Page 82 - The Flying Publisher Guide to Hepatitis C Treatment

82 | Hepatitis C Treatment

tacrolimus and cyclosporine with respect to their impact on
histologically diagnosed HCV recurrence and graft or patient
survival (Iacob 2007, Berenguer 2007). Cyclosporine has a strong
in vitro suppressive effect on HCV replication (Watashi 2003).
Several clinical although relatively small studies suggested a
higher sustained virologic response (SVR) in HCV LT patients
receiving cyclosporine and interferon therapy.
The cornerstone of immunosuppressive agents, the
corticosteroids, slowly tapered off over a long time, may prevent
progression to severe forms of recurrent disease (Iacob 2007,
Brillanti 2002). In contrast, the boluses of methylprednisolone
(MP) used for acute rejection episodes were deleterious to the
HCV-related graft survival. Outcome of HCV-positive patients
who received multiple pulses of MP is significantly worse than
that in patients with a single pulse therapy (Bahra 2005). High
levels of viremia can determine an HCV-cytopathic mechanism
involved in the allograft injury. Currently, steroid-free
immunosuppression regimens are preferred in HCV recipients.
Actual data for mycophenolate mofetil (MMF), a morpholino
ester prodrug of mycophenolic acid (MPA), favor its use in
recurrent hepatitis C. MPA is a selective, noncompetitive,
reversible inhibitor of inosine monophosphate dehydrogenase
(IMPD), a key enzyme in the biosynthetic pathway of the guanine
nucleotides. It is also a potent inhibitor of both B and T cell
proliferation. MMF in combination with CNI taper showed a
positive effect on fibrosis progression, graft inflammation and
ALT levels (Lake 2009, Iacob 2007). Less data are available for
azathioprine, but its inclusion in the maintenance regimen was
associated with survival advantage.
The potential antifibrotic and antiviral benefit of mTOR
(mammalian target of rapamycin) inhibitors after LT in HCV
positive patients awaits further investigation in prospective
randomized controlled trials. Sirolimus, a macrolide isolated
from Streptomyces hygroscopius reduces TGF-β and procollagen,
inhibits hepatic stellate cell proliferation and may have an
inhibitory action on HCV replication through phosphorylation of