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

✍ Scribed by 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. Gnann Jr.

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 149 KB
• Volume: 11
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.20405

✦ Synopsis

Collaborative Antiviral Study Group

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 highdose 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. (Liver Transpl 2005;11:941-949.)

H epatitis C virus (HCV) infection affects more than 1% of the world population and about 4 million individuals in the United States. 1,2 Chronic infection usually results in liver disease, which is often insidiously progressive. Cirrhosis develops in about 20% of cases and these patients are then at risk for developing hepatic failure or hepatocellular carcinoma. 3 These complications of chronic hepatitis C are the most common indications for liver transplantation in the United States. 4 Unfortunately, recurrence of HCV infection after transplantation is almost universal, and reinfection may result in hepatitis, hepatic fibrosis, and decreased survival. 5 Although interferonbased antiviral therapy is useful in some patients with recurrent hepatitis, 6,7 there is generally no effective way to prevent posttransplantation recurrence of infection in the graft or modify the outcome of the disease.

Immune globulin containing virus-specific antibodies has been shown to be an effective treatment in several viral diseases and is particularly useful in preventing recurrent hepatitis B after liver transplantation. [8][9][10] Immune globulin enriched in antibody to HCV is able