Diagnostic Testing in Hepatitis C Virus Infection: Viral Kinetics and Genomics

Jean-Michel Pawlotsky

doi:10.1055/s-2003-41629

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2003; 23: 003-012
DOI: 10.1055/s-2003-41629

Diagnostic Testing in Hepatitis C Virus Infection: Viral Kinetics and Genomics

Jean-Michel Pawlotsky

Department of Virology, Henri Mondor Hospital, University of Paris XII, Créteil, France

Abstract

ABSTRACT

Virological tools play a major role in the diagnosis of hepatitis C virus (HCV) infection and in ongoing decision-making based on the patient's virological response to therapy. Virological tools used to assess viral kinetics and viral genomics can also be applied to clinical and translational research, especially in studies aimed at understanding the mechanisms underlying HCV treatment failure. Viral kinetics studies are based on quantification of HCV RNA at prescribed intervals during treatment and mathematical modeling of HCV RNA dynamics. These studies require sensitive and specific HCV RNA assays with an extended dynamic range of quantification. Viral genomics methods are useful to correlate viral kinetics with the intrinsic genomic characteristics of the HCV infecting strain. The interpretation of results utilizing various viral genomics tools is difficult, however, and must include predictive structural and functional genomic analyses. These approaches will be particularly useful in studying the mechanisms of HCV treatment failure with new HCV inhibitors currently under development.

KEYWORDS

Hepatitis C virus - HCV RNA quantification - viral kinetics - viral genomics - HCV resistance

