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Dtsch Med Wochenschr 2003; 128(38): 1963-1968
DOI: 10.1055/s-2003-42367
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© Georg Thieme Verlag Stuttgart · New York

Hepatitis C: Update

Hepatitis C: updateTh Hügle1 , A. Cerny1
  • 1Clinica Medica, Ospedale Civico, Lugano
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Publication History

eingereicht: 17.12.2002

akzeptiert: 7.7.2003

Publication Date:
19 September 2003 (online)

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Hepatitis C: UpdateDtsch Med Wochenschr 2003; 128(50): 2668-2668
DOI: 10.1055/s-2003-45487

Glossar

HCV = Hepatitis-C-Virus

HIV = Humanes Immundefizienz-Virus

HCC = Hepatozelluläres Karzinom

PEG = Polyethylenglycol

IFN = Interferon

SVR = sustained viral response, anhaltende Therapieantwort

EVR = early viral response, frühe Therapieantwort

PCR = Polymerase-Kettenreaktion

ELISA = Enzyme-linked-immunosorbent-assay

RIBA = Rekombinanter-immunoblot-assay

Weltweit ist das Hepatitis-C-Virus (HCV) eine der häufigsten Ursachen für die chronische Hepatitis, die Leberzirrhose und das hepatozelluläre Karzinom (HCC). Das HCV ist ein einzelsträngiges, positiv orientiertes RNA-Virus und gehört damit zur Familie der Flaviviridae. Die Übertragung verläuft parenteral durch Blut oder Blutprodukte. Seit der Einführung des systematischen HCV-Screenings ist der intravenöse Drogenkonsum einem der häufigsten Übertragungswege geworden. In bis zu 40 % bleibt die Ursache der Übertragung jedoch unklar. Neben der chronischen Hepatitis wird das HCV auch mit extrahepatischen Erkrankungen wie z. B. der Kryoglobulinämie, dem Sjögren-Syndrom oder Non-Hodgin-Lymphomen in Verbindung gebracht. Die Therapie dieser Infektion gestaltet sich vor allem für den häufigen Genotyp 1 immer noch als schwierig, jedoch kann mit Hilfe von Polyethylenglycol (PEG)-konjugiertem Interferon (INF)-α in Kombination mit dem Nukleosidanalogon Ribavirin in Genotyp 2 und 3 in bis zu 80 % eine „anhaltende virologische Antwort” (sustained virological response, SVR) erreicht werden. Der Fortschritt der molekularen Virologie der Hepatitis C hat außerdem neue gentechnologische Therapieansätze ermöglicht, die auf der Hemmung der Virus-Replikation, Genexpression oder der Stärkung der Immunantwort gegen das HCV basieren und sich bereits in klinischer Erprobung befinden. Von einer baldigen Entwicklung der effizienten Vakzinierung kann aufgrund der hohen genetischen Variabilität leider noch nicht ausgegangen werden.

