A high rate of hepatitis C virus (HCV) infection has been reported [1] in Norwegian patients with primary hypogammaglobulinemia after treatment with intravenous immunoglobulin. The preparation involved was Gammonativ (KabiVitrim), known to have been previously contaminated with a non-A, non-B hepatitis virus [2]. Similar cases have been reported in the United States with Gammagard (Baxter Health Care, Glendale, California) and possibly Polygam (American Red Cross, Washington, D.C.) [3]. We describe a patient with hypogammaglobulinemia who developed acute HCV infection after receiving Venoglobulin-I (Alpha Therapeutic Corporation, Los Angeles, California).

A 60-year-old woman with hypogammaglobulinemia had been receiving immunoglobulin infusions at 3-week intervals (Sandoglobulin, Sandoz Pharmaceuticals, East Hanover, New Jersey) for 10 years, except for an 8-month period in 1991 when it was withheld to assess the need for continued therapy. Because of recurrent respiratory infections, she began receiving Venoglobulin-I. In February 1994, she presented with 4 weeks of nausea, fatigue, and abdominal pain. She had received Venoglobulin-I infusions on 2 December 1993, 23 December 1993, and 13 January 1994. She reported no alcohol or intravenous drug use, receipt of other blood products, or recent sexual intercourse. Physical examination was unremarkable, but laboratory testing showed a serum aspartate aminotransferase level of 1055 IU/L, an alanine aminotransferase level of 1219 IU/L, an alkaline phosphatase level of 166 U/L, and a bilirubin level of 0.8 mg/dL. All of these levels had been normal 1 month previously. Results of testing for viral infection (including anti-HCV antibody) were negative. However, serum HCV-RNA levels were positive in high concentration when a semi-quantitative assay was used [4].

The patient was treated with 6 months of interferon-, 3 MU three times per week, with normalization of her aminotransferase levels; HCV-RNA levels became negative 10 weeks after she started treatment. However, evidence of biochemical and virologic relapse was noted 3 weeks after interferon- was stopped, and a liver biopsy specimen showed mild chronic hepatitis with recent injury. Reinstitution of interferon- therapy led to prompt biochemical and virologic remission. She remains negative for anti-HCV antibody approximately 1 year after onset of disease.

Venoglobulin-S includes a solvent and detergent treatment phase to inactivate HCV. Venoglobulin-I (a polyvalent immunoglobulin preparation) does not have a specific viral inactivation method, but the basic manufacturing process removes between 4 and 6 logs of hepatitis C [5]. No previous cases of HCV transmission have been reported with either preparation (Personal communication. Alpha Therapeutic Corporation). It is extremely unlikely that this patient acquired HCV infection from any other source.

Regardless of the preparation used, all patients who receive intravenous immunoglobulin should have routine monitoring with liver function tests and should be monitored closely for immediate and long-term adverse effects. The assay for HCV-RNA is required to evaluate these patients for HCV infection. As our report shows, screening such patients with anti-HCV antibody testing is inadequate.