Improved Efficacy and Tolerability in Treating Post-Transplant HCV Utilizing an Escalating Regimen of Pegylated Interferon Alfa-2a (Pegasys) and Ribavirin with Hematopoietic Growth Factors

Initial data suggests that therapy for recurrent hepatitis C virus (HCV) post orthotopic liver transplantation (OLT) with interferon and ribavirin is poorly tolerated with at least a 30% early discontinuation rate due to side effects.

In this study, HCV Patients (pts.) post OLT with documented histological recurrence were prospectively commenced on a standardized escalating protocol of pegylated interferon alfa-2a (Pegasys) and ribavirin at doses of 90 mcg/week and 7 mg/kg BID respectively for the first month, to a full dose (180 mcg/week and 14 mg/kg BID) by the third month.

Response to therapy was assessed as "on treatment" virological response (OTR) at 6 months.

Anemia was defined as hemoglobin (Hb) < 12g/dL, with neutropenia defined as a total white cell count (WCC) of < 1.5 x 103 u/L. Below this threshold hematopoietic growth factors (EPO and G-CSF) were used to maintain hematological parameters.

Results

Twenty five pts. were treated for recurrent HCV post OLT. There were no early discontinuations of therapy. Two pts. who had recurrent decompensated cirrhosis underwent a trial of antiviral therapy but subsequently died.

The mean stage of fibrosis prior to therapy was 1.64 +/- 1.29. The majority of pts. were genotype 1.

Thirteen (52%) demonstrated OTR at 6 months after a mean duration of 2.57 months of therapy; 12/19 (63%) with stage 0-2 fibrosis and only 1/6 (17%) with stage 3-4 fibrosis had OTR (p = 0.22).

Twenty one (84%) received EPO for symptomatic anemia and 11 (44%) were treated with G-CSF for neutropenia. The mean WCC at the start of therapy was 5.02 x103 u/L (range 2.4-9.5), the nadir on therapy was 2.09 x 103 u/L (range 1.0-5.4), with a mean drop in WCC of 2.94. This occurred at a mean of 3.96 months into therapy.

The mean platelet count at the start of therapy was 134 (range 87-253), the nadir on therapy was 79 (range 26-187), with a mean drop in platelet count of 55. Four patients (15%) developed significant depression requiring antidepressants. No patients developed infection or bleeding with 1 documented episode of histological rejection.

Conclusions

The authors conclude, “Pegylated interferon alfa-2a and ribavirin are effective and well tolerated for post transplant HCV using an escalating dose regimen. Our data demonstrates that aggressive use of hematopoietic growth factors is essential to prevent early discontinuation, achieve adequate dosing and improve response rates of therapy.”

06/07/04

Reference
N Kontorinis and others. Improved Efficacy and Tolerability in Treating Post-Transplant HCV Utilizing an Escalating Regimen of Pegylated Interferon alfa-2a and Ribavirin with Hematopoietic Growth Factors: A Prospective Study. Abstract 45 (oral). Digestive Disease Week. May 15-20, 2004. New Orleans, LA.