Abstract
Although acute hepatitis C virus (HCV) infection is a rare disease and typically not
associated with severe clinical symptoms, it has become a disease of significant interest
for clinical investigators, virologists, and immunologists alike. In the same way
that acute hepatitis C provided a window of opportunity for understanding the clinical
and virological aspects of HCV infection as the field was being established, it is
now clear that it can provide a window into further understanding the early interaction
of the virus with the host immune response. The acute phase of infection is usually
considered to be the first 6 months; however, rather than defining acute HCV by the
time that has passed after initial infection, it can also be defined as the biological
state in which spontaneous clearance is still possible.
KEYWORDS
Acute - liver - hepatitis C virus - treatment - interferon - T cell - immune response
REFERENCES
- 1
Alter M J, Hadler S C, Judson F N et al..
Risk factors for acute non-A, non-B hepatitis in the United States and association
with hepatitis C virus antibody.
JAMA.
1990;
264
2231-2235
- 2
Alter H J, Purcell R H, Shih J W et al..
Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients
with acute and chronic non-A, non-B hepatitis.
N Engl J Med.
1989;
321
1494-1500
- 3
Schlauder G G, Leverenz G J, Amann C W et al..
Detection of the hepatitis C virus genome in acute and chronic experimental infection
in chimpanzees.
J Clin Microbiol.
1991;
29
2175-2179
- 4
Alberti A, Boccato S, Vario A, Benvegnu L.
Therapy of acute hepatitis C.
Hepatology.
2002;
36
S195-S200
- 5
Alberti A, Chemello L, Benvegnu L.
Natural history of hepatitis C.
J Hepatol.
1999;
31(Suppl 1)
17-24
- 6
Villano S A, Vlahov D, Nelson K E et al..
Persistence of viremia and the importance of long-term follow-up after acute hepatitis
C infection.
Hepatology.
1999;
29
908-914
- 7
Thomas D L, Astemborski J, Rai R M et al..
The natural history of hepatitis C virus infection: host, viral, and environmental
factors.
JAMA.
2000;
284
450-456
- 8
Gerlach J T, Diepolder H M, Zachoval R et al..
Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance.
Gastroenterology.
2003;
125
80-88
- 9
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
- 10
Larghi A, Zuin M, Crosignani A et al..
Outcome of an outbreak of acute hepatitis C among healthy volunteers participating
in pharmacokinetics studies.
Hepatology.
2002;
36
993-1000
- 11
Bigger C B, Brasky K M, Lanford R E.
DNA microarray analysis of chimpanzee liver during acute resolving hepatitis C virus
infection.
J Virol.
2001;
75
7059-7066
- 12
Rahman F, Heller T, Sobao Y et al..
Effects of antiviral therapy on the cellular immune response in acute hepatitis C.
Hepatology.
2004;
40
87-97
- 13
Lefrere J J, Roudot-Thoraval F, Lunel F et al..
Expertise of French laboratories in detection, genotyping, and quantification of hepatitis
C virus RNA in serum.
J Clin Microbiol.
2004;
42
2027-2030
- 14
Pawlotsky J M.
Diagnostic testing in hepatitis C virus infection: viral kinetics and genomics.
Semin Liver Dis.
2003;
23(suppl 1)
3-11
- 15
Krogsgaard K, Wantzin P, Mathiesen L R et al..
Early appearance of antibodies to hepatitis C virus in community acquired acute non-A,
non-B hepatitis is associated with progression to chronic liver disease. The Copenhagen
Hepatitis Acuta Programme.
Scand J Infect Dis.
1990;
22
399-402
- 16
Kryczka W, Walewska-Zielecka B, Dutkiewicz E.
Acute seronegative hepatitis C manifesting itself as adult giant cell hepatitis-a
case report and review of literature.
Med Sci Monit.
2003;
9(Suppl 3)
29-31
- 17
Morand P, Dutertre N, Minazzi H et al..
Lack of seroconversion in a health care worker after polymerase chain reaction-documented
acute hepatitis C resulting from a needlestick injury.
Clin Infect Dis.
2001;
33
727-729
- 18
Seeff L B, Hollinger F B, Alter H J et al..
Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type
C hepatitis: A National Heart, Lung, and Blood Institute collaborative study.
Hepatology.
2001;
33
455-463
- 19
Takaki A, Wiese M, Maertens G et al..
Cellular immune responses persist, humoral responses decrease two decades after recovery
from a single source outbreak of hepatitis C.
Nat Med.
2000;
6
578-582
- 20
Cerny A, McHutchison J G, Pasquinelli C et al..
Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the
HLA A2.1 binding motif.
J Clin Invest.
