Curing Hepatitis C in Liver Transplant Recipients Is Associated with Changes in Immunosuppressant Use

Abstract

Background and Aims: All-oral interferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients. The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR). Methods: We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with all-oral direct acting agents. Results: We identified 52 liver LT treated recipients who achieved a SVR. The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75, 65). Most recipients received tacrolimus (TAC) for their immunosuppressant regimen. After achieving SVR, there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05). However, there was a statistically significant decrease in daily dose of TAC adjusted per weight, serum levels of TAC, and the product of glomerular filtration rate and TAC. No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted. Conclusions: Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine. LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.

Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature

“…Indeed, numerous studies have described a higher drug exposure of the two most commonly used immunosuppressants, tacrolimus and cyclosporine A, in patients with hepatitis and especially in those with viremia ( Tuncer et al, 2000 ; Latorre et al, 2002 ; Wolffenbüttel et al, 2004 ). Moreover, when HCV is treated, CYP activities appear to return to baseline levels in several studies ( McHorse et al, 1975 ; van den Berg et al, 2001 ; Kugelmas et al, 2003 ; Ueda et al, 2015 ; Kawaoka et al, 2016 ; Saab et al, 2016 ; Raschzok et al, 2016 ; Ueda and Uemoto, 2016 ; Smolders et al, 2017 ). Indeed, through concentration of tacrolimus decreased after initiation of HCV treatment, such as sofosbuvir, daclatasvir, asunaprevir, simeprivir, ribavirin and interferon, administered alone or in combination, and it required a dosage increase ( Kawaoka et al, 2016 ; Raschzok et al, 2016 ; Saab et al, 2016 ; Smolders et al, 2017 ).…”

“…Moreover, when HCV is treated, CYP activities appear to return to baseline levels in several studies ( McHorse et al, 1975 ; van den Berg et al, 2001 ; Kugelmas et al, 2003 ; Ueda et al, 2015 ; Kawaoka et al, 2016 ; Saab et al, 2016 ; Raschzok et al, 2016 ; Ueda and Uemoto, 2016 ; Smolders et al, 2017 ). Indeed, through concentration of tacrolimus decreased after initiation of HCV treatment, such as sofosbuvir, daclatasvir, asunaprevir, simeprivir, ribavirin and interferon, administered alone or in combination, and it required a dosage increase ( Kawaoka et al, 2016 ; Raschzok et al, 2016 ; Saab et al, 2016 ; Smolders et al, 2017 ). Subgroups were identified, such as patients not responding to interferon with higher CYP3A downregulation related to higher levels of circulating cytokines, confirming that CYP modulation is proportional to intensity of inflammation ( Morcos et al, 2013 ).…”

The Reliability of Fibro-test in Staging Orthotopic Liver Transplant Recipients with Recurrent Hepatitis C

“…[15][16][17]20 The issues of drug-drug interactions, varying degrees of concomitant renal insufficiency, and rarely acute rejection also come into consideration in the post-transplant setting, making the treatment of RHC more challenging. 6,17,21 What is more, sustained virological response rates appear to be lower in simultaneous liver-kidney transplant recipients. 17 As such, until a universally accepted, streamlined, 100% effective and caveat-free regimen is found to treat RHC in liver recipients, there will be a need to monitor disease progression in those few who fail or do not tolerate our current options.…”

“…[1][2][3] The advent of direct-acting antivirals (DAAs) dramatically changed the landscape of HCV treatment, with safe and effective regimens that have high cure rates leading to significantly improved outcomes in the post-OLT setting 4,5 Still, treatment of recurrent hepatitis C (RHC) in liver transplant recipients may pose a challenge. 6 As such, there remains the necessity to periodically restage the relatively few patients who either fail or are unable to tolerate DAA treatment.…”

The Islet Confidential: Recent Trends and Perspectives in Pancreatic Islet Transplantation

“…This study recommends post transplantation strategies such as transarterial embolization and ethanol injection to combat this dilemma. In addition to HEV, HCV infections also are implicated in graft rejection in liver transplantation [23].…”