Vascular Endothelial growth factor A in HCV infected patients before and after treatment with DAAS and its possible relation to HCC development

Abstract

With the introduction of Direct acting antiviral agents (DAAS) ,the rate of sustained virological response (SVR) in the treatment of HCV infection has radically improve to over 90% which has abeneficial effect on progression of liver diease . However ,adebate on the impact of DAAS on the development of HCC is going on. It has been reported in some recent studies that DAAS administration induce an early increase in serum VEGF and change in inflammatory pattern coinciding with HCV clearance . This may alter the balance between inflammatory and anti inflammatory processes and modify the antitumour survillence of the host.Whether such change in serum level of VEGF can explain HCC occurrence in our Egyptian cirrhotic patients after DAAS treatment is questionable .This study was conducted on 25 patients with HCV related cirrhosis eligible for antiviral treatment by DAAS and 25HCC patients diagnosed by serum AFP and triphasic CT abdomen ,all of them were HCV positive from January 2018 to july 2019. Serum VEGF was determind in plasma of both groups and after starting treatment by sofosubuvir 400mg plus daclatasvir 60mg for three months in HCV patient group (one month post treatment and three months post treatment) . We found in this study that serum VEGF was significantly higher in HCC patients (479.69_167.5 mg/ml )than HCV before starting treatment (208.7_115.4 mg/ml) (p value < 0.001) . Similarly serum AFP level in HCC group (368.6-146.5 mg /ml) was significantly higher than HCV patient group (4.83-1.98mg/ml) (p value < 0.001). Serum VEGF decreased after one month of DAAS treatment from (208.7_115.4 mg/ml) to (62.64_56.27 mg/ml) (p value less than 0.001), then further decreased to (48.56-22.92mg/ml) at three months post treatment. We found also that serum VEGF decreased in 10 patients of HCC patients who underwent two locoregional treatment by TACE compared to those 15 patients without intervention (295.8-108.25 versus 602.28-116.57 mg/ml) (p value < 0.001). Sensitivity of VEGF as adiagnostic marker for HCC was 88% and specificity was 88% and it decreased significantly with treatment by DAAS and with intenrvention by TACE in HCC patient reflecting its diagnostic and prognostic value particularly if compined with AFP in HCV infected patients . However we found that change in serum VEGF in HCV patients treated with DAAS in this study cannot explain risk of HCC after treatment by DAAS . However there is alimitation for this study, that is the relatively small number of patients and the need to study changes in other angiogenic and antiangiogenic factors to explore the role of angiogensis and proinflammatory pathway in carcinogensis in HCV infected patients.