Clinical trial NCT03665766: Effect of Cyclosporine A Versus Tacrolimus on Response to Antiviral Therapy After Hepatitis C Genotype -4 Recurrence Post Liver Transplantation
Official title: The Effect of Cyclosporine A Versus Tacrolimus on the Response to Antiviral Treatment After HCV Genotype -4 Recurrence in Recipients of Living Donor Liver Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Transplantation
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2018-09-11
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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) , group two received the direct antiviral agent (DAA) sofosbuvir plus RBV and group three received daclatasvir, sofosbuvir (other DAAs) plus RBV each group was further subdivided according to primary immunosuppression (CsA or Tac)

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.


Eligibility criteria: 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

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 .

Primary outcomes:
measure: sustained virological response
timeFrame: 24 weeks for group I and 12 weeks for group II and III
Secondary outcomes:
Other outcomes:
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