Serum Alfa Fetoprotein versusNitric Oxide after Direct - Acting Antiviral Therapy to Predict Incident Hepatocellular Carcinoma in Chronic Hepatitis C Patients

Background: In the last decade, a great success was achieved in eradication of hepatitis C virus (HCV) infection owing to treatment with direct-acting antiviral agents (DAAs). However, an increased incidenceof hepatocellular carcinoma (HCC) in treated patients was also noticed. In this study, a suggested link between altered serum nitric oxide (sNO) level after DAAs therapy and new development of HCC was investigatedas compared to serum alfa fetoprotein (AFP). Methods: We prospectively followed 180treatment naïve chronic hepatitis C (CHC) patients while receiving 12 weeks course ofDAAs therapy (sofosbuvir/daclatasvir±ribavirin)and for two years thereafter.In addition to routine laboratory evaluation, serum AFP and sNO levels were assessed before and after treatment. At the end of the study, all participants were classified into HCC group (who developed new HCC during study period) and non-HCC group.Results: Throughout the study, incident HCC was diagnosed in 7.8% of all participants (14/180). HCC developed only in cirrhotic patients, being more with advanced than early cirrhosis (P<0.001).As compared to baseline levels, serum AFP and sNOrise significantly after DAAs therapy (P=0.005 and P<0.001, respectively).Post treatment levels of AFP and sNO were significantly higher in HCC group than non-HCC group (P<0.001 for both).The only independent predictor of incident HCC after DAAs therapy was elevated sNO (P<0.001).Using receiver operating characteristic statistics, the sensitivity and specificity of post-DAAs sNO (100% and 99.4%, respectively), at a cut-off level ≥ 290 μmol/L, for HCC prediction (area under the curve=0.998, P<0.001), were much higher than that of AFP. Conclusion:Marked increase ofsNO level in CHC patients after DAAs therapy significantly predictsnew HCC development, which is predisposed by underlying cirrhosis.