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Effect of Cyclosporine A Versus Tacrolimus on Response to Antiviral Therapy After Hepatitis C Genotype -4 Recurrence Post Liver Transplantation

Completed
Conditions
Liver Transplantation
Interventions
Drug: Cycloserine,Tacrolimus
Registration Number
NCT03665766
Lead Sponsor
Ain Shams University
Brief Summary

Background and Aim: The immunosuppression influence on the response to antiviral therapy (AVT) for recurrent hepatitis C virus (HCV) infection in liver transplant (LT) recipients remains controversial, especially for the rarely investigated genotype 4.This study aims to compare the effects of the two widely used calcineurin inhibitors(CNIs)(Cyclosporine A (CsA) and tacrolimus (Tac)) on the therapeutic response to different AVT regimens. Method: In126 living donor liver transplant (LDLT) recipients with recurrent HCV infection, participants were categorized to three groups according to AVT. Group one received pegylated interferon (Peg IFN-α 2a) and ribavirin (RBV) (n= 44), group two received the direct antiviral agent (DAA) sofosbuvir plus RBV (n=52) and group three received daclatasvir, sofosbuvir (other DAAs) plus RBV(n=30) each group was further subdivided according to primary immunosuppression (CsA or Tac). The sustained virological response (SVR) and relapse rates were considered the primary therapeutic outcomes of AVT. The virological response guided therapy end points for AVT were considered the secondary outcomes.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
126
Inclusion Criteria

group(I):participants received Peg IFN-α 2a and RBV therapy who fulfilled the following inclusion criteria:

  • Age between 18 and 65 years ;
  • elevated aminotransferase levels (ALT and AST)
  • detectable HCV RNA by polymerase chain reaction (PCR)
  • liver biopsy results consistent with HCV recurrence using the Metavir scoring system (Metavir ≥A1F1)
  • For group II and III:
  • age between 18 and 75 years
  • detectable HCV RNA by PCR
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Exclusion Criteria

group I

  • if they were younger than 18 years or older than 65 years or had one of the following criteria
  • alcoholic
  • poorly controlled autoimmune disease
  • significant cardiac disease
  • suicidal ideation
  • a history of suicide attempt
  • major psychosis
  • serum creatinine ˃3 mg/dl
  • thyroid dysfunction
  • combined kidney-liver transplantation
  • were currently pregnant or planning pregnancy.

Group II and III:

  • younger than 18 years or older than 75 years
  • total bilirubin (T.Bil) >3 mg/dl
  • serum albumin< 2.8 mg/dl
  • international normalized ratio ≥1.7
  • Platelet count < 5000/mm3
  • HCC, except 4 weeks after intervention with no evidence of activity using computed tomography or magnetic resonance imaging
  • extra hepatic malignancy except after two years of disease free-interval
  • uncontrolled diabetes evidenced by glycated haemoglobin >9%
  • were pregnant .
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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
IFN group received CyclosporineCycloserine,TacrolimusLiving donor liver transplantation recipients with recurrent HCV received Peg IFN-α 2a and RBV as antiviral therapy and Cyclosporine A as primary immunosuppression ,this was routinely taken not as intervention according to local practice
IFN group received tacrolimusCycloserine,TacrolimusLiving donor liver transplantation recipients with recurrent HCV received Peg IFN-α 2a and RBV as antiviral therapy and Tacrolimus as primary immunosuppression ,this was routinely taken not as interventing according to local practice
Sof plus Rbv group received CyclosporineCycloserine,TacrolimusLiving donor liver transplantation recipients with recurrent HCV received sofosbuvir and RBV as antiviral therapy and Cyclosporine as primary immunosuppression,this was routinely taken not as intervention according to local practice
Sof plus Rbv received tacrolimusCycloserine,TacrolimusLiving donor liver transplantation recipients with recurrent HCV received sofosbuvir and RBV as antiviral therapy and Tacrolimus as primary immunosuppression,this was routinely taken not as intervention according to local practice
Sof,dac pus ribavirin received cyclosporineCycloserine,TacrolimusLiving donor liver transplantation recipients with recurrent HCV received daclatasvir, sofosbuvir and RBV as antiviral therapy and Cyclosporine as primary immunosuppression,this was routinely taken not as intervention according to local practice
sof,dac plus rbv received tacrolimusCycloserine,TacrolimusLiving donor liver transplantation recipients with recurrent HCV received daclatasvir, sofosbuvir and RBV as antiviral therapy and Tacrolimus as primary immunosuppression,this was routinely taken not as intervention according to local practice
Primary Outcome Measures
NameTimeMethod
sustained virological response24 weeks for group I and 12 weeks for group II and III

a negative serum HCV RNA

Secondary Outcome Measures
NameTimeMethod
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