Immunosuppression in HCV-positive liver-transplant recipients

Abstract

HCV (+) transplant recipients present unique challenges. Over the years, there has been progress but there is clearly no consensus regarding the optimal immunosuppressive medications or drug regimens; however, there continues to be advancements in the management of patients with HCV. Though current studies do not provide clear evidence as to optimal immunosuppression, they do identify questions ideally addressed by large, randomized controlled trials.

Is Minimal, [Almost] Steroid-Free Immunosuppression a Safe Approach in Adult Liver Transplantation? Long-term Outcome of a Prospective, Double Blind, Placebo-Controlled, Randomized, Investigator-Driven Study

“…[3][4][5][6][7][8] The frequent insufficient sample size, heterogeneous trial design, lack of relevant RCTs, and most of all absence of well documented, long-term follow-up do not allow firm conclusions to be made in relation to which IS strategy to follow. Despite this, several messages can be taken to the clinical arena: (a) the superiority of CNIs as the mainstay of IS 3 ; (b) and of TAC in terms of overall and rejection-free survival rates 24 ; (c) inadequacy of CNI-free induction IS due to high ACR rates 23 ; (d) misleading of conclusions in most studies focusing on the superiority of several drug combinations in relation to steroid and CNI sparing as CNI dosing in the control arms is usually higher than advocated in the sparse, well-designed minimization RCTs 23,[25][26][27] ; (e) the necessity for individualized IS in HCV-infected and cancer patients [28][29][30] ; (f) interference of heavy IS with the active process of tolerance induction 21,22,31 ; and last but not least (g) the inability to make firm conclusions about the "optimal" lS regimen in absence of well-documented long-term pathologic follow-up. It is indeed well known that normal liver function tests do not necessarily correlate with normal biopsy and viceversa.…”

“…22 These findings indicate that the evolution of HCV reinfection is mainly determined by the IS itself rather than by different induction and maintenance IS regimen. 28,29 A recent study indicates that HCV recipients may benefit from an IS regimen that includes low-dose steroids and azathioprine. 29 Our study underlines the importance of routine liver biopsies as part of long-term follow-up of liver recipients.…”

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

“…78 mTOR inhibitors, such as sirolimus and everolimus, have anti-proliferative, anti-inflammatory, and possible antiviral effects, which may translate to a lower rate of HCV disease evolving to cirrhosis. 79,80 A retrospective analysis of 141 HCV+ LT recipients demonstrated that a sirolimus-based regimen did not significantly delay the time to develop severe recurrence of HCV after LT. 79 In contrast, in a prospective cohort of 67 patients (39 received sirolimus, 28 received calcineurin inhibitors), the sirolimus group had significantly lower HCV-RNA levels and increased survival. 81 In addition, two independent retrospective studies (N51274 and 313) have demonstrated with sirolimus a reduction in the degree of fibrosis and the rate of progression in HCV+ LT recipients.…”

Role of mTOR inhibitors for the control of viral infection in solid organ transplant recipients

“…Results from literature review are shown in Table . All the studies analyzed the development of fibrosis, a surrogate marker for the defined outcome (time to the diagnosis of fibrosing cholestatic hepatitis or cirrhosis).…”