Literatur

  • 1 Azzari C. et al . Vertical transmission of HCV is related to maternal peripheral blood mononuclear cell infection.  Blood. 2000;  15 2045
    Search in Google Scholar
  • 2 Beckebaum S, Cicinnati V R, Gerken G. DNA-based immunotherapy: potential for treatment of chronic viral hepatitis?.  Rev Med Virol. 2002;  12 297
    Search in Google Scholar
  • 3 Benhamou Y. et al . Safety, tolerability and antiviral effect of BILN 2061, a novel HCV serine protease inhibitor, after oral treatment over 2 days in patients with chronic hepatitis C, genotype 1 with advanced liver fibrosis.  Hepatology. 2002;  36 563A
    Search in Google Scholar
  • 4 Bgvv. Bundesinstitut für Risikobewertung .Hepatitis C und Stillen. http://www.bgvv.de/sixcms_upload/media/113/hepatitis_c_stillen.pdf 2001
    Search in Google Scholar
  • 5 Brillanti S, Levantesi F, Masi L, Foli M, Bolondi L. Triple antiviral therapy as a new option for patients with interferon nonresponsive chronic hepatitis C.  Hepatology. 2000;  32 630
    Search in Google Scholar
  • 6 Cacoub P. et al . Lower expression of CD81 B-cell receptor in lymphoproliferative diseases associated with hepatitis C virus infection.  J Viral Hepat. 2003;  10 10
    Search in Google Scholar
  • 7 Cerny A, Chisari F. Pathogenesis of chronic hepatitis C: immunological features of hepatic injury and viral persistence.  Hepatology. 1999;  30 595
    Search in Google Scholar
  • 8 Conry-Cantilena C. et al . Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection.  N Engl J Med. 1996;  334 1691
    Search in Google Scholar
  • 9 EASL. European Association for the Study of the Liver . Consensus Statement.  J Hepatol. 1999;  30 956
    Search in Google Scholar
  • 10 El-Serag H B, Mason A C. Risk factors for the rising rates of primary liver cancer in the United States.  Arch Intern Med. 2000;  160 3227
    Search in Google Scholar
  • 11 Eren R. et al . Development and clinical evaluation of human monoclonal antibodies for treating HCV infection.  Hepatology. 2002;  36 498A
    Search in Google Scholar
  • 12 Erhardt A. et al . Hepatocellular carcinoma: rising incidence of hepatitis C virus-associated cases at a university clinic in Germany.  Dtsch Med Wochenschr. 2002;  127 2665
    Search in Google Scholar
  • 13 Farci P. et al . Lack of protective immunity against reinfection with hepatitis C virus.  Science. 1992;  258 135
    Search in Google Scholar
  • 14 Forns X. et al . Vaccination of chimpanzees with plasmid DNA encoding the hepatitis C virus (HCV) envelope E2 protein modified the infection after challenge with homologous monoclonal HCV.  Hepatology. 2000;  32 618
    Search in Google Scholar
  • 15 Frank C. et al . The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt.  Lancet. 2000;  355 887
    Search in Google Scholar
  • 16 Fried M. et al . Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.  N Engl J Med. 2002;  347 975
    Search in Google Scholar
  • 17 Gordon S. et al . A phase II, 12-week study of ISIS 14 803, an antisense inhibitor of HCV for the treatment of chronic hepatitis C.  Hepatology. 2002;  36 795A
    Search in Google Scholar
  • 18 Hadzyannis S. Peginterferon alfa-2a (40KD) (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 of Hepatology. 2002;  36 3 (suppl 1)
    Search in Google Scholar
  • 19 Heathcote E. et al . Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis.  N Engl J Med. 2000;  343 1673
    Search in Google Scholar
  • 20 Heim M H, Moradpour D, Blum H E. Expression of hepatitis C virus proteins inhibits signal transduction through the Jak-STAT pathway.  J Virol. 1999;  73 8469
    Search in Google Scholar
  • 21 Higuchi R, Fockler C, Dollinger G, Watson R. Kinetic PCR analysis: real-time monitoring of DNA amplificationreactions.  Biotechnology. 1993;  11 1026
    Search in Google Scholar
  • 22 Hinrichsen H. et al . First report on the antiviral efficacy off BILN 2061, a novel oral HCV serine protease inhibitor, in patients with chronic hepatitis C genotype 1.  Hepatology. 2002;  36 866A
    Search in Google Scholar
  • 23 Hoofnagle J. Hepatitis C: the clinical spectrum of disease.  Hepatology. 1997;  26 15S (Suppl 1)
    Search in Google Scholar
  • 24 Iftikar R. et al . HCV RNA and immunological response to thymalfasin in combination with peginterferon alfa-2a in HCV non-responders: a 12-week kinetic study.  Hepatology. 2002;  36 790A
    Search in Google Scholar
  • 25 Inchauspé G. DNA vaccine strategies for hepatitis C.  J Hepatol. 1999;  30 339
    Search in Google Scholar
  • 26 Kammer A R. et al . Molecular mimicry of human cytochrome P450 by hepatitis C virus at the level of cytotoxic T cell recognition.  J Exp Med. 1999;  190 169
    Search in Google Scholar
  • 27 Kenny-Walsh E. The natural history of hepatitis C virus infection.  Clin Liver Dis. 2001;  5 969
    Search in Google Scholar
  • 28 Lai M E. et al . Hepatitis C virus in multiple episodes of acute hepatitis in polytransfused thalassaemic children.  Lancet. 1994;  343 388
    Search in Google Scholar
  • 29 Lawitz E. Pegylated Interferon Alfa 2b (PEG-IFN) and Ribavirin for Hepatitis C Patients who were Nonresponders to previous therapy.  Gastroenterology. 2002;  80 122
    Search in Google Scholar
  • 30 Lechmann M. et al . Hepatitis C virus-like particles induce virus-specific humoral and cellular immune responses in mice.  Hepatology. 2001;  34 417
