The main goals of treating cirrhotic patients with antiviral
therapy are to prevent the complications of the disease, to halt
disease progression or allow for the regression of cirrhosis, and
to attain sustained viral clearance in order to prevent
reinfection in the graft in patients undergoing LT.
SVR in patients with Child-Pugh (CP) class A cirrhosis has
improved from 5% with interferon monotherapy to 50% with
pegylated interferon alfa (PegIFN) + ribavirin (RBV) in genotype
1 (Everson 2005).
The safety of combination therapy in cirrhotics is a major
concern. Bone marrow suppression by administration of either
standard or PegIFN alfa leads to significant decrease in all three
lineages of the hematopoietic system (Iacobellis 2008). However,
erythropoietic agents are effective in treating anemia,
preventing RBV dose reduction, improving patients‘ quality of
life, but the effect on SVR is not fully elucidated. Granulocyte
colony-stimulating factor is effective in raising ANC; however,
neutropenic HCV-infected patients on combination treatment
may not experience increased bacterial infections. Eltrombopag,
a new oral thrombopoietin mimetic, may allow combination
treatment in patients with cirrhosis and thrombocytopenia.
Antiviral therapy is commonly deferred in cirrhotics with signs
of liver decompensation, due to even more compelling concerns
over treatment-induced side effects (up to 60%).
There are several studies reporting experience with interferonbased
therapy in pre-transplant patients aiming to prevent
reinfection of the new graft (Alsatie 2007). The largest study
(Everson 2005) included 124 patients with an average CP score of
7.4 and a mean MELD (Model for End Stage Liver Disease – the
currently used allocation system, introduced in 2002 in USA in
order to prioritize patients on the waiting list) score of 11, who
received a low-accelerating-dose regimen. An SVR of 24% was
84 | Hepatitis C Treatment
achieved and 12 of 15 patients who were HCV RNA-negative
before LT remained HCV RNA-negative ≥6 months
postoperatively. The following predictors of response in these
studies were identified: non-1 genotype, CTP class A (genotype 1
only), ability to tolerate full dose and duration of treatment,
lower pretreatment VL, a VL decrease ≥2 log10 at week 4 of
treatment (Alsatie 2007). Premature discontinuation of the
therapy due to side effects was reported in 13-30% and dose
reductions were more frequent.
On the basis of available data, prophylactic antiviral therapy in
this setting to prevent recurrent HCV infection post-LT has a
limited role and may be associated with serious AEs.
Pretransplant therapy, using a low-accelerating dose regimen, is
an important treatment strategy but is applicable to selected
patients only. Prophylactic antiviral therapy should not be
considered in those with high MELD score (≥20) or CTP class B or
C. It is to be noted that up to two-thirds of patients who become
HCV RNA–negative on treatment will be HCV-free posttransplantation.
therapy are to prevent the complications of the disease, to halt
disease progression or allow for the regression of cirrhosis, and
to attain sustained viral clearance in order to prevent
reinfection in the graft in patients undergoing LT.
SVR in patients with Child-Pugh (CP) class A cirrhosis has
improved from 5% with interferon monotherapy to 50% with
pegylated interferon alfa (PegIFN) + ribavirin (RBV) in genotype
1 (Everson 2005).
The safety of combination therapy in cirrhotics is a major
concern. Bone marrow suppression by administration of either
standard or PegIFN alfa leads to significant decrease in all three
lineages of the hematopoietic system (Iacobellis 2008). However,
erythropoietic agents are effective in treating anemia,
preventing RBV dose reduction, improving patients‘ quality of
life, but the effect on SVR is not fully elucidated. Granulocyte
colony-stimulating factor is effective in raising ANC; however,
neutropenic HCV-infected patients on combination treatment
may not experience increased bacterial infections. Eltrombopag,
a new oral thrombopoietin mimetic, may allow combination
treatment in patients with cirrhosis and thrombocytopenia.
Antiviral therapy is commonly deferred in cirrhotics with signs
of liver decompensation, due to even more compelling concerns
over treatment-induced side effects (up to 60%).
There are several studies reporting experience with interferonbased
therapy in pre-transplant patients aiming to prevent
reinfection of the new graft (Alsatie 2007). The largest study
(Everson 2005) included 124 patients with an average CP score of
7.4 and a mean MELD (Model for End Stage Liver Disease – the
currently used allocation system, introduced in 2002 in USA in
order to prioritize patients on the waiting list) score of 11, who
received a low-accelerating-dose regimen. An SVR of 24% was
84 | Hepatitis C Treatment
achieved and 12 of 15 patients who were HCV RNA-negative
before LT remained HCV RNA-negative ≥6 months
postoperatively. The following predictors of response in these
studies were identified: non-1 genotype, CTP class A (genotype 1
only), ability to tolerate full dose and duration of treatment,
lower pretreatment VL, a VL decrease ≥2 log10 at week 4 of
treatment (Alsatie 2007). Premature discontinuation of the
therapy due to side effects was reported in 13-30% and dose
reductions were more frequent.
On the basis of available data, prophylactic antiviral therapy in
this setting to prevent recurrent HCV infection post-LT has a
limited role and may be associated with serious AEs.
Pretransplant therapy, using a low-accelerating dose regimen, is
an important treatment strategy but is applicable to selected
patients only. Prophylactic antiviral therapy should not be
considered in those with high MELD score (≥20) or CTP class B or
C. It is to be noted that up to two-thirds of patients who become
HCV RNA–negative on treatment will be HCV-free posttransplantation.
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