Impact of Antiviral Therapy on Gastroesophageal Varices.

Study Overview
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Brief Summary
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Hepatitis C virus (HCV) chronic infection affects 200 million people worldwide. HCV antiviral treatment has evolved rapidly since 2011. The use of pegylated interferon (PEG-INF) with ribavirin (RBV) has supposed high serious adverse events (SAEs) and low efficacy, especially in patients with cirrhosis. The introduction of 1st generation protease inhibitors (PIs) in genotype-1 (GT1) HCV, such as boceprevir (BOC) and telaprevir (TVR), improved the efficacy but increased the SAEs. Currently, interferon-free direct-acting antivirals (IF-DAAs) achieve great effectiveness with minimum SAEs. However, studies evaluating efficacy and safety of DAAs in cirrhotic patients are limited in real clinical practice. The aim of our study is to evaluate in HCV-cirrhotic patients the efficacy and safety of 3 treatment strategies (PEG-IFN/RBV, PEG-IFN/RBV/PIs, and IF-DAAs) in routine practice according to European guidelines from 2010 to 2015. The secondary aim is to evaluate the impact of sustained virological response on gastroesophageal varices (GOV).

Official Title
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Efficacy and Safety of Interferon Based Therapy and Interferon-free Direct-acting Antivirals in Cirrhotic Patients With Hepatitis C. Impact of Antiviral Therapy on Gastroesophageal Varices.

Conditions
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Chronic Hepatitis C, Cirrhosis

Intervention / Treatment
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* Drug: Pegylated interferon alfa-2a + Ribavirin
* Drug: Pegylated interferon alfa-2a + Ribavirin + Boceprevir
* Drug: Pegylated interferon alfa-2a + Ribavirin +Telaprevir
* Drug: Ledipasvir/Sofosbuvir
* Drug: Ombitasvir/paritaprevir/ritonavir+Dasabuvir
* Drug: Daclatasvir+Sofosbuvir
* Drug: Simeprevir+Sofosbuvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Signed informed consent. Chronic hepatitis C (anti-HCV antibodies and detectable HCV-RNA). Liver cirrhosis (transient elastography ≥ 14 kPa). Baseline upper gastrointestinal endoscopy to assess gastroesophageal varices Exclusion Criteria: Negative to provide signed informed consent. Negative to perform gastrointestinal endoscopy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PEG/RBV<br>Pegylated interferon alfa-2a 180 microg/week plus ribavirin 800-1200 mg during 48 weeks according to routine practice and European Guidelines (EASL recommendations 2011) | Drug: Pegylated interferon alfa-2a + Ribavirin<br> <br> |
| PEG/RBV+BOC or TVR<br>Boceprevir 800 mg/8h or Telaprevir 750 mg/8h plus Pegylated interferon alfa-2a 180 microg/week plus ribavirin 800-1200 mg during 48 weeks according to routine practice and European Guidelines (EASL recommendations 2014) | Drug: Pegylated interferon alfa-2a + Ribavirin + Boceprevir<br> <br> Drug: Pegylated interferon alfa-2a + Ribavirin +Telaprevir<br> <br> |
| IF-DAAs<br>Interferon-free direct-acting antiviral combinations according to routine practice and European Guidelines (EASL recommendations 2015) Fixed-dose combination of sofosbuvir (400 mg) and ledipasvir (90 mg) daily +/- ribavirin 12-24 weeks Fixed-dose combination of ombitasvir (75 mg), paritaprevir (12.5 mg) and ritonavir (50 mg) in one single tablet (two tablets once daily) and dasabuvir (250 mg) (one tablet twice daily) with ribavirin 800-1200 mg 12 weeks (Genotype 1b) or 24 weeks (genotype 1a) Daily sofosbuvir (400 mg) and daily simeprevir (150 mg) +/- ribavirin 12-24 weeks Daily sofosbuvir (400 mg) and daily daclatasvir (60 mg) +/- ribavirin 12-24 weeks | Drug: Ledipasvir/Sofosbuvir<br> <br> Drug: Ombitasvir/paritaprevir/ritonavir+Dasabuvir<br> <br> Drug: Daclatasvir+Sofosbuvir<br> <br> Drug: Simeprevir+Sofosbuvir<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sustained virological response (SVR) | undetectable HCV viral load 12 weeks after the end of antiviral treatment in each cohort of antiviral treatment | 12 weeks after treatment completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with gastroesophageal varices | Number of patients with GOV before and 12-24 weeks after treatment completion in patients with or without SVR | gastroesophageal varices (GOV) before antiviral treatment and 12-24 weeks after treatment completion |