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Abstract
Background: Direct-acting antiviral agents therapy is considered a breakthrough in hepatology due to high rates of sustained virologic response in all patients including those with decompensated cirrhosis. However, impact of Direct-acting antiviral agents-induced sustained virologic response on hepatocellular carcinoma development remains conflicting.
 Aims: This study aimed at evaluating the change in circulating levels of vascular endothelial growth factor and transforming growth factor-β1, the main angiogenic factors involved in hepatocarcinogenesis process, in cirrhotic patients achieved sustained virologic response after Direct-acting antiviral agents therapy.
 Study Design: This was a prospective, single-center, cohort study.
 Place and Duration of Study: Patients were recruited from the outpatient clinic of National Liver Institute, which considered a tertiary referral center in Menoufia University, Egypt (September 2018 to February 2019).
 Methodology: Forty-five decompensated cirrhotic hepatitis C virus infected patients with no history of hepatocellular carcinoma participated in the study. All patients received 60mg oral daclatasvir and 400mg oral sofosbuvir once daily for 12 or 24 weeks with or without ribavirin. Serum levels of vascular endothelial growth factor and transforming growth factor-β1 were measured at baseline and 12 weeks after the end of therapy.
 Results: The median serum levels of vascular endothelial growth factor showed a non-statistically significant increase (from 1123 ng/L to 1269 ng/L, P = 0.126). But, transforming growth factor-β1 median serum levels exhibited a non-statistically significant reduction (from 13.22 ng/ml to 12.44 ng/ml, P = 0.163) 12 weeks after treatment.
 Conclusion: Our findings show direct-acting antiviral agents therapy do not affect vascular endothelial growth factor and transforming growth factor-β1 serum levels. But, a larger scale prospective cohort study on an extended follow-up period is recommended.
Highlights
Direct-acting antiviral agents therapy is considered a breakthrough in hepatology due to high rates of sustained virologic response in all patients including those with decompensated cirrhosis
This study aimed at evaluating the change in circulating levels of vascular endothelial growth factor and transforming growth factor-β1, the main angiogenic factors involved in hepatocarcinogenesis process, in cirrhotic patients achieved sustained virologic response after Direct-acting antiviral agents therapy
Our findings show direct-acting antiviral agents therapy do not affect vascular endothelial growth factor and transforming growth factor-β1 serum levels
Summary
Chronic hepatitis C virus (HCV) infection is the prime causation of liver cirrhosis and hepatocellular carcinoma (HCC) [1] HCV accounts for about 27% of cirrhotic cases and about 25% of HCC cases worldwide, and over 350000 people die each year from hepatitis Crelated liver diseases [2,3]. Oral combination of daclatasvir (DCV) an HCV nonstructural protein 5A (NS5A) replication complex inhibitor and sofosbuvir (SOF) a nucleotide analogue HCV nonstructural protein 5B (NS5B) polymerase inhibitor has powerful antiviral action and wide genotypic coverage achieving extremely elevated sustained virological response (SVR) rates nearly close to 100% in both treatment-naïve and treatmentexperienced patients. These impressive results are expected to modulate the disease epidemiology and aid in achieving the goal of eliminating HCV infection in Egypt [8]. Place and Duration of Study: Patients were recruited from the outpatient clinic of National Liver Institute, which considered a tertiary referral center in Menoufia University, Egypt (September 2018 to February 2019).
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