Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals

      Background & Aims

      Hepatocellular carcinoma (HCC) represents a serious complication of HCV-related cirrhosis. New direct-acting antivirals (DAA) cure HCV infection in over 90% of patients. The aim of this study was to evaluate the early occurrence and recurrence of HCC in cirrhotic patients treated with DAA.


      We analysed 344 consecutive cirrhotic patients, without HCC, who were treated with DAA, and followed for 24 weeks. Fifty-nine patients had previous HCC.


      DAA therapy induced sustained virological response in 91% of patients. During 24-week follow-up, HCC was detected in 26 patients (7.6%, 95% CI: 4.99–10.84): 17 of 59 patients (28.81%, 95% CI: 17.76–42.07) with previous HCC and 9 of 285 patients (3.16%, 95% CI: 1.45–5.90) without previous HCC. Child-Pugh Class B, more severe liver fibrosis, lower platelet count, and previous HCC were significantly associated with HCC development, at univariate analysis. At multivariate analysis, Child-Pugh class (p = 0.03, OR: 4.18, 95% CI: 1.17–14.8) and history of HCC (p <0.0001, OR: 12.0, 95% CI: 4.02–35.74) resulted independently associated with HCC development. Among the 59 patients with previous HCC, younger age and more severe liver fibrosis were significantly associated with HCC recurrence, both at univariate and at multivariate analysis.


      In patients with HCV-related cirrhosis, DAA-induced resolution of HCV infection does not seem to reduce occurrence of HCC, and patients previously treated for HCC have still a high risk of tumour recurrence, in the short term. For these reasons, all cirrhotic patients should be closely monitored and followed during and after antiviral therapy.

      Lay summary

      New direct-acting antivirals are able to eradicate HCV infection in over 90% of patients with advanced liver disease. Unfortunately, the occurrence of liver cancer is not reduced in effectively treated cirrhotic patients. In addition, patients previously treated for HCC have still a high risk of tumour recurrence in the short term, despite DAA treatment.

      Graphical abstract


      HCC (hepatocellular carcinoma), DAA (direct-acting antivirals), HCV (hepatitis C virus), SVR (sustained virological response), AIFA (Italian Medicines Agency), CEUS (contrast-enhanced ultrasonography), CT (computerized tomography), MRI (magnetic resonance imaging), RFA (radiofrequency ablation), TACE (trans-arterial chemoembolization), PEI (percutaneous ethanol injection), ROC (receiver operating characteristics), kPa (kilo Pascal), MELD (model for end stage liver disease), HBsAg (hepatitis B surface antigen), BMI (body mass index), SVR12 (sustained virological response 12weeks after treatment completion), SOF (sofosbuvir), SMV (simeprevir), 3D (ombitasvir, paritaprevir with ritonavir, and dasabuvir), RBV (ribavirin), DCV (daclatasvir), LDV (ledipasvir), AFP (α-fetoprotein), BCLC (Barcelona Clinic Liver Cancer)


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      Author names in bold designate shared co-first authorship

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