Full Text

References

REFERENCES

1 Choo Q L, Kuo G, Weiner A J. et al . Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science . 1989; 244 359-362
2 Fried M W, Shiffman M L, Reddy K R. et al . Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med . 2002; 347 975-982
3 Hadziyannis S J, Cheinquer H, Morgan T. et al . Peginterferon alfa-2a (40 KD) (Pegasys) in combination with ribavirin (RBV): efficacy and safety results from a phase III, randomized, double-blind, multicentre study examining effect of duration of treatment and RBV dose. J Hepatol . 2002; 36(Suppl 1) 3
4 Manns M P, McHutchison J G, Gordon S C. et al . Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet . 2001; 358 958-965
5 Simmonds P. Viral heterogeneity of the hepatitis C virus. J Hepatol . 1999; 31(Suppl 1) 54-60
6 Soler M, Pellerin M, Malnou C E. et al . Quasispecies heterogeneity and constraints on the evolution of the 5' noncoding region of hepatitis C virus (HCV): relationship with HCV resistance to interferon-alpha therapy. Virology . 2002; 298 160-173
7 Ross R S, Viazov S O, Holtzer C D. et al . Genotyping of hepatitis C virus isolates using CLIP sequencing. J Clin Microbiol . 2000; 38 3581-3584
8 Ansaldi F, Torre F, Bruzzone B M. et al . Evaluation of a new hepatitis C virus sequencing assay as a routine method for genotyping. J Med Virol . 2001; 63 17-21
9 Stuyver L, Rossau R, Wyseur A. et al . Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. J Gen Virol . 1993; 74 1093-1102
10 Stuyver L, Wyseur A, van Arnhem W. et al . Hepatitis C virus genotyping by means of 5′-UR/core line probe assays and molecular analysis of untypeable samples. Virus Res . 1995; 38 137-157
11 Stuyver L, Wyseur A, van Arnhem W. et al . Second-generation line probe assay for hepatitis C virus genotyping. J Clin Microbiol . 1996; 34 2259-2266
12 Pawlotsky J M, Prescott L, Simmonds P. et al . Serological determination of hepatitis C virus genotype: comparison with a standardized genotyping assay. J Clin Microbiol . 1997; 35 1734-1739
13 Leruez-Ville M, Nguyen Q T, Cohen P. et al . Large-scale analysis of hepatitis C virus serological typing assay: effectiveness and limits. J Med Virol . 1998; 55 18-23
14 Prescott L E, Berger A, Pawlotsky J M. et al . Sequence analysis of hepatitis C virus variants producing discrepant results with two different genotyping assays. J Med Virol . 1997; 53 237-244
15 Sandres K, Dubois M, Pasquier C. et al . Determination of HCV genotype using two antibody assays and genome typing. Eur J Clin Microbiol Infect Dis . 2001; 20 666-669
16 Neumann A U, Lam N P, Dahari H. et al . Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science . 1998; 282 103-107
17 Bouvier-Alias M, Patel K, Dahari H. et al . Clinical utility of total hepatitis C virus (HCV) core antigen quantification, a new indirect marker of HCV replication. Hepatology . 2002; 36 211-218
18 Pawlotsky J M. Use and interpretation of virological tests for hepatitis C. Hepatology . 2002; 36 S65-S73
19 Consensus conference. Treatment of hepatitis C. Gastroenterol Clin Biol . 2002; 26 B303-B320
20 National Institutes of Health Consensus Development Conference Statement. Management of hepatitis C 2002 (June 10-12, 2002). Gastroenterology . 2002; 123 2082-2099
21 Hofer H, Watkins-Riedel T, Janata O. et al . Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load. Hepatology . 2003; 37 60-64
22 Zeuzem S, Herrmann E, Lee J H. et al . Viral kinetics in patients with chronic hepatitis C treated with standard or peginterferon alpha2a. Gastroenterology . 2001; 120 1438-1447
23 Lam N P, Neumann A U, Gretch D R. et al . Dose-dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa. Hepatology . 1997; 26 226-231
24 Neumann A U, Lam N P, Dahari H. et al . Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus. J Infect Dis . 2000; 182 28-35
25 Neumann A U, Buti M, Lurie Y. et al . The second phase HCV decline slope is the best predictor of sustained viral response during treatment of chronic HCV genotype 1 patients with peginterferon alfa-2b and ribavirin. Hepatology . 2002; 36 357A
26 Neumann A U, Zeuzem S, Ferrari C. et al . Ditto-HCV early viral kinetics report: novel decline patterns in genotype 1 but not genotypes 2 and 3 patients treated with peg-interferon alfa-2a and ribavirin. J Hepatol . 2002; 36(Suppl 1) 121
27 Pawlotsky J M, Neumann A U, Dahari H. et al . Hepatitis C virus dynamics during induction therapy with interferon alpha and/or ribavirin. Hepatology . 2000; 32 223A
28 Pawlotsky J M. Molecular diagnosis of viral hepatitis. Gastroenterology . 2002; 122 1554-1568
29 Urdea M S, Horn T, Fultz T J. et al . Branched DNA amplification multimers for the sensitive, direct detection of human hepatitis viruses. Nucleic Acids Symp Ser . 1991; 24 197-200
30 Saiki R K, Bugawan T L, Horn G T. et al . Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature . 1986; 324 163-166
31 Compton J. Nucleic acid sequence-based amplification. Nature . 1991; 350 91-92
32 Higuchi R, Fockler C, Dollinger G. et al . Kinetic PCR analysis: real-time monitoring of DNA amplification reactions. Biotechnology (NY) . 1993; 11 1026-1030
33 Heid C A, Stevens J, Livak K J. et al . Real time quantitative PCR. Genome Res . 1996; 6 986-994
34 Chen R W, Piiparinen H, Seppanen M. et al . Real-time PCR for detection and quantitation of hepatitis B virus DNA. J Med Virol . 2001; 65 250-256
35 Andrus A, Cox S, Beavers S. et al . High-throughput synthesis of functionalized oligonucleotides. Nucleic Acids Symp Ser . 1997; 317-318
36 Parks S B, Popovich B W, Press R D. Real-time polymerase chain reaction with fluorescent hybridization probes for the detection of prevalent mutations causing common thrombophilic and iron overload phenotypes. Am J Clin Pathol . 2001; 115 439-447
37 White P A, Pan Y, Freeman A J. et al . Quantification of hepatitis C virus in human liver and serum samples by using LightCycler reverse transcriptase PCR. J Clin Microbiol . 2002; 40 4346-4348
38 Komurian-Pradel F, Paranhos-Baccala G, Sodoyer M. et al . Quantitation of HCV RNA using real-time PCR and fluorimetry. J Virol Methods . 2001; 95 111-119