1995;
95
521-530
- 21
Rehermann B, Chang K M, McHutchison J G et al..
Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response, disease
activity and viral load in patients with chronic hepatitis C virus infection.
J Clin Invest.
1996;
98
1432-1440
- 22
Rehermann B, Chang K M, McHutchison J et al..
Differential cytotoxic T lymphocyte responsiveness to the hepatitis B and C viruses
in chronically infected patients.
J Virol.
1996;
70
7092-7102
- 23
Chang K M, Gruener N H, Southwood S et al..
Identification of HLA-A3 and -B7-restricted CTL response to hepatitis C virus in patients
with acute and chronic hepatitis C.
J Immunol.
1999;
162
1156-1164
- 24
Lauer G M, Ouchi K, Chung R T et al..
Comprehensive analysis of CD8( + )-T-cell responses against hepatitis C virus reveals
multiple unpredicted specificities.
J Virol.
2002;
76
6104-6113
- 25
Lauer G M, Barnes E, Lucas M et al..
High resolution analysis of cellular immune responses in resolved and persistent hepatitis
C virus infection.
Gastroenterology.
2004;
127
924-936
- 26
Lechner F, Wong D K, Dunbar P R et al..
Analysis of successful immune responses in persons infected with hepatitis C virus.
J Exp Med.
2000;
191
1499-1512
- 27
Wedemeyer H, He X -S, Nascimbeni M et al..
Impaired effector function of hepatitis C virus-specific CD8 + T cells in chronic
hepatitis C virus infection.
J Immunol.
2002;
169
3447-3458
- 28
Su A I, Pezacki J P, Wodicka L et al..
Genomic analysis of the host response to hepatitis C virus infection.
Proc Natl Acad Sci USA.
2002;
99
15669-15674
- 29
Khakoo S I, Thio C L, Martin M P et al..
HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection.
Science.
2004;
305
872-874
- 30
Diepolder H M, Zachoval R, Hoffmann R M et al..
Possible mechanism involving T lymphocyte response to non-structural protein 3 in
viral clearance in acute hepatitis C virus infection.
Lancet.
1995;
346
1006-1007
- 31
Diepolder H M, Gerlach J -T, Zachoval R et al..
Immunodominant CD4 + T-cell epitope within nonstructural protein 3 in acute hepatitis
C virus infection.
J Virol.
1997;
71
6011-6019
- 32
Missale G, Bertoni R, Lamonaca V et al..
Different clinical behaviors of acute hepatitis C virus infection are associated with
different vigor of the anti-viral cell-mediated immune response.
J Clin Invest.
1996;
98
706-714
- 33
Lamonaca V, Missale G, Urbani S et al..
Conserved hepatitis C virus sequences are highly immunogenic for CD4( + ) T cells:
implications for vaccine development.
Hepatology.
1999;
30
1088-1098
- 34
Gerlach J T, Diepolder H M, Jung M C et al..
Recurrence of hepatitis C virus after loss of virus-specific CD4( + ) T-cell response
in acute hepatitis C.
Gastroenterology.
1999;
117
933-941
- 35
Thimme R, Oldach D, Chang K M et al..
Determinants of viral clearance and persistence during acute hepatitis C virus infection.
J Exp Med.
2001;
194
1395-1406
- 36
Cooper S, Erickson A L, Adams E J et al..
Analysis of a successful immune response against hepatitis C virus.
Immunity.
1999;
10
439-449
- 37
Shoukry N, Grakoui A, Houghton M et al..
Memory CD8 + T cells are required for protection from persistent hepatitis C virus
infection.
J Exp Med.
2003;
197
1645-1655
- 38
Gerlach T J, Diepolder H M, Gruener N H et al..
Symptomatic acute hepatitis C: when to treat?.
Hepatology.
1999;
30
195A
- 39
Farci P, Alter H J, Wong D C et al..
Prevention of hepatitis C virus infection in chimpanzees after antibody- mediated
in vitro neutralization.
Proc Natl Acad Sci USA.
1994;
91
7792-7796
- 40
Adams G, Kuntz S, Rabalais G et al..
Natural recovery from acute hepatitis C virus infection by agammaglobulinemic twin
children.
Pediatr Infect Dis J.
1997;
16
533-534
- 41
Christie J M, Healey C J, Watson J et al..
Clinical outcome of hypogammaglobulinaemic patients following outbreak of acute hepatitis
C: 2 year follow up.
Clin Exp Immunol.
1997;
110
4-8
- 42
Baumert T F, Wellnitz S, Aono S et al..
Antibodies against hepatitis C virus-like particles and viral clearance in acute and
chronic hepatitis C.
Hepatology.
