The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies

Science

Volumn 288, Issue 5464, 2000, Pages 339-344

  Farci, Patrizia ^a,b   Shimoda, Atsushi ^c   Coiana, Alessandra ^a   Diaz, Giacomo ^a   Peddis, Giovanna ^a   Melpolder, Jacqueline C ^d   Strazzera, Antonello ^a   Chien, David Y ^e   Munoz, Santiago J ^f   Balestrieri, Angelo ^a   Purcell, Robert H ^b   Alter, Harvey J ^d  

^a UNIVERSITY OF CAGLIARI   (Italy)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^c KANAZAWA UNIVERSITY   (Japan)

^d NATIONAL INSTITUTES OF HEALTH   (United States)

^e NOVARTIS PHARMA AG   (Switzerland)

^f ALBERT EINSTEIN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEPATITIS C ANTIBODY; VIRUS ENVELOPE PROTEIN;

ACUTE HEPATITIS; ADULT; ARTICLE; CHRONICITY; CLINICAL ARTICLE; ENVELOPE GENE; EVOLUTION; GENE SEQUENCE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; IMMUNE SYSTEM; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; REMISSION; SEROCONVERSION; VIRUS CELL INTERACTION;

ACUTE DISEASE; ADULT; AGED; ANTIBODIES, VIRAL; DISEASE PROGRESSION; EVOLUTION, MOLECULAR; FEMALE; GENES, VIRAL; HEPACIVIRUS; HEPATITIS C; HEPATITIS C ANTIBODIES; HEPATITIS C, CHRONIC; HUMANS; MALE; MIDDLE AGED; MOLECULAR SEQUENCE DATA; PHYLOGENY; PROSPECTIVE STUDIES; SELECTION (GENETICS); TIME FACTORS; VARIATION (GENETICS); VIRAL ENVELOPE PROTEINS; VIRUS REPLICATION;

HEPATITIS C VIRUS; RNA VIRUSES;

EID: 0034646996     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.288.5464.339     Document Type: Article

References (58)

