Most of the women with HCV infection 17 years after receiving HCV-contaminated anti-D immune globulin had evidence of slight or moderate hepatic inflammation on liver biopsy, about half had fibrosis, and 2 percent had probable or definite cirrhosis.

The genomic sequences of viruses that are highly mutable and cause chronic infection tend to diverge over time. We report that these changes represent both immune-driven selection and, in the absence of immune pressure, reversion toward an ancestral consensus. Sequence changes in hepatitis C virus (HCV) structural and nonstructural genes were studied in a cohort of women accidentally infected with HCV in a rare common-source outbreak. We compared sequences present in serum obtained 18–22 yr after infection to sequences present in the shared inoculum and found that HCV evolved along a distinct path in each woman. Amino acid substitutions in known epitopes were directed away from consensus in persons having the HLA allele associated with that epitope (immune selection), and toward consensus in those lacking the allele (reversion). These data suggest that vaccines for genetically diverse viruses may be more effective if they represent consensus sequence, rather than a human isolate.

Hepatitis C virus (HCV) infection is the main cause of non-A, non-B hepatitis. 1-5 HCV consists of a heterogeneous mix of isolates defined by genotype, each of which is further classified into subtypes. 6,7 A number of factors have been considered in terms of their potential to predict the outcome of the disease. These include age of infection, viral typesubtype, quasispecies, viral load, and mode of infection. [8][9][10][11][12][13] Clinical heterogeneity in disease progression may reflect viral heterogeneity and variations in host response. 14-17 The human leukocyte antigen (HLA) has been shown to influence host response to infection. [18][19][20][21][22] Although HLA class II genes have shown associations with viral clearance or persistence of the HCV these findings are not uniform. [23][24][25][26][27][28] In addition, direct comparisons between studies is often difficult because of heterogeneity of ethnic background, viral genotype, phenotype frequencies of individual alleles between populations, gender, and duration of disease. To avoid heterogeneity of risk factors and confounding variables in viral type/subtype we studied a unique cohort of individuals all infected by anti-D contaminated from a single source of HCV 1b. The patients were of similar ethnogeographic background and had an absence of competing risk factors for liver disease.The present study is a follow-up investigation of the well-documented series of Irish women who were inadvertently infected with HCV as a result of receiving contaminated anti-D immunoglobulin (from a single source) in 1977 to 1978. [29][30][31] The contaminating HCV 1b was derived from a single infected donor. [30][31][32][33] The homogeneity of this group allows one to examine variation in host response to HCV infection without the potentially confounding influence of factors such as gender, specific HCV genotype, age range, and general health status. The purpose of the present study was to address whether particular HLA class II alleles are associated with clearance or persistence of HCV type 1b. PATIENTS AND METHODSThe study group consisted of 156 female individuals all of whom were iatrogenically infected between May 1977 and November 1978 with HCV type 1b from a single source. All 156 cases tested positive for antibodies to HCV (by recombinant immunoblot assay; Chiron Corporation, Emeryville, CA) and 46% (n ϭ 72) were positive for HCV RNA by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) using the Roche AMPLICOR test (F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland). The HCV status of the 84 patients who tested negative on initial qualitative HCV RT-PCR screening was confirmed by retesting within an 18-month period. The HCV genotype of the 72 virus-positive individuals was confirmed to be HCV 1b by reverse line probe assay (Inno-Lipa HCV II, INNOGENETICS N.V., Zwijndrecht, Belgium).Investigations were performed with informed consent and complied with a standardized protocol in compliance with standard of care and in accordance hospital eth...