Category: Federal Forum Posters
Purpose: Direct-acting antiviral agents (DAAs) have been presented as a safe and effective alternative in the solid organ transplant population. Drug interactions between DAAs and immunosuppressive therapy are well established, which allows an adequate management in clinical practice. However, since some of these drugs such as tacrolimus are metabolized mainly by the liver, it is necessary to know the impact that the improvement in liver function could have on their blood levels.
Purpose: To describe the impact of Hepatitis C virus (HCV) infection clearance after DAAs treatment on tacrolimus blood levels in kidney transplant recipients.
Methods: Study design: Single-centre, retrospective study.
Inclusion criteria: Adult kidney transplant recipients receiving tacrolimus as part of maintenance immunosuppressive therapy, who had prior HCV infection and had obtained sustained virologic response 24 weeks after treatment (SVR24) with a DAA-based regimen between April 2015 to June 2018.
Demographic data (age, sex) and response to treatment with DAAs (SVR24) were collected. Liver function (liver fibrosis degree, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and bilirubin), renal function (MDRD-4), tacrolimus dose and blood levels were analyzed before and 12 weeks after the end of DAA treatment.
To measure our endpoint, tacrolimus level/dose ratio (expressed as ng/mL per mg/day) were compared before and 12 weeks after the end of treatment.
Results: We identified 5 male patients with a median age of 52 years (36-73).
Before HCV treatment, patients received an average of 2 mg per day (0.5- 5 mg per day) of tacrolimus and had a median blood level of 5.8 ng/mL (IQR: 3.8 -8.45 ng/mL).The most common HCV genotype was 1b (3/5; 60%). One patient had HCV genotype 1a and one had genotype 4. All patients were treatment naïve (100%) when initiating the DAA regimen. Two patients were coinfected with HIV.
All achieved SVR24 after the end of the 12 week treatment with: Dasabuvir + Ombitasvir / Paritaprevir / Ritonavir (2/5) or Sofosbuvir / Ledipasvir (3/5).
At week 12 after HCV treatment, all liver funcionality tests showed a significant improvement from baseline, except in the genotype 4 patient, with no significant changes in renal function. This difference was considered statistically significant for the fibro Scan decline (44%), ALT decline (67%: p<0.005) and for the AST decline (54.0%: p<0.05).
In these patients, a decrease in the tacrolimus level / dose ratio of tacrolimus was observed 12 weeks after treatment with DAAs: 188 to 108, 138 to 82, 570 to 215 and 531 to 221.
Conclusion: In conclusion, the use of DAAs for the treatment of HCV is expanding due to its efficacy and safety in kidney transplant recipients. In view of the potential recovery effect of liver after achieving a SVR24 in patients with chronic HCV infection, we hardly recommend a close monitoring of tacrolimus blood levels immediately after treatment with DAAs. Otherwise, an underdosing of the immunosuppression could go unnoticed and suppose a potential risk of graft rejection
Sara IbaÃ±ez Garcia– Clinical Pharmacist, HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON, Madrid, Madrid, Spain