Posttransplant antiviral therapy in recipients with evidence of
biochemical and histological recurrent disease, usually 6 months
after LT, is the mainstay of management. Although a high
number of transplant centers use antiviral therapy, the
treatment is not standardized and is still associated with low
rates of SVR, less than those reported in the non-transplant
setting. The main reasons include high VL post-LT, a higher
frequency of genotype 1 patients, poor tolerability of treatment
after LT, and need for frequent dose reductions.
The combination of PegIFN/RBV is the treatment of choice also
in transplant recipients. The SVR associated with PegIFN/RBV
therapy in predominantly genotype 1 infected populations has
been reported to range from 12% to as high as 50% (Gonzalez
2010). A recent extensive review of 19 prospective and
retrospective clinical studies describing antiviral therapy with
PegIFN/RBV in this population reported a mean SVR of 30.2%
(Berenguer 2008). End of treatment virologic response (EoTR)
was 42.2% (range 17-68%), indicating that relapse was a major
factor in the low SVR rates. Biochemical responses were
registered in 54.8% and histological endpoints were judged to be
too heterogeneous in definition and assessment to provide a
summary estimate. However, it was noted that histological
improvements were generally confined to treated patients who
achieve SVR. Fibrosis has been shown to progress significantly
more in nonresponders to antiviral therapy. Even in the absence
of virological response, the rate of progression of fibrosis was
86 | Hepatitis C Treatment
significantly slowed in patients treated for more than 6 months
(Walter 2009). Using long-term maintenance antiviral therapy
has recently been shown to increase the probability of
biochemical and histological responses, regardless of the timing
of the HCV recurrence (de Martin 2010).
Achievement of SVR in the setting of recurrent HCV following
LT has a major impact on long-term outcomes, including
improved graft and patient survival. Identifying patients with a
greater likelihood of achieving SVR is an important
consideration in the selection of potential treatment candidates
and is a key factor in developing strategies for optimizing
response to therapy.
Predictors of response to therapy identified in different studies
(Terrault 2008, Selzner 2009, Gonzalez 2010, Fukuhara 2010)
were
– Non-1 HCV genotype
– Absence of prior antiviral therapy
– Donor age
– Pretreatment necroinflammatory activity and fibrosis stage
– Concomitant cyclosporine use
– Course completion (the rule of 80/80/80, see chapter 1)
– Low pretreatment HCV RNA (<1 million IU/ml)
– IL28B polymorphism in recipient and donor tissues
– RVR or EVR – that hold the highest predictive values of SVR.
Undetectable VL at 24 weeks of therapy was also noted to
confer a high predictive value (92%) for SVR and prolonged
treatment protocol was suggested in these LT recipients.
biochemical and histological recurrent disease, usually 6 months
after LT, is the mainstay of management. Although a high
number of transplant centers use antiviral therapy, the
treatment is not standardized and is still associated with low
rates of SVR, less than those reported in the non-transplant
setting. The main reasons include high VL post-LT, a higher
frequency of genotype 1 patients, poor tolerability of treatment
after LT, and need for frequent dose reductions.
The combination of PegIFN/RBV is the treatment of choice also
in transplant recipients. The SVR associated with PegIFN/RBV
therapy in predominantly genotype 1 infected populations has
been reported to range from 12% to as high as 50% (Gonzalez
2010). A recent extensive review of 19 prospective and
retrospective clinical studies describing antiviral therapy with
PegIFN/RBV in this population reported a mean SVR of 30.2%
(Berenguer 2008). End of treatment virologic response (EoTR)
was 42.2% (range 17-68%), indicating that relapse was a major
factor in the low SVR rates. Biochemical responses were
registered in 54.8% and histological endpoints were judged to be
too heterogeneous in definition and assessment to provide a
summary estimate. However, it was noted that histological
improvements were generally confined to treated patients who
achieve SVR. Fibrosis has been shown to progress significantly
more in nonresponders to antiviral therapy. Even in the absence
of virological response, the rate of progression of fibrosis was
86 | Hepatitis C Treatment
significantly slowed in patients treated for more than 6 months
(Walter 2009). Using long-term maintenance antiviral therapy
has recently been shown to increase the probability of
biochemical and histological responses, regardless of the timing
of the HCV recurrence (de Martin 2010).
Achievement of SVR in the setting of recurrent HCV following
LT has a major impact on long-term outcomes, including
improved graft and patient survival. Identifying patients with a
greater likelihood of achieving SVR is an important
consideration in the selection of potential treatment candidates
and is a key factor in developing strategies for optimizing
response to therapy.
Predictors of response to therapy identified in different studies
(Terrault 2008, Selzner 2009, Gonzalez 2010, Fukuhara 2010)
were
– Non-1 HCV genotype
– Absence of prior antiviral therapy
– Donor age
– Pretreatment necroinflammatory activity and fibrosis stage
– Concomitant cyclosporine use
– Course completion (the rule of 80/80/80, see chapter 1)
– Low pretreatment HCV RNA (<1 million IU/ml)
– IL28B polymorphism in recipient and donor tissues
– RVR or EVR – that hold the highest predictive values of SVR.
Undetectable VL at 24 weeks of therapy was also noted to
confer a high predictive value (92%) for SVR and prolonged
treatment protocol was suggested in these LT recipients.
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