Direct-Acting Antiviral Agents Reduce the Risk of Malignant Transformation of Hepatobiliary Phase-Hypointense Nodule without Arterial Phase Hyperenhancement to Hepatocellular Carcinoma on Gd-EOB-DPTA-Enhanced Imaging in the Hepatitis C Virus-Infected Liver

Background and Aims: Hepatobiliary phase-hypointense nodules without arterial phase hyperenhancement (HHNs without APHE) on gadolinium-ethoxybenzyl-diethylenetriamine-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) are considered to be dysplastic nodules or early hepatocellular carcinoma (HCC) and have high risk of undergoing malignant transformation and progression to hypervascular HCC. The aim of this study was to evaluate the clinical outcome of HHNs without APHE diagnosed by Gd-EOB-DTPA-enhanced MRI before the eradication of HCV by direct-acting antiviral agents (DAAs). Methods: We retrospectively investigated 221 consecutive patients with HCV infection who were treated with DAAs. Thirty patients with 65 HHNs without APHE were enrolled in a sustained virologic response (SVR) cohort and 22 with 43 HHNs without APHE who did not receive DAAs or had failed HCV eradication therapy were enrolled in a non-SVR cohort. Fifty-seven percent of patients in the SVR group and 64% of those in the non-SVR group had a history of HCC. The primary endpoint of this study was the development of hypervascular HCC from HHNs without APHE detected on imaging. The cumulative incidence and relative risk of progression to hypervascular HCC in relation to clinical characteristics were compared between the two cohorts. Results: The 2-year cumulative incidence of progression to hypervascular HCC was 8.5 and 21.9% in the SVR and non-SVR cohorts, respectively. There was a significant reduction in progression of HHNs without APHE to HCC after the eradication of HCV (p = 0.022, log-rank test). Multivariate Cox regression analysis identified hyperintensity on T2-weighted images (relative risk 14.699, p < 0.001) and achieving SVR (relative risk 0.290, p = 0.043) as independent factors associated with the risk of HCC. During follow-up, 6 (9.2%) of the HHNs without APHE in the SVR cohort became undetectable on hepatocyte-phase images. Conclusions: Eradication of HCV by DAAs could reduce the hypervascularization rate of HHNs without APHE, and some of these nodules disappeared.