Predictive Factors Differ between Hepatocellular Carcinoma Occurrence and Recurrence after Sustained Virological Responses by Direct-Acting Antivirals in Patients with Hepatitis C

Abstract

Background: Interferon-free direct-acting antivirals (DAA) have markedly increased the sustained virological response (SVR) rate among patients with hepatitis C. Although DAA inhibit the development of hepatocellular carcinoma (HCC), predictive factors remain unclear. The aims of the present study were to investigate predictive factors for HCC occurrence and recurrence after SVR by DAA in prospectively followed patients with hepatitis C (HCV). Methods: One hundred and eighty-three HCV-infected patients treated with DAA and achieving SVR were prospectively followed up for more than one year. Among these patients, 166 had no history of HCC before DAA therapy, while 17 had a history of being treated for HCC by radiofrequency ablation or resection before the initiation of DAA. Liver stiffness (LS) measurements were conducted using transient elastography, and LS was assessed at the initiation of DAA (LS0), 24 weeks after the initiation of DAA (LS24), 48 weeks after (LS48), and every year after that. Results: HCC occurred in 7 out of 166 patients without a history of HCC (4.2%), and recurred in 9 out of 17 with a history of HCC (52.9%). Patients with a history of HCC were significantly older, mainly males, had higher alpha-fetoprotein (AFP) levels before DAA and at SVR24, higher Fib-4 levels, and higher LS0, 24, and 48 than those without a history of HCC. Age (p = 0.013) and AFP at SVR24 (p = 0.036) correlated with occurrence. LS48 (p = 0.043) correlated with recurrence. Conclusions: Predictive factors differed between HCC occurrence and recurrence after SVR by DAA in HCV patients. High recurrence rates were due to fibrosis in the liver being more advanced in patients with than in those without a history of HCC. Age and AFP at SVR24 were identified as predictive factors of HCC occurrence and LS48 of HCC recurrence.