prediction of Hepatocellular Carcinoma After Direct‐Acting Antiviral Therapy Using Agile 3+ and End‐of‐Treatment Alpha‐Fetoprotein Levels in Patients With Hepatitis C

## TL;DR

This study shows that combining Agile 3+ scores and alpha-fetoprotein levels after treatment can help predict the risk of liver cancer in hepatitis C patients who achieved a virus-free state.

## Contribution

A new scoring system combining Agile 3+ and end-of-treatment alpha-fetoprotein levels is proposed for predicting hepatocellular carcinoma risk after DAA therapy.

## Key findings

- 15 out of 337 patients (4.5%) developed hepatocellular carcinoma during follow-up.
- Patients with a score of ≥1 had significantly higher HCC risk (p < 0.001).
- Agile 3+ score ≥0.9398 and EOT-AFP ≥3.8 ng/mL were independent predictors of HCC.

## Abstract

Direct‐acting antivirals (DAAs) have dramatically improved sustained virological response (SVR) rates in patients with hepatitis C virus (HCV) infection. However, the risk of hepatocellular carcinoma (HCC) remains even after achieving SVR. We previously reported that alpha‐fetoprotein (AFP) levels at the end of treatment (EOT) were associated with the occurrence of HCC after achieving sustained virologic response (SVR). Here, to improve predictive accuracy by incorporating the Agile 3+ score among 502 patients who received DAA therapy for HCV infection between September 2017 and July 2024, we excluded those who developed HCC within 1 year of treatment and included 337 patients with chronic hepatitis or compensated cirrhosis, who had no prior HCC and underwent transient elastography before treatment. A scoring system was developed by assigning 1 point for Agile 3+ score ≥ 0.9398 and 1 point for EOT‐AFP ≥ 3.8 ng/mL. The cumulative HCC incidence was analyzed in relation to the total score. Cox proportional hazards models were used to assess independent risk factors. During follow‐up, 15 patients (4.5%) developed HCC. Patients with a score of ≥ 1 had a significantly higher HCC risk (p < 0.001). Agile 3‐AFP score ≥ 1 (hazard ratio (HR) 12.65, 95% CI 1.38–115.49, p = 0.02) and GGT (HR 1.00, 95% CI 1.00–1.01, p = 0.02) remained independent predictors of HCC occurrence. A simple scoring system combining the pretreatment Agile 3+ score and EOT‐AFP levels may be useful for long‐term risk stratification of HCC after DAA therapy in HCV‐infected patients.