Profound week 4 interferon responsiveness is mandatory for hepatitis C genotype 1 patients with unfavorable IL-28B genotype.

Abstract

BACKGROUND:

Viral kinetics and host interleukin 28B (IL-28B) genotype determine treatment outcome in hepatitis C virus genotype 1 (HCV-1) infection.

OBJECTIVES:

We aimed to explore the interplay between interferon responsiveness at treatment week 4 and IL28B genotype in the achievement of a sustained virological response (SVR; undetectable