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  1. AU="Wohnsland, Anette"
  2. AU="Reed, K R"
  3. AU="Gnanapragasam, Vincent J"
  4. AU="Vutova, M"
  5. AU="Conley, Matthew"
  6. AU="Stark, Luisa S"
  7. AU="Dettman, David L"
  8. AU="Hassan, Zurina"
  9. AU="R.N. Singh"
  10. AU="Aibo Li"

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Artikel: Viral determinants of resistance to treatment in patients with hepatitis C.

Wohnsland, Anette / Hofmann, Wolf Peter / Sarrazin, Christoph

Clinical microbiology reviews

2007  Band 20, Heft 1, Seite(n) 23–38

Abstract: Chronic hepatitis C virus (HCV) infection affects more than 170 million persons worldwide and is responsible for the development of liver cirrhosis in many cases. Standard treatment with pegylated alpha interferon (IFN-alpha) in combination with the ... ...

Abstract Chronic hepatitis C virus (HCV) infection affects more than 170 million persons worldwide and is responsible for the development of liver cirrhosis in many cases. Standard treatment with pegylated alpha interferon (IFN-alpha) in combination with the nucleoside analogue ribavirin leads to a sustained virologic response in approximately half of the patients. IFN-alpha is classified as an indirect treatment, as it interacts with the host's immune response. The mechanism of action of ribavirin is still unknown. The benefit of triple therapy by adding other antiviral agents, e.g., amantadine, is controversial. Currently, new direct antiviral drugs (HCV protease/polymerase inhibitors) are being evaluated in phase 1/phase 2 trials. Phenotypic resistance to antiviral therapy has been attributed to amino acid variations within distinct regions of the HCV polyprotein. While sensitivity to IFN-alpha-based antiviral therapy in vivo is clearly correlated with the number of mutations within the HCV NS5A protein, the underlying functional mechanisms for this association are unknown. In turn, in vitro, several mechanisms to circumvent the host immune defense or to block treatment-induced antiviral activities have been described for different HCV proteins. By the introduction of direct antiviral drugs, hepatitis C therapy now is entering a new era in which the development of resistance may become the most important parameter for treatment success or failure.
Mesh-Begriff(e) Amantadine/pharmacology ; Amantadine/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Drug Resistance, Viral/genetics ; Drug Resistance, Viral/physiology ; Hepacivirus/drug effects ; Hepatitis C/drug therapy ; Hepatitis C/virology ; Humans ; Interferon-alpha/pharmacology ; Interferon-alpha/therapeutic use ; Ribavirin/pharmacology ; Ribavirin/therapeutic use
Chemische Substanzen Antiviral Agents ; Interferon-alpha ; Ribavirin (49717AWG6K) ; Amantadine (BF4C9Z1J53)
Sprache Englisch
Erscheinungsdatum 2007-01
Erscheinungsland United States
Dokumenttyp Journal Article ; Review
ZDB-ID 645015-5
ISSN 1098-6618 ; 0893-8512
ISSN (online) 1098-6618
ISSN 0893-8512
DOI 10.1128/CMR.00010-06
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Zs.A 2409: Hefte anzeigen Standort:
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