Clinical outcome of hypogammaglobulinaemic patients following outbreak of acute hepatitis C: 2 year follow up

Abstract

SUMMARYIn 1994, an outbreak of hepatitis C virus (HCV) infection, genotype 1a, occurred in 30 hypogammaglobulinaemic patients in the UK from one batch of contaminated anti-HCV screened intravenous immunoglobulin. This study aimed to study prospectively the outcome of HCV in hypogammaglobulinaemic patients, and to assess the response to early treatment with interferon-alpha, 6 million units three times weekly for 6 months. Data were collected using standardized questionnaires. Five patients with secondary hypogammaglobulinaemia due to lymphoid malignancy were not treated and all have died of their primary malignancy. Of 25 patients with primary hypogammaglobulinaemia, one resolved HCV infection before treatment, 17 commenced on treatment, and seven declined or treatment was contra-indicated. Thirteen of 17 patients completed therapy and seven (54%) have a sustained response (normal transaminases, negative serum HCV RNA) at 6 and 12 months after treatment. Two of the 12 patients with primary hypogammaglobulinaemia, who were not treated or failed to complete treatment, have cleared the virus. Liver biopsy was performed in patients not clearing HCV and was abnormal in all. Four patients developed liver failure within 2 years, of whom three have died and one has been successfully transplanted. In conclusion, HCV can cause rapid severe liver disease in hypogammaglobulinaemic patients. Early treatment with high-dose interferon-alpha results in a high clearance of HCV.

Adaptive Immunity to the Hepatitis C Virus

“…Direct evidence supporting involvement of the humoral immune response in control of HCV replication or resolution of infection is sparse. Spontaneous resolution without seroconversion has been observed in chimpanzees (Cooper et al , 1999) and humans (Christie et al , 1997; Post et al , 2004), including some with primary antibody deficiency (Christie et al , 1997). Although the number of subjects with hypogammaglubulinemia who permanently cleared viremia was small, this study provided support for the concept that anti-HCV antibodies are not necessarily required for a successful infection outcome (Christie et al , 1997).…”

“…Spontaneous resolution without seroconversion has been observed in chimpanzees (Cooper et al , 1999) and humans (Christie et al , 1997; Post et al , 2004), including some with primary antibody deficiency (Christie et al , 1997). Although the number of subjects with hypogammaglubulinemia who permanently cleared viremia was small, this study provided support for the concept that anti-HCV antibodies are not necessarily required for a successful infection outcome (Christie et al , 1997). On the other hand, passive transfer of serum containing HCV immunoglobulins to chimpanzees substantially delayed, but did not prevent, replication of the virus upon challenge (Krawczynski et al , 1996), suggesting that antibodies can alter the trajectory of infection.…”

Hepatic Dysfunction in a Population of Antibody–Deficient Patients: Prevalence, Aetiology and Outcome of PCR Screening for Hepatitis C and G Viruses

“…Data from a cohort of UK patients who became HCV–infected after receiving a contaminated batch of immunoglobulin showed a high rate of infection and poor outcome was not infrequent. Further data from this group indicating a satisfactory outcome in many of the patients treated promptly with interferon–α therapy emphasises the importance of frequent monitoring and early detection of hepatic dysfunction [16]. A strict monitoring policy such as ours reveals a number of patients with abnormal liver function tests.…”

Designing an HCV vaccine: a unique convergence of prevention and therapy?

“…Antibody-mediated depletion of CD8+ T cells in a second group of naturally immune animals caused prolonged infection after rechallenge[38]. These findings, and the observation that some HCV infections resolve in the absence of an antibody response[39], supported a bold hypothesis that vaccination to prime T cell immunity might be sufficient to prevent HCV persistence. This concept was tested by Folgori, Nicosia, and colleagues at Okairos Corporation (now Glaxo Smith Kline).…”