Protocol for management of Hepatitis C after OLT

Background:

1)Chronic hepatitis C is the most common indication for liver transplantation in the United States.

2)Recurrent hepatitis C after liver transplantation is an important cause of morbidity and mortality.

3)Death, graft loss, or cirrhosis can develop in up to one-third of HCV infected OLT recipients by five years post-transplantation.

4)Histological benefits have been noted with antiviral therapy for recurrent HCV.

5)Patients who obtain an SVR have a lower incidence of cirrhosis during follow-up than do nonresponders.

6)Treatment of recurrent HCV after OLT is associated with reduced risk of graft failure.

Patients who have undergone OLT for cirrhosis due to HCV should be considered for antiviral treatment with peginterferon +/- ribavirin.

Inclusion Criteria:

1)HCV identified by PCR

2)Histological evidence of recurrence (fibrosis stage 1) on annual liver biopsy or biopsy performed when clinically indicated.

Exclusion Criteria:

1)Histological evidence of allograft rejection

2)Previous failed antiviral therapy after liver transplantation

3)Platelet count <75,000 cells/mm3

4)Hemoglobin < 10 g/dL

5)Uncontrolled depression or history of suicide attempts/ideation

6)Abnormal thyroid function

7)History of significant cardiac disease

8)Pregnancy or consideration of pregnancy

Treatment Regimen:

1)Typical treatment duration 48 weeks for genotype 1, 24 weeks for genotype 2/3. To be guided by viral kinetics – slow responders may require longer duration of antiviral therapy.

2)Dosages of peginterferon

  1. 180 mcg/week sq for peginterferon 2a
  2. 1.5 mcg/kg/week for peginterferon 2b
  3. Half-dose if ANC falls to less than 750 cells/mm3 (despite use of GM-CSF) or if platelet count falls to <50,000 cells/mm3
  4. Peginterferon dosing should be discontinued for 2 weeks if ANC decreases to <500 cells/mm3 or platelet count falls to <25,000 cells/mm3.

3)Initial ribavirin dosages administered in divided doses daily

  1. 1200 mg/day if CrCl >60 ml/min and weight >75 kg
  2. 1000 mg/day if CrCl >60 ml/min and weight <75 kg
  3. 800 mg/day for genotype 2 or 3
  4. If CrCl 30-60 ml/min, initiate ribavirin at 400 mg/day in divided doses and increase by 200 mg/day every 2 weeks as tolerated.
  5. Peginterferon monotherapy if CrCl <30 ml/min.

4)If hemoglobin decreases to <10 g/dL, consider initiation of erythropoietin or decrease dose of ribavirin by 200 mg/day.

5)Labs to be monitored weekly for the first month, and then monthly thereafter:

  1. CBC with differential (every 2 weeks if interferon/ribavirin dose being adjusted)
  2. BMP (every 2 weeks if interferon/ribavirin dose being adjusted)
  3. Hepatic panel
  4. HCV viral level at week 4, week 12 (treatment discontinued if viral level has not decreased by 2log), week 24 (treatment discontinued if viral level not negative by week 24), week 48, and 6 months after treatment discontinued.
  5. Clinic follow up at week 4, week 12, week 24, week 36, week 48

6)Treatment discontinued if symptomatic anemia that does not respond to treatment, major depression, allograft rejection or induction of alloimmune hepatitis, or clinical decompensation

References:

1)Carrion JA, Navasa M, Garcia-Retortillo M, et al. Efficacy of Antiviral Therapy on Hepatitis C Recurrence After Liver Transplantation: A Randomized Controlled Study. Gastroenterology 2007:132:1746-56

2)Angelico M, Petrolati A, Lionetti R, et al. A randomized study on Peg-interferon alfa-2a with our without ribavirin in liver transplant recipients with recurrent hepatitis C. J Hepatol 2007:46:1009-17

3)Veldt BJ, Poterucha JJ, Watt KDS, et al. Impact of Pegylated Interferon and Ribavirin Treatment on Graft Survival in Liver Transplant Patients with Recurrent Hepatitis C Infection. Am J Transplantation 2008;8:2426-33