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.

Course and outcome of hepatitis C

“…Patients who develop chronic HCV infection usually have no other evidence of immunologic deficiency. Conversely, some patients with marked immunodeficiency can, nevertheless, recover from acute hepatitis C. 56,57 The actual chronicity rate of acute HCV infection is not well established. There have been no large-scale prospective studies of unselected patients with acute HCV infection of suitable size and duration to document the actual frequency of chronicity.…”

Acute Hepatitis C

“…Of particular interest are studies of hepatitis C outcomes in antibody-deficient patients. Although numbers are limited, it is notable that spontaneous resolution has been reported in HCV-infected agammaglobulinemic children, [40][41][42] providing strong evidence that control of HCV can occur independently of antibodies. Indeed, combining these small studies, disease termination occurred in approximately 15% of antibody-deficient children, a proportion tantalizingly similar to that anticipated in the general population.…”

Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia

“…Undoubtedly other co-morbidities including alcohol consumption, intra-venous drug abuse and co-infection with hepatitis B (HBV) adversely impact on the clinical course also. It is noteworthy that Italian patients appear to follow a more benign course following HCV infection than other populations [13,16] , suggesting a role of HCV viral load and genotype in the genesis of liver disease.…”

“…Some reports suggest a rapidly progressive course with poor patient outcomes [8,11] , while others demonstrate the more usual, slowly progressive course, at least in the short term [12,13] . A less aggressive clinical course has been observed in patients with XLA compared with those with combined variable immunodeficiency [14] , although this remains a source of debate [15] .…”