The clinical spectrum of AEs is similar to the non-transplant
setting (see chapter 1). Dose reductions are frequent and drug
discontinuation rates are higher than in nontransplant patients.
A major limitation of antiviral therapy is tolerability,
particularly with respect to the hematologic AEs of PegIFN/RBV.
In a recent Cochrane review, up to 87.5% of patients required a
dose reduction and up to 42.9% of patients stopped treatment
Management of recurrent HCV infection following liver transplantation | 87
because of AEs or because of patient's choice to stop it
(Gurusamy 2010). Cytopenias, mood disturbances, and acute
cellular rejection are the most common reasons for dose
reduction or discontinuation (Terrault 2008). The use of growth
factors is required to manage cytopenias (anemia and
neutropenia) in up to 50% of patients, and thus to improve
tolerability. However, there is not enough evidence to support
improvement of SVR with concomitant use of Filgastrim and/or
erythropoietin. Anemia is a common side effect especially in
older LT recipients and with a low BMI (Saab 2007). RBV toxicity
can be of concern in LT recipients with renal dysfunction. Lower
initial RBV dosing, increasing as tolerated, or dosing based on a
nomogram that incorporates renal function (creatinine
clearance) is highly recommended (Watt 2009).
Acute cellular rejection (ACR) and chronic ductopenic rejection
are immune-mediated complications unique to the posttransplant
setting. Acute and chronic rejections are infrequent
complications of antiviral therapy often associated with
concomitant low or negative serum HCV RNA. The reported
incidence of ACR during interferon based therapy ranges from 0
to 35%. It is to be noted that the incidence of ACR in HCV positive
LT recipients treated with combination antiviral therapy for
HCV recurrence does not seem to be higher than that observed
in non treated HCV positive LT recipients (Seltzner 2010).
An autoimmune-like hepatitis (de novo autoimmune hepatitis)
has been reported in LT recipients treated with PegIFN/RBV for
recurrent hepatitis C. In general, these patients have no history
of autoimmune disease, and HCV RNA is undetectable at the time
of the secondary rise in liver enzymes. In HCV infected patients,
it remains controversial whether these cases represent a true
autoimmune (alloimmune) process, as opposed to an atypical
manifestation of recurrent disease or of acute or chronic
allograft rejection. Histologic findings are an essential part in
the differential diagnosis between these entities. Any flare in
liver enzymes in patients treated with antiviral therapy,
particularly in those with undetectable HCV RNA, should raise
88 | Hepatitis C Treatment
the suspicion of these complications and warrant the
performance of a liver biopsy.
setting (see chapter 1). Dose reductions are frequent and drug
discontinuation rates are higher than in nontransplant patients.
A major limitation of antiviral therapy is tolerability,
particularly with respect to the hematologic AEs of PegIFN/RBV.
In a recent Cochrane review, up to 87.5% of patients required a
dose reduction and up to 42.9% of patients stopped treatment
Management of recurrent HCV infection following liver transplantation | 87
because of AEs or because of patient's choice to stop it
(Gurusamy 2010). Cytopenias, mood disturbances, and acute
cellular rejection are the most common reasons for dose
reduction or discontinuation (Terrault 2008). The use of growth
factors is required to manage cytopenias (anemia and
neutropenia) in up to 50% of patients, and thus to improve
tolerability. However, there is not enough evidence to support
improvement of SVR with concomitant use of Filgastrim and/or
erythropoietin. Anemia is a common side effect especially in
older LT recipients and with a low BMI (Saab 2007). RBV toxicity
can be of concern in LT recipients with renal dysfunction. Lower
initial RBV dosing, increasing as tolerated, or dosing based on a
nomogram that incorporates renal function (creatinine
clearance) is highly recommended (Watt 2009).
Acute cellular rejection (ACR) and chronic ductopenic rejection
are immune-mediated complications unique to the posttransplant
setting. Acute and chronic rejections are infrequent
complications of antiviral therapy often associated with
concomitant low or negative serum HCV RNA. The reported
incidence of ACR during interferon based therapy ranges from 0
to 35%. It is to be noted that the incidence of ACR in HCV positive
LT recipients treated with combination antiviral therapy for
HCV recurrence does not seem to be higher than that observed
in non treated HCV positive LT recipients (Seltzner 2010).
An autoimmune-like hepatitis (de novo autoimmune hepatitis)
has been reported in LT recipients treated with PegIFN/RBV for
recurrent hepatitis C. In general, these patients have no history
of autoimmune disease, and HCV RNA is undetectable at the time
of the secondary rise in liver enzymes. In HCV infected patients,
it remains controversial whether these cases represent a true
autoimmune (alloimmune) process, as opposed to an atypical
manifestation of recurrent disease or of acute or chronic
allograft rejection. Histologic findings are an essential part in
the differential diagnosis between these entities. Any flare in
liver enzymes in patients treated with antiviral therapy,
particularly in those with undetectable HCV RNA, should raise
88 | Hepatitis C Treatment
the suspicion of these complications and warrant the
performance of a liver biopsy.
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