    Search in Google Scholar
  • 31 Lesburg C ACM, Ferrari E, Hong Z, Mannarino A F, Weber P C. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site.  Nat Struct Biol. 1999;  6 937
    Search in Google Scholar
  • 32 Maertens G. et al . Improvement of chronic active hepatitis C in chronically infected chimpanzees after therapeutic vaccination with the HCV E1 protein.  Acta Gastroenterol Belg. 2000;  63 203
    Search in Google Scholar
  • 33 Manns M, Mc Hutchison J, Gordon S, Rustgi V. et al . Peginterferon alfa-2b plus ribavirin compared with interferonalfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial.  Lancet. 2001;  358 958
    Search in Google Scholar
  • 34 McHutchison J. et al . A 4-week trial of VX 497 (an IMPDH inhibitor) combined with interferon in previously untreated patients with chronic hepatitis C.  Hepatology. 2001;  36 329A
    Search in Google Scholar
  • 35 Memon M. Hepatitis C: an epidemiological review.  Viral Hepat. 2002;  9 84
    Search in Google Scholar
  • 36 Moradpour D. et al . Functional Properties of a Monoclonal Antibody Inhibiting the Hepatitis C Virus RNA-dependent RNA Polymerase.  JBC. 2002;  277 593
    Search in Google Scholar
  • 37 Narjes H, Yong C, Stähle H, Steinmann G. Tolerability and pharmacokinetics of BILN 2061, a novel HCV serine protease inhibitor, after oral single doses of 5 to 2400 mg in healthy male subjects.  Hepatology. 2002;  36 800A
    Search in Google Scholar
  • 38 Neumann A U. et al . Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy.  Science. 1998;  282 103
    Search in Google Scholar
  • 39 NIH & National Institutes of Health . Consensus development conference panel statement: management of hepatitis C.  Hepatology. 1997;  26 2S (Suppl 1))
    Search in Google Scholar
  • 40 Puro V, Petrosillo N, Ippolito G. Risk of hepatitis C seroconversion after occupational exposures in health care workers. Italian Study Group on Occupational Risk of HIV and Other Bloodborne Infections.  Am J Infect Control. 1995;  23 273
    Search in Google Scholar
  • 41 Ross R S. et al . Transmission of the hepatitis C virus from a patient to an anesthesiology assistant to five patients.  N Engl J Med. 2000;  343 1851
    Search in Google Scholar
  • 42 Sarrazin C, Teuber G, Kokka R, Rabenau H, Zeuzem S. Detection of residual hepatitis C virus RNA by transcription-mediated amplification in patients with complete virologic response according to polymerase chain reaction-based assays.  Hepatology. 2000;  32 818
    Search in Google Scholar
  • 43 Simmonds P. et al . A proposed system for the nomenclature of hepatitis C viral genotypes.  Hepatology. 1994;  19 1321
    Search in Google Scholar
  • 44 Takaki A. et al . Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C.  Nat Med. 2000;  6 578
    Search in Google Scholar
  • 45 Tanaka E. et al . Evaluation of a new enzyme immunoassay for hepatitis C virus (HCV) core antigen with clinical sensitivity approximating that of genomic amplification of HCV RNA.  Hepatology. 2000;  32 388
    Search in Google Scholar
  • 46 Thimme R, Spangenberg H C, von Weizsäcker F, Blum H E. T-Zell-Antwort bei Hepatitis B und C: von der Virus-elimination bis zum hepatozellulären Karzinom.  Dtsch Med Wochenschr. 2002;  127 2277
    Search in Google Scholar
  • 47 Tong M J, El-Farra N S, Reikes A R, Co R L. Clinical outcomes after transfusion-associated hepatitis C.  N Engl J Med. 1995;  332 1463
    Search in Google Scholar
  • 48 van Regenmortel M. et al .Virus Taxonomy. The VIIth Report of the International Committee on Taxonomy of Viruses. San Diego: Academic Press 2000
    Search in Google Scholar
  • 49 Vidalin O. et al . Use of conventional or replicating nucleic acid-based vaccines and recombinant Semliki forest virus-derived particles for the induction of immune responses against hepatitis C virus core and E2 antigens.  Virology. 2000;  276 259
    Search in Google Scholar
  • 50 Wasley A, Alter M J. Epidemiology of hepatitis C: geographic differences and temporal trends.  Semin Liver Dis. 2000;  20 1
    Search in Google Scholar
  • 51 WHO. Global surveillance and control of hepatitis C.  J Viral Hepat. 1999;  6 35
    Search in Google Scholar
  • 52 WHO. Hepatitis C - global prevalence (update).  Wkly Epidemiol Rec. 2000;  75 18
    Search in Google Scholar
  • 53 Wiese M, Berr F, Lafrenz M, Porst H. Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in germany: a 20-year multicenter study.  Hepatology. 2000;  32 91
    Search in Google Scholar
  • 54 Yao N, Reichert P, Taremi S S, Prosise W W, Weber P C. Molecular views of viral polyprotein processing revealed by the crystal structure of the hepatitis C virus bifunctional protease-helicase.  Structure Fold Des. 1999;  7 1353
    Search in Google Scholar
  • 55 Zeuzem S. et al . Peginterferon alfa-2a in patients with chronic hepatitis C.  N Engl J Med. 2000;  343 1666
    Search in Google Scholar
  • 56 Zignego A, Bréchot C. Extrahepatic manifestations of HCV infection: facts and controversies.  J Hepatol. 1999;  31 369
    Search in Google Scholar
  • 57 Zinkernagel R. Immunology taught by viruses.  Science. 1996;  271 173
    Search in Google Scholar

Prof. Dr. A. Cerny

Clinica Medica, Ospedale Civico

CH-6903 Lugano

Phone: ++41/91/8116046

Fax: ++41/91/8116045

Email: andreas.cerny@bluewin.ch