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Chapter 14 : Clinical Aspects of Hepatitis C Virus Infection
Category: Viruses and Viral Pathogenesis; Clinical Microbiology
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Recently, the most significant progress in knowledge of hepatitis C virus (HCV) biology and interaction with host cells has concerned the role of lipids for genome replication, assembly and egress, and entry into cells. The major hepatic consequence of HCV infection is the progression to cirrhosis and its complications, such as ascites, hepatic insufficiency, and hepatocellular carcinoma (HCC). With the identification in 1989 of HCV as the infectious agent responsible for non-A/non-B hepatitis and the development of specific detection tests, it has become possible to monitor the efficacy of interferon (IFN)-α treatment. With the increased survival associated with the use of highly active antiretroviral therapy (HAART), morbidity and mortality from HCV-induced liver disease have started to increase significantly. Microarray results from liver biopsy tissue taken before therapy in a cohort of patients given pegIFN and ribavirin were recently reported. In this study, patients who were subsequently identified as non-responders had high baseline expression of IFN-stimulated genes (ISGs), whereas responders to therapy more closely resembled healthy controls. Kempf et al. illustrated the need for good knowledge of drug metabolism to improve the efficacy of a drug in vivo. In this study it was shown that a pharmacokinetic enhancement of telaprevir and boceprevir could be achieved by codosing with ritonavir, a potent inhibitor of the cytochrome P450 3A, which is involved in the metabolism of both drugs.
Key Concept Ranking
- Major Histocompatibility Complex Class I
Natural history of hepatitis C infection.
Evolution of SVR with different therapies during the past decade.
The main types of treatment response in chronic hepatitis C. (A) SVR; (B) virologic response followed by a relapse; (C) virologic nonresponse.
SVR in phase III trials of pegIFN-α2a with and without ribavirin (RBV) (A) or pegIFN-α2b with or without ribavirin (B).
Importance of monitoring early virologic response during treatment of genotype 1 infection patients with respect to outcome. W, week.
SVR rates following treatment with pegIFN-α and ribavirin in difficult-to-treat populations.
Future concept of anti-HCV therapy. DMPK, drug metabolism and pharmacokinetic profile.
Host and viral factors associated with SVR
Main side effects of pegIFN and ribavirin
Protease and polymerase inhibitors still in clinical trials or cancelled