Direct acting antiviral therapy of chronic hepatitis C may affect the progression of dysplastic nodules to hepatocellular carcinoma: A pilot study

In the era of interferon free direct acting antiviral (DAA) drug therapy for chronic hepatitis C(CHC), one of the goals of treatment is to reduce the occurrence of liver cirrhosis related complications through viral clearance, the most important of which is hepatocellular carcinoma (HCC). This goal was based on the effect of the older therapy of Pegylated Interferon and Ribavirin which resulted in reduction of HCC occurrence in compensated cirrhotic patients who achieved sustained virologic response (SVR). The rate of HCC occurrence was strongly decreased after SVR but not abolished with incidence of HCC ranging from 0.4 to 2%.1 Confirming this role for DAA needs longer time of follow up, especially for cirrhotic patients who have achieved SVR. Recently, some studies reported increased aggressiveness and rates of HCC recurrence in HCC patients who cleared HCV with DAA after achieving complete response to resection or local ablation of the tumor.2 Others concluded that cirrhotic patients treated by DAA are not at increased risk of developing (de novo) HCC compared to untreated patients.3 HCC development in CHC cirrhotic patients may pass through two different pathways.4,5 One is the multistep carcinogenesis process,5,6 progressing from regeneration or cirrhotic nodule (RN) to low grade dysplastic nodule (LGDN), high grade dysplastic nodule (HGDN) then HCC.4 The other pathways is the de novo carcinogenesis.