2000;
32
610-617
- 43
Bartosch B, Dubuisson J, Cosset F L.
Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope
protein complexes.
J Exp Med.
2003;
197
633-642
- 44
Hsu M, Zhang J, Flint M et al..
Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral
particles.
Proc Natl Acad Sci USA.
2003;
100
7271-7276
- 45
Logvinoff C, Major M E, Oldach D et al..
Neutralizing antibody response during acute and chronic hepatitis C virus infection.
Proc Natl Acad Sci USA.
2004;
101
10149-10154
- 46
Farci P, Shimoda A, Coiana A et al..
The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies.
Science.
2000;
288
339-344
- 47
Fitzgerald K A, McWhirter S M, Faia K L et al..
IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.
Nat Immunol.
2003;
4
491-496
- 48
Yoneyama M, Kikuchi M, Natsukawa T et al..
The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate
antiviral responses.
Nat Immunol.
2004;
5
730-737
- 49
Balachandran S, Thomas E, Barber G N.
A FADD-dependent innate immune mechanism in mammalian cells.
Nature.
2004;
432
401-405
- 50
Foy E, Li K, Wang C et al..
Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease.
Science.
2003;
300
1145-1148
- 51
Taylor D R, Shi S T, Romano P R et al..
Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein.
Science.
1999;
285
107-110
- 52
Gale M J, Korth M J, Katze M G.
Repression of the PKR protein kinase by the hepatitis C virus NS5A protein: a potential
mechanism of interferon resistance.
Clin Diagn Virol.
1998;
10
157-162
- 53
Crotta S, Stilla A, Wack A et al..
Inhibition of natural killer cells through engagement of CD81 by the major hepatitis
C Virus envelope protein.
J Exp Med.
2002;
195
35-42
- 54
Tseng C T, Klimpel G R.
Binding of the hepatitis C virus envelope protein E2 to CD81 inhibits natural killer
cell functions.
J Exp Med.
2002;
195
43-49
- 55
Spada E, Mele A, Berton A et al..
Multispecific T cell response and negative HCV RNA tests during acute HCV infection
are early prognostic factors of spontaneous clearance.
Gut.
2004;
53
1673-1681
- 56
Pham T N, MacParland S A, Mulrooney P M et al..
Hepatitis C virus persistence after spontaneous or treatment-induced resolution of
hepatitis C.
J Virol.
2004;
78
5867-5874
- 57
Nascimbeni M, Mizukoshi E, Bosmann M et al..
Kinetics of CD4 + and CD8 + memory T cell responses during hepatitis C virus rechallenge
of previously recovered chimpanzees.
J Virol.
2003;
77
4781-4793
- 58
Timm J, Lauer G, Kavanagh D G et al..
CTL escape and reversion in acute HCV infection.
J Exp Med.
2004;
200
1593-1604
- 59
Erickson A L, Kimura Y, Igarashi S et al..
The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes
targeted by cytotoxic T lymphocytes.
Immunity.
2001;
15
883-895
- 60
Seifert U, Liermann H, Racanelli V et al..
Hepatitis C virus mutation affects proteasomal epitope processing.
J Clin Invest.
2004;
114
250-259
- 61
Chang K M, Rehermann B, McHutchison J G et al..
Immunological significance of cytotoxic T lymphocyte epitope variants in patients
chronically infected by the hepatitis C virus.
J Clin Invest.
1997;
100
2376-2385
- 62
Tsai S L, Chen Y M, Chen M H et al..
Hepatitis C virus variants circumventing cytotoxic T lymphocyte activity as a mechanism
of chronicity.
Gastroenterology.
1998;
115
954-965
- 63
Valitutti S, Müller S, Cella M et al..
Serial triggering of many T-cell receptors by a few peptide-MHC complexes.
Nature.
1995;
375
148-151
- 64
Moore C B, John M, James I R et al..
Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level.
Science.
2002;
296
1439-1443
- 65
Allen T M, Altfeld M, Yu X G et al..
Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte
escape mutation in human immunodeficiency virus type 1 infection.
J Virol.
2004;
78
7069-7078
- 66
Frasca L, Del Porto P, Tuosto L et al..
Hypervariable region 1 variants act as TCR antagonists for hepatitis C virus-specific
CD4 + T cells.
J Immunol.
1999;
163
650-658
- 67
Shimizu Y K, Hijikita M, Iwamoto A et al..
Neutralizing antibodies against hepatitis C virus and the emergence of neutralization
escape mutant viruses.
J Virol.
1994;
68
1494-1500
- 68
Appay V, Dunbar P R, Callan M et al..
Memory CD8 + T cells vary in differentiation phenotype in different persistent virus
infections.
Nat Med.
