Risk of Liver and Non-Liver Malignancy in HCV-Infected Patients with Cirrhosis After Direct-Acting Antiviral Treatment

Background: Patients with liver cirrhosis remain at a persistent risk of developing hepatocellular carcinoma (HCC) and liver decompensation even after hepatitis C virus (HCV) eradication. Objectives: We aimed to assess survival, the occurrence of recompensation and de novo decompensation events, and hepatic and extrahepatic malignancies in patients with liver cirrhosis during long-term observation (LTO) after direct-acting antiviral (DAA) treatment. Methods: The study population consisted of 326 consecutive HCV-infected patients with liver cirrhosis treated with DAAs between 1 July 2015 and 30 June 2025 at a single tertiary hepatology center, of whom we followed 298 individuals for a median (IQR) of 4.4 (2.4–8.1) years after treatment completion. Results: Men predominated in the study population, with a median age of 60 (48–69) years. The vast majority of patients had at least one comorbid condition. Fifty of them (16.8%) developed malignancies during LTO, including 33 cases of HCC and 17 with extrahepatic malignancies. New cases of HCC were documented as late as 9 years after DAA therapy. Overall, 103 patients (34.6%) died during LTO; 51 deaths occurred in patients with malignancies. Liver recompensation was observed in 27.8% of patients, while 9.9% experienced de novo decompensation events during LTO. The survival curve showed a gradual decline in survival probability from 0.96 at 1–2 years to 0.70 at 5 years and 0.51 at 10 years. Conclusions: Patients with cirrhosis should remain under long-term hepatological monitoring after antiviral treatment, as they are still at risk of liver decompensation and the development of de novo HCC.