A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients

Gary L. Davis, David R. Nelson, Norah Terrault, Timothy L. Pruett, Thomas D. Schiano, Courtney V. Fletcher, Christine V. Sapan, Laura N. Riser, Yufeng Li, Richard J. Whitley, John W. Grann

Research output: Contribution to journalArticle

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Abstract

Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

Original languageEnglish (US)
Pages (from-to)941-949
Number of pages9
JournalLiver Transplantation
Volume11
Issue number8
DOIs
StatePublished - Aug 1 2005

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Pharmacokinetics
Chronic Hepatitis C
Safety
Liver Transplantation
Liver
Immunoglobulins
Hepatitis C Antibodies
Transplants
Hepatitis B
Serum
Alanine Transaminase
Hepacivirus
Antiviral Agents
Half-Life
Transplant Recipients
human hepatitis C immune globulin
Fibrosis
Transplantation
RNA
Biopsy

ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

Cite this

A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. / Davis, Gary L.; Nelson, David R.; Terrault, Norah; Pruett, Timothy L.; Schiano, Thomas D.; Fletcher, Courtney V.; Sapan, Christine V.; Riser, Laura N.; Li, Yufeng; Whitley, Richard J.; Grann, John W.

In: Liver Transplantation, Vol. 11, No. 8, 01.08.2005, p. 941-949.

Research output: Contribution to journalArticle

Davis, GL, Nelson, DR, Terrault, N, Pruett, TL, Schiano, TD, Fletcher, CV, Sapan, CV, Riser, LN, Li, Y, Whitley, RJ & Grann, JW 2005, 'A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients', Liver Transplantation, vol. 11, no. 8, pp. 941-949. https://doi.org/10.1002/lt.20405
Davis, Gary L. ; Nelson, David R. ; Terrault, Norah ; Pruett, Timothy L. ; Schiano, Thomas D. ; Fletcher, Courtney V. ; Sapan, Christine V. ; Riser, Laura N. ; Li, Yufeng ; Whitley, Richard J. ; Grann, John W. / A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. In: Liver Transplantation. 2005 ; Vol. 11, No. 8. pp. 941-949.
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