Prophylaxis of hepatitis C with intramuscular immunoglobulin - Clinical and economic appraisal

Hepatitis C virus (HCV) affects millions of individuals worldwide. In most cases, HCV infection progresses to chronic liver disease and, subsequently, to liver cirrhosis and hepatocellular carcinoma. HCV is transmitted by the parenteral route, for example by transfusion of blood or blood products, i njection during drug abuse, etc., and by the inapparent parenteral route (p enetration of the virus through difficult-to-identify microlesions present on the skin or mucosae), for example, sexual exposure or household exposure to infected contacts, etc. The cost of chronic hepatitis C and its sequela e is high in both financial and human terms. At present, only anti-HCV screening of blood/organ/tissue donors and univer sal precautions for the prevention of blood-borne infections are recommende d for HCV prevention. Before the discovery of the main aetiological agent o f non-A, non-B hepatitis (HCV), several randomised controlled clinical tria ls demonstrated that standard intramuscular immunoglobulin exerted a preven tive effect on post-transfusional and sexual and/or horizontal transmission of non-A, non-B hepatitis. When serological tests for HCV infection became available, bimonthly inoculation of standard unscreened intramuscular immu noglobulin (prepared from plasma pools containing about 2% of anti-HCV-posi tive units) was demonstrated to significantly prevent sexually transmitted HCV infection. The immunoglobulin used contained high titres of anti-HCV ne utralising antibodies (anti-E2 neutralisation of binding assay), whereas cu rrently available commercial screened immunoglobulin (prepared from anti-HC V-negative blood units) did not. This finding suggested that anti-HCV neutr alising antibodies are concentrated only in anti-HCV-positive units (which are currently discarded). Thus, anti-HCV hyperimmune globulin (HCIg) can be produced only from anti-HCV-positive units. The neutralising titre can be increased by the exclusive use of units with higher titres of neutralising antibodies. Unlike other hyperimmune globulins, which are produced from a l imited number of selected donors, HCIg should be produced from a large numb er of units so as to contain neutralising antibodies to the different HCV s trains. HCIg will have a number of advantages: (i) it is easy to produce an d inexpensive: (ii) it has a long half-life, allowing infrequent administra tion: (iii) new additional viral inactivation procedures have been introduc ed to eradicate transmission of infection, and (iv) it may be possible to n eutralise all the emerging HCV strains. HCIg could be used in all individua ls at risk of HCV infection (sexual partners, haemodialysis patients, etc), in preventing reinfection of transplanted livers, and perhaps also in the treatment of chronic hepatitis C, alone or associated with other drugs.