Clinical management of renal transplant patients with hepatitis C virus infection treated with cyclosporine or tacrolimus

Latorre, Alejandro Tomas; Morales, Ever; González, E. Redondo; Herrero, Juan Carlos; Ortiz, M; Sierra, Prado; Domínguez‐Gil, Beatriz; Torres, Antonia; Múñoz, María Teresa; Andrés, Amado; Manzanares, C; Morales, José

doi:10.1016/s0041-1345(01)02678-1

Cited by 11 publications

(10 citation statements)

References 3 publications

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“…Latorre et al reported doses and levels of ciclosporin (n ¼ 12) and tacrolimus (n ¼ 14) in 26 renal transplant patients with HCV infection. 5 At 1 year, the levels of tacrolimus and ciclosporin were similar, but the doses required in HCV patients were significantly lower by one-third compared to patients without HCV. In a large study which randomized renal transplant recipients to ciclosporin or tacrolimus at transplantation, the doses and levels were reported in 30 HCV patients.…”

Section: Introductionmentioning

confidence: 90%

Effect of hepatitis C infection on tacrolimus doses and blood levels in liver transplantation recipients

Trotter¹,

Osborne²,

Heller³

et al. 2005

Aliment Pharmacol Ther

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SUMMARYBackground: In our cohort of patients with hepatitis-C virus, which is the most common indication for liver transplantation, we have noted higher relative blood levels of tacrolimus compared to patients without hepatitis-C virus. Aim: To verify this observation and determine its clinical significance, we performed a comparison of doses and blood levels of tacrolimus in hepatitis-C virus and nonhepatitis-C virus liver transplantation recipients. Methods: Tacrolimus dose and trough level, as well as mean alanine aminotransferase, for all patients transplanted at our center with a deceased donor between 1/1995 and 12/1999 with hepatitis-C virus were recorded at monthly intervals during the first 24 months following transplantation and compared to patients without hepatitis-C virus.

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Section: Introductionmentioning

confidence: 90%

Effect of hepatitis C infection on tacrolimus doses and blood levels in liver transplantation recipients

Trotter¹,

Osborne²,

Heller³

et al. 2005

Aliment Pharmacol Ther

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“…In liver disease and hepatic inflammation, CYP expression decreases which may reduce the metabolism of many medications. During HCV treatment, viral load declines and hepatic inflammation improves, leading to normalization of CYP expression …”

Section: Introductionmentioning

confidence: 99%

“…Tacrolimus (TAC), the backbone of immunosuppression in LT, is a substrate of CYP3A4/5. In the transplant population, normalization of CYP expression that occurs following HCV treatment may lead to an increase in TAC metabolism and sequential subtherapeutic concentrations, and increase the risk of graft rejection . The majority of large randomized controlled trials evaluating HCV DAA therapy post‐LT do not specifically report on immunosuppression management during and following HCV DAA therapy .…”

Section: Introductionmentioning

confidence: 99%

“…During HCV treatment, viral load declines and hepatic inflammation improves, leading to normalization of CYP expression. 12,13 Tacrolimus (TAC), the backbone of immunosuppression in LT, is a substrate of CYP3A4/5. In the transplant population, normalization of CYP expression that occurs following HCV treatment may lead to an increase in TAC metabolism and sequential subtherapeutic concentrations, and increase the risk of graft rejection.…”

Section: Introductionmentioning

confidence: 99%

“…In the transplant population, normalization of CYP expression that occurs following HCV treatment may lead to an increase in TAC metabolism and sequential subtherapeutic concentrations, and increase the risk of graft rejection. 12,13 The majority of large randomized controlled trials evaluating HCV DAA therapy post-LT do not specifically report on immunosuppression management during and following HCV DAA therapy. [14][15][16][17][18] However, there are a small number of retrospective reports that observed a decline in TAC whole blood concentrations in LT recipients during treatment with DAAs.…”

Section: Introductionmentioning

confidence: 99%

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Impact of direct‐acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients

Bixby

Fitzgerald

Leek

et al. 2019

Transplant Infectious Dis

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Introduction Direct‐acting antivirals (DAAs) have transformed hepatitis C virus (HCV) management post‐liver transplant. As HCV clears during DAA treatment, hepatic metabolism improves, resulting in decreased tacrolimus concentrations that may require dose adjustment. The purpose of this study was to determine appropriate management of immunosuppression in liver transplant recipients during and following treatment of HCV. Methods This study was a single‐center retrospective analysis of 71 liver transplant recipients who were treated for HCV with DAAs. The primary outcome was change in dose‐normalized tacrolimus concentrations from the start of DAA treatment to 12 weeks following therapy. Results The mean change in log‐transformed dose‐normalized tacrolimus concentrations was a reduction of 0.43 ng/mL/mg (95% CI; 0.26‐0.60, P < 0.0001). The greatest decrease occurred in the first 4 weeks of treatment, after which levels stabilized. The overall mean tacrolimus concentration was 4.8 ng/mL (±2.5). Two patients (3%) developed acute cellular rejection and two patients (3%) had graft loss and died. Conclusion From the start of treatment to 12 weeks post‐DAA therapy, liver transplant recipients experienced a significant decrease in dose‐normalized tacrolimus concentrations. In conclusion, close monitoring of tacrolimus concentrations is warranted during and following treatment with DAAs, as dose increases may be indicated in order to maintain therapeutic concentrations to prevent graft rejection.

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Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail

Lenoir

Daali

Rollason

et al. 2021

Clin Pharma and Therapeutics

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Cytochromes P450 (CYP) are subject to important interindividual variability in their activity due to genetic and environmental factors and some diseases. Limited human data support the idea that inflammation downregulates CYP activities. Our study aimed to evaluate the impact of orthopedic surgery (acute inflammation model) on the activity of six human CYP. This prospective observational study was conducted in 30 patients who underwent elective hip surgery at the Geneva University Hospitals in Switzerland. The Geneva phenotyping cocktail containing caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, and midazolam as probe drugs respectively assessing CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A activities was administered orally before surgery, day 1 (D1) and 3 (D3) postsurgery and at discharge. Capillary blood samples were collected 2 hours after cocktail intake to assess metabolic ratios (MRs). Serum inflammatory markers (CRP, IL-6, IL-1β, TNF-α, and IFN-γ) were also measured in blood. CYP1A2 MRs decreased by 53% (P < 0.0001) between baseline and the nadir at D1. CYP2C19 and CYP3A activities (MRs) decreased by 57% (P = 0.0002) and 61% (P < 0.0001), respectively, with the nadir at D3. CYP2B6 and CYP2C9 MRs increased by 120% (P < 0.0001) and 79% (P = 0.018), respectively, and peaked at D1. Surgery did not have a significant impact on CYP2D6 MR. Hip surgery was a good acute inflammation model as CRP, IL-6, and TNF-α peak levels were reached between D1 and day 2 (D2). Acute inflammation modulated CYP activity in an isoform-specific manner, with different magnitudes and kinetics. Acute inflammation may thus have a clinically relevant impact on the pharmacokinetics of these CYP substrates.

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Clinical management of renal transplant patients with hepatitis C virus infection treated with cyclosporine or tacrolimus

Cited by 11 publications

References 3 publications

Effect of hepatitis C infection on tacrolimus doses and blood levels in liver transplantation recipients

Effect of hepatitis C infection on tacrolimus doses and blood levels in liver transplantation recipients

Impact of direct‐acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients

Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail

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