39 Yang J H, Lai J P, Douglas S D. et al . Real-time RT-PCR for quantitation of hepatitis C virus RNA. J Virol Methods . 2002; 102 119-128
40 Takeuchi T, Katsume A, Tanaka T. et al . Real-time detection system for quantification of hepatitis C virus genome. Gastroenterology . 1999; 116 636-642
41 Martell M, Gomez J, Esteban J I. et al . High-throughput real-time reverse transcription-PCR quantitation of hepatitis C virus RNA. J Clin Microbiol . 1999; 37 327-332
42 Enomoto M, Nishiguchi S, Shiomi S. et al . Comparison of real-time quantitative polymerase chain reaction with three other assays for quantitation of hepatitis C virus. J Gastroenterol Hepatol . 2001; 16 904-909
43 Lee C L, Schlag P, Antony A. et al . Evaluation of TaqMan HCV ASR. Hepatology . 2002; 36 346A
44 Saldanha J, Lelie N, Heath A. Establishment of the first international standard for nucleic acid amplification technology (NAT) assays for HCV RNA. Vox Sang . 1999; 76 149-158
45 Saldanha J, Heath A, Lelie N. et al . Calibration of HCV working reagents for NAT assays against the HCV international standard. Vox Sang . 2000; 78 217-224
46 Pawlotsky J M, Bouvier-Alias M, Hezode C. et al . Standardization of hepatitis C virus RNA quantification. Hepatology . 2000; 32 654-659
47 Chazouilleres O, Kim M, Combs C. et al . Quantitation of hepatitis C virus RNA in liver transplant recipients. Gastroenterology . 1994; 106 994-999
48 Duvoux C, Pawlotsky J M, Bastie A. et al . Low HCV replication levels in end-stage hepatitis C virus-related liver disease. J Hepatol . 1999; 31 593-597
49 Sulkowski M S, Thomas D L. Hepatitis C in the HIV-infected person. Ann Intern Med . 2003; 138 197-207
50 Thomas D L. Hepatitis C and human immunodeficiency virus infection. Hepatology . 2002; 36 S201-S209
51 Pawlotsky J M, Martinot-Peignoux M, Poveda J D. et al . Quantification of hepatitis C virus RNA in serum by branched DNA-based signal amplification assays. J Virol Methods . 1999; 79 227-235
52 Yu M L, Chuang W L, Dai C Y. et al . Clinical evaluation of the automated Cobas Amplicor HCV Monitor test version 2.0 for quantifying serum hepatitis C virus RNA and comparison to the Quantiplex HCV version 2.0 test. J Clin Microbiol . 2000; 38 2933-2939
53 Gerken G, Rothaar T, Rumi M G. et al . Performance of the Cobas Amplicor HCV Monitor test, version 2.0, an automated reverse transcription-PCR quantitative system for hepatitis C virus load determination. J Clin Microbiol . 2000; 38 2210-2214
54 Martinot-Peignoux M, Boyer N, Le Breton V. et al . A new step toward standardization of serum hepatitis C virus RNA quantification in patients with chronic hepatitis C. Hepatology . 2000; 31 726-729
55 Lee S C, Antony A, Lee N. et al . Improved version 2.0 qualitative and quantitative Amplicor reverse transcription-PCR tests for hepatitis C virus RNA: calibration to international units, enhanced genotype reactivity, and performance characteristics. J Clin Microbiol . 2000; 38 4171-4179
56 Pawlotsky J M. Measuring hepatitis C viremia in clinical samples: can we trust the assays?. Hepatology . 1997; 26 1-4
57 Pradat P, Chossegros P, Bailly F. et al . Comparison between three quantitative assays in patients with chronic hepatitis C and their relevance in the prediction of response to therapy. J Viral Hepat . 2000; 7 203-210
58 Reichard O, Norkrans G, Fryden A. et al . Comparison of 3 quantitative HCV RNA assays. Accuracy of baseline viral load to predict treatment outcome in chronic hepatitis C. Scand J Infect Dis . 1998; 30 441-446
59 Weiner A J, Brauer M J, Rosenblatt J. et al . Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology . 1991; 180 842-848
60 Martell M, Esteban J I, Quer J. et al . Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J Virol . 1992; 66 3225-3229
61 Pawlotsky J M, Germanidis G, Neumann A U. et al . Interferon resistance of hepatitis C virus genotype 1b: relationship to nonstructural 5A gene quasispecies mutations. J Virol . 1998; 72 2795-2805
62 Pawlotsky J M, Germanidis G, Frainais P O. et al . Evolution of the hepatitis C virus second envelope protein hypervariable region in chronically infected patients receiving alpha interferon therapy. J Virol . 1999; 73 6490-6499
63 Gretch D R, Polyak S J, Wilson J J. et al . Tracking hepatitis C virus quasispecies major and minor variants in symptomatic and asymptomatic liver transplant recipients. J Virol . 1996; 70 7622-7631
64 Polyak S J, McArdle S, Liu S L. et al . Evolution of hepatitis C virus quasispecies in hypervariable region 1 and the putative interferon sensitivity-determining region during interferon therapy and natural infection. J Virol . 1998; 72 4288-4296
65 Smith D B, McAllister J, Casino C. et al . Virus "quasispecies": making a mountain out of a molehill?. J Gen Virol . 1997; 78 1511-1519
66 Pawlotsky J M, Gretch D R. Molecular tools for the treatment of hepatitis C. Antivir Ther . 1998; 3 45-55
67 Pawlotsky J M. Antiviral treatment failure in chronic hepatitis C (in press). Antiviral Res. 2003;
68 Penin F, Dubuisson J, Rey F. et al . Structural biology of hepatitis C virus (in press). Hepatology . 2003;
69 McHutchison J G, Patel K. Future therapy of hepatitis C. Hepatology . 2002; 36 S245-S252
70 Benhamou Y, Hinrichsen H, Sentjens R. et al . Safety, tolerability and antiviral effect of BILN 2061, a novel HCV serine protease inhibitor, after oral treatment over two days in patients with chronic hepatitis C, genotype 1, with advanced liver fibrosis. Hepatology . 2002; 36 304A
71 Hinrichsen H, Benhamou Y, Reiser M. et al . First report on the antiviral efficacy of BILN 2061, a novel oral serine protease inhibitor, in patients with chronic hepatitis C genotype 1. Hepatology . 2002; 36 379A
72 De Francesco R, Rice C M. New therapies on the horizon for hepatitis C: are we close ?. Clin Liver Dis . 2003; 7 211-242
73 Soler M, Penin F, Ray S. et al . Hepatitis C virus NS3 serine protease variability and evolution are strongly constrained by the need for structural and functional conservation. J Hepatol . 2002; 36(Suppl 1) 5
74 Pietschmann T, Bartenschlager R. Tissue culture and animal models for hepatitis C virus. Clin Liver Dis . 2003; 7 23-43