Preemptive Therapy with Combination Peg-Intron and Ribavirin in Liver Transplant Recipients with Hepatitis C Is Poorly Tolerated and of Small Benefit

The management protocols for recurrent HCV are diverse and the issues are complex, including the effectiveness of preemptive therapy. The current study  presents results of a retrospective review of liver transplant recipients receiving preemptive therapy of pegylated alfa-2b interferon (Peg-Intron) and ribavirin within 4 months of transplant.

The objectives of the study were to determine if preemptive therapy with peginterferon alfa-2b and ribavirin for recurrent HCV post liver transplantation is safe and effective.

All recipients were started on combination pegylated alfa-2b interferon (0.5mcg/kg) and ribavirin (200-400 mg/d) therapy within 16 weeks of liver transplantation.

Dose escalation was as follows: increase in pegylated alfa-2b interferon 0.5mcg/kg every 4 weeks until 1.5mcg/kg and ribavirin 200 mg/d every 4 weeks until 800-1000 mg/d. The therapy was followed for at least 48 weeks of therapy.

The diagnosis of HCV recurrence was determined by histopathologic findings with inflammation along with viral recurrence using COBAS AMPLICOR Hepatitis C virus Test, version 2.0 and COBAS AMPLICOR HCV MONITOR TEST-version 2.0 assays. Histology was graded and staged according to the Batts and Ludwig classification.

The diagnosis of recurrent hepatitis was based on the presence of portal lymphocytic infiltrates, interface hepatitis, and lobular necroinflammatory injury in the absence of other findings that could indicated a different pathology.

Results

14 transplant recipients were included in the study: female 5(36%), males 9 (64%) mean age (50yrs), mean time from OLT was 6.7 weeks, Caucasians 8 (57%) and Hispanics 6 (43%).

Three patients remained serologically negative for HCV 3/15 (20%) for a 48 week period and 3 patients dropped their serum HCV PCR 2 logs (20%). The remaining 8 patients were viremic throughout the 48 week period.

The side effects included clinical depression 6 (43%) of which treatment was stopped in 2 while 2 improved to near baseline with SSRI therapy, thrombocytopenia (< 50K) 3 (20%), 1 (7%) require treatment cessation, neutropenia 3(20%) all responding to filgastrim.

Serum ALT normalized in 5/14 (36%). 4 patients remained on therapy for 48 consecutive weeks.

One death was noted as a result of fungal sepsis, and one patient experienced HAT. 

SVR was attained in 2/14 (14%), both tissue HCV PCR was negative at time of 48 week biopsy.

Conclusion

According to the authors, “These results show that preemptive therapy was poorly tolerated while benefiting only a small portion of our cohort (20%).”

06/07/04

Reference
G W Neff and others. Preemptive Therapy with Combination Pegylated Interferon and Ribavirin in Liver Transplant Recipients with Hepatitis C Virus. Abstract 1153 (poster). Digestive Disease Week. May 15-20, 2004. New Orleans, LA.