AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy

Abstract

Background: An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment.

Methods: Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as 'early recurrence', and recurrence more than 1 year after as 'late recurrence'. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated.

Results: Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026-1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96-0.99, p = 0.032) as a predictor of HCC recurrence in the late phase.

Conclusion: Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

Keywords: DAA; Diabetes mellitus; Follow-up; HCV; Male; Number of treatments; Prediction; Renal function; Risk factor; SVR; Sex; Time of recurrence; Treatment history.

Fig. 1

Cumulative recurrence (%) of hepatocellular carcinoma (HCC) after DAA therapy by Kaplan-Meier method

Fig. 2

Comparison of cumulative HCC recurrence (%) by sex (A). Cumulative HCC recurrence is significantly higher in males than in females, according to the log-rank test (p = 0.017). Comparison of cumulative HCC recurrence (%) by sustained virological response (SVR) achievement (B). Cumulative HCC recurrence is significantly higher in the ‘no SVR’ group than in the group with SVR according to the log-rank test (p = 0.003). Comparison of cumulative HCC recurrence (%) between the group with more than two past HCC treatments and the group with only one HCC treatment (C). Cumulative HCC recurrence is significantly higher in the group with more than two past HCC treatments according to the log-rank test (p = 0.001). Cumulative recurrence (%) of HCC according to the score combining sex, SVR achievement, and number of past HCC treatments (D). Study patients are grouped based on these scores: 0 points, low-risk group (n = 39); 1 or 2 points, intermediate-risk group (n = 88); and 3 points, high-risk group (n = 72). Cumulative HCC recurrence increases significantly with higher scores (p < 0.001)

Fig. 3

Comparison of cumulative HCC recurrence (%) in the early phase (within 1 year after DAA treatment) by post-treatment AFP ≥6.0 ng/mL (A). Cumulative HCC recurrence in the early phase is significantly higher in the high-AFP group than in the low-AFP group according to the log-rank test (p = 0.040). Comparison of cumulative HCC recurrence (%) in the late phase (more than 1 year after DAA treatment) by post-treatment eGFR ≤70 mL/min/1.73 m² (B). Cumulative HCC recurrence in the late phase is significantly higher in the low-eGFR group than in the high-eGFR group according to the log-rank test (p = 0.008). Comparison of cumulative HCC recurrence (%) in the late phase in patients with post-treatment eGFR > 70 mL/min/1.73 m² between groups with and without diabetes mellitus (DM) (C). Cumulative HCC recurrence in the late phase is significantly higher in the group with DM than in the group without DM according to the log-rank test (p = 0.019)