Chapter 14 : Clinical Aspects of Hepatitis C Virus Infection

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Clinical Aspects of Hepatitis C Virus Infection, Page 1 of 2

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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.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14

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Image of Figure 1.
Figure 1.

Natural history of hepatitis C infection.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 2.
Figure 2.

Evolution of SVR with different therapies during the past decade.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 3.
Figure 3.

The main types of treatment response in chronic hepatitis C. (A) SVR; (B) virologic response followed by a relapse; (C) virologic nonresponse.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 4.
Figure 4.

SVR in phase III trials of pegIFN-α2a with and without ribavirin (RBV) (A) or pegIFN-α2b with or without ribavirin (B).

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 5.
Figure 5.

Importance of monitoring early virologic response during treatment of genotype 1 infection patients with respect to outcome. W, week.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 6.
Figure 6.

SVR rates following treatment with pegIFN-α and ribavirin in difficult-to-treat populations.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 7.
Figure 7.

Future concept of anti-HCV therapy. DMPK, drug metabolism and pharmacokinetic profile.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Table 1.

Host and viral factors associated with SVR

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Table 2.

Main side effects of pegIFN and ribavirin

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Table 3.

Protease and polymerase inhibitors still in clinical trials or cancelled

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14

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