2002;
8
379-385
- 69
Francavilla V, Accapezzato D, De Salvo M et al..
Subversion of effector CD8 + T cell differentiation in acute hepatitis C virus infection:
exploring the immunological mechanisms.
Eur J Immunol.
2004;
34
427-437
- 70
Koziel M J, Dudley D, Wong J T et al..
Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with
chronic hepatitis.
J Immunol.
1992;
149
3339-3344
- 71
Koziel J M, Dudley D, Afdhal N et al..
Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the
core and envelope proteins of HCV.
J Virol.
1993;
67
7522-7532
- 72
Koziel M J, Dudley D, Afdhal N et al..
HLA class I-restricted cytotoxic T lymphocytes specific for hepatitis C virus. Identification
of multiple epitopes and characterization of patterns of cytokine release.
J Clin Invest.
1995;
96
2311-2321
- 73
Koziel M J, Walker B D.
Characteristics of the intrahepatic cytotoxic T lymphocyte response in chronic hepatitis
C virus infection.
Springer Semin Immunopathol.
1997;
19
69-83
- 74
Diepolder H M, Zachoval R, Hoffmann R M et al..
The role of hepatitis C virus specific CD4 + T lymphocytes in acute and chronic hepatitis
C.
J Mol Med.
1996;
74
583-588
- 75
Kittlesen D J, Chianese-Bullock K A, Yao Z Q et al..
Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits
T-lymphocyte proliferation.
J Clin Invest.
2000;
106
1239-1249
- 76
Eisen-Vandervelde A L, Waggoner S N, Yao Z Q et al..
Hepatitis C virus core selectively suppresses interleukin-12 synthesis in human macrophages
by interfering with AP-1 activation.
J Biol Chem.
2004;
279
43479-43486
- 77
Yao Z Q, Ray S, Eisen-Vandervelde A et al..
Hepatitis C virus: immunosuppression by complement regulatory pathway.
Viral Immunol.
2001;
14
277-295
- 78
Camma C, Almasio P, Craxi A.
Interferon as treatment for acute hepatitis C. A meta-analysis.
Dig Dis Sci.
1996;
41
1248-1255
- 79
Quin J.
Interferon therapy for acute hepatitis C viral infection-a review by meta-analysis.
Aust N Z J Med.
1997;
27
611-618
- 80
Thevenot T, Regimbeau C, Ratziu V et al..
Meta-analysis of interferon randomized trials in the treatment of viral hepatitis
C in naive patients: 1999 update.
J Viral Hepat.
2001;
8
48-62
- 81
Poynard T, Regimbeau C, Myers R P et al..
Interferon for acute hepatitis C.
Cochrane Database Syst Rev.
2002;
(1)
CD000369
- 82
Jaeckel E, Cornberg M, Wedemeyer H et al..
Treatment of acute hepatitis C with interferon alfa-2b.
N Engl J Med.
2001;
345
1452-1457
- 83
Vogel W, Graziadei I, Umlauft F et al..
High-dose interferon-alpha2b treatment prevents chronicity in acute hepatitis C: a
pilot study.
Dig Dis Sci.
1996;
41
81S-85S
- 84
Licata A, Di Bona D, Schepis F et al..
When and how to treat acute hepatitis C?.
J Hepatol.
2003;
39
1056-1062
- 85
Kamal S M, Ismail A, Graham C S et al..
Pegylated interferon alpha therapy in acute hepatitis C: relation to hepatitis C virus-specific
T cell response kinetics.
Hepatology.
2004;
39
1721-1731
- 86
Lauer G M, Lucas M, Ouchi K et al..
T cell responses during early therapy for HCV infection.
Hepatology.
2003;
38
354A
- 87
Tester I A, Smyk-Pearson S, Dean S, Rosen H R.
Acute hepatitis C infection following patellar tendon transplantation: immunologic
correlates of recovery.
Hepatology.
2003;
38
358A
- 88
Kaplan D, Sugimoto K, Ikeda F et al..
Differential mechanism of interferon-induced and spontaneous clearance of hepatitis
C virus infection.
Hepatology.
2003;
38
357A
- 89
Nomura H, Sou S, Tanimoto H et al..
Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled
trial.
Hepatology.
2004;
39
1213-1219
- 90
Major M E, Dahari H, Mihalik K et al..
Hepatitis C virus kinetics and host responses associated with disease and outcome
of infection in chimpanzees.
Hepatology.
2004;
39
1709-1720
Barbara RehermannM.D.
Liver Diseases Branch, NIDDK, National Institutes of Health
DHHS, Bldg. 10, Room 9B16, 10 Center Drive
Bethesda, MD 20892
Email: Rehermann@nih.gov