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21. A total of 12 patients were included in this study. Ten patients, four women and six men (mean age ± SD, 58.5 ± 12.74 years), were derived from a prospective study of post-transfusion non-A, non-B hepatitis conducted at NIH [D. E. Koziol et al., Ann. Intern. Med. 104, 488 (1986)]. One patient had FH, three had acute self-limited hepatitis, and six had acute hepatitis that progressed to chronicity. The remaining two patients with FH were derived from a study on the prevalence of HCV in non-A, non-B FH conducted at Jefferson Hospital, Philadelphia (S. J. Munoz, unpublished data). Both patients were females, mean age 51.0 ± 22.6 years. For patient 2 the risk factor for HCV infection was transfusion of red blood cells; there were no known risk factors for patient 3 (Table 1). Patient 2 was referred for liver transplantation for cryptogenic end-stage liver cirrhosis. Because of her chronic anemia, she was transfused before the first liver transplantation, prior to the introduction of universal anti-HCV screening. The patient seroconverted about 10 days after the first liver transplantation and 6 weeks later developed fulminant hepatic failure for which she received the second liver transplantation, but several weeks later died in hepatic coma [P. Farci et al., J. Infect. Dis. 179, 1007 (1999)]. Serial serum samples were available from all 12 patients, except patient 3, for whom only a single sample was available. This patient died of fulminant hepatic failure a few days after admission to the hospital.
22. A total of 12 patients were included in this study. Ten patients, four women and six men (mean age ± SD, 58.5 ± 12.74 years), were derived from a prospective study of post-transfusion non-A, non-B hepatitis conducted at NIH [D. E. Koziol et al., Ann. Intern. Med. 104, 488 (1986)]. One patient had FH, three had acute self-limited hepatitis, and six had acute hepatitis that progressed to chronicity. The remaining two patients with FH were derived from a study on the prevalence of HCV in non-A, non-B FH conducted at Jefferson Hospital, Philadelphia (S. J. Munoz, unpublished data). Both patients were females, mean age 51.0 ± 22.6 years. For patient 2 the risk factor for HCV infection was transfusion of red blood cells; there were no known risk factors for patient 3 (Table 1). Patient 2 was referred for liver transplantation for cryptogenic end-stage liver cirrhosis. Because of her chronic anemia, she was transfused before the first liver transplantation, prior to the introduction of universal anti-HCV screening. The patient seroconverted about 10 days after the first liver transplantation and 6 weeks later developed fulminant hepatic failure for which she received the second liver transplantation, but several weeks later died in hepatic coma [P. Farci et al., J. Infect. Dis. 179, 1007 (1999)]. Serial serum samples were available from all 12 patients, except patient 3, for whom only a single sample was available. This patient died of fulminant hepatic failure a few days after admission to the hospital.
23. A total of 12 patients were included in this study. Ten patients, four women and six men (mean age ± SD, 58.5 ± 12.74 years), were derived from a prospective study of post-transfusion non-A, non-B hepatitis conducted at NIH [D. E. Koziol et al., Ann. Intern. Med. 104, 488 (1986)]. One patient had FH, three had acute self-limited hepatitis, and six had acute hepatitis that progressed to chronicity. The remaining two patients with FH were derived from a study on the prevalence of HCV in non-A, non-B FH conducted at Jefferson Hospital, Philadelphia (S. J. Munoz, unpublished data). Both patients were females, mean age 51.0 ± 22.6 years. For patient 2 the risk factor for HCV infection was transfusion of red blood cells; there were no known risk factors for patient 3 (Table 1). Patient 2 was referred for liver transplantation for cryptogenic end-stage liver cirrhosis. Because of her chronic anemia, she was transfused before the first liver transplantation, prior to the introduction of universal anti-HCV screening. The patient seroconverted about 10 days after the first liver transplantation and 6 weeks later developed fulminant hepatic failure for which she received the second liver transplantation, but several weeks later died in hepatic coma [P. Farci et al., J. Infect. Dis. 179, 1007 (1999)]. Serial serum samples were available from all 12 patients, except patient 3, for whom only a single sample was available. This patient died of fulminant hepatic failure a few days after admission to the hospital.
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30. The viral population diversity was calculated by analysis of predicted amino acid sequences, 186 amino acids in length, amplified from the E1 and E2 genes of the HCV genome, including the 31 amino acids of HVR1. The genetic diversity was calculated by the Hamming distance, which is defined as the number of amino acid differences between two sequences [R. W. Hamming, Coding and Information Theory (Prentice-Hall, Englewood Cliffs, NJ, ed. 2, 1986)]. The mean Hamming distance (that is, the average of the values taken for all sequence pairs derived from a single sample) was separately calculated on HVR1 (31 amino acids) and on the entire sequence outside HVR1 (155 amino acids). More details of this analysis are given in Science Online (www. sciencemag.org/feature/data/1047689.shl).
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35. The average number of synonymous substitutions per synonymous site and the number of nonsynonymous substitutions per nonsynonymous site relative to the ancestral consensus sequence were calculated [M. Nei and T. Gojobori, Mol. Biol. Evol. 3, 418 (1986)] for each time point within a single patient with the use of the program MEGA [S. Kumar, K. Tamura, M. Nei, Molecular Evolutionary Genetics Analysis (MEGA) version 1.01, Institute of Molecular Evolutionary Genetics, Pennsylvania State University]. The consensus sequence from the first time point was used as a reference. Comparison of the mean number (±SEM) of synonymous and nonsynonymous nucleotide substitutions per site per week between progressing and resolving or FH was performed by unpaired Welch's t test (31). In FH, the analysis was restricted to two patients, because only a single sample was available from patient 3 (12).
36. The average number of synonymous substitutions per synonymous site and the number of nonsynonymous substitutions per nonsynonymous site relative to the ancestral consensus sequence were calculated [M. Nei and T. Gojobori, Mol. Biol. Evol. 3, 418 (1986)] for each time point within a single patient with the use of the program MEGA [S. Kumar, K. Tamura, M. Nei, Molecular Evolutionary Genetics Analysis (MEGA) version 1.01, Institute of Molecular Evolutionary Genetics, Pennsylvania State University]. The consensus sequence from the first time point was used as a reference. Comparison of the mean number (±SEM) of synonymous and nonsynonymous nucleotide substitutions per site per week between progressing and resolving or FH was performed by unpaired Welch's t test (31). In FH, the analysis was restricted to two patients, because only a single sample was available from patient 3 (12).
37. For each patient, we calculated the median branch lengths and the range from the ancestral node to all taxa from a single time point, based on Kimura's distance to generate a neighbor-joining tree. The time point after antibody seroconversion was used for this analysis. The median branch lengths and the range were as follows (patient numbers refer to Table 1): patient 1, week 7, 0.000 (0.000-0.000); patient 2, week 8, 0.000 (0.000-0.033); patient 3, 0.000 (0.000-0.034) [the time of infection was unknown (Table 1) (12)]; patient 4, week 12, 0.017 (0.000-0.142); patient 5, week 10, 0.000 (0.000-0.106); patient 6, week 5, 0.000 (0.000-0.068); patient 7, week 11, 0.085 (0.033-0.318); patient 8, week 18, 0.422 (0.422-0.581); patient 9, week 9, 0.000 (0.000-0.308); patient 10, week 13, 0.265 (0.000-0.469); patient 11, week 16, 0.094 (0.000-0.094); patient 12, week 18, 0.033 (0.000-0.070). There was a trend toward an increase in the branch length from fulminant (patients 1 to 3) to acute resolving (patients 4 to 6) to progressing hepatitis (patients 7 to 12). One exception was represented by the median of patient 9, although the same case had a branch length maximum consistent with the trend observed in progressing hepatitis.
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58. We thank E. Pascariello and A. Brambilla for their help in genetic analysis, P. Lusso for critical reading of the manuscript, and C. Bosoni and H. Newman for editorial assistance. Sequences have been submitted to GenBank under accession numbers AF245706 and AF246119.