Case report: Clinical and virological analyses of a patient positive for hepatitis C virus-RNA by branched DNA assay but negative for anti-hepatitis C virus antibodies.
Infection with hepatitis C virus (HCV) is usually diagnosed by the presence of antibodies against fusion proteins or peptides derived from different regions of the HCV genome. However, a subgroup of patients with HCV viraemia are seronegative for antibody against hepatitis C virus (anti-HCV) by conventional antibody assays. We analysed serum samples from a patient with liver cirrhosis who tested negative for anti-HCV by a second-generation assay, but positive for HCV-RNA by reverse transcription polymerase chain reaction (RT-PCR) and branched DNA signal amplification. To identify possible mutations that could explain the failure of detection of anti-HCV by second-generation assay, PCR-amplified DNA fragments of the core region derived from the serum were cloned and sequenced. Nucleotide (nt) and amino acid (aa) sequence analyses (nt 1-486, aa 1-162) showed no mutations revealing stop codons, frame-shifts, deletions or insertions, but the presence of two amino acid substitutions (aa 75 and 91) when compared with HCV-J, a prototype strain of genotype 1b isolated from a Japanese patient. One of these two mutations (aa 75) was situated in the second hydrophilic domain of the core peptide, but analysis of the hydropathy profile showed only a little change. The two mutations were identical to those identified in other Japanese HCV isolates. The serum immunoglobulin level and T and B cell counts were normal in our patient. Our data suggest that the absence of anti-HCV in this patient was not due to mutations of major epitopes of HCV. Low-dose prednisolone administration just after transfusion may have induced immunological tolerance against HCV in this patient.
Suzuki
F
F
The Second Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.
Chayama
K
K
Nakajima
T
T
Kawasaki
T
T
Kumada
H
H
Yoshimi
T
T
D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis*; D016174:Hepacivirus / Q000235:genetics*; D018937:Hepatitis C Antibodies / Q000032:analysis*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis*; D014158:Transcription, Genetic
D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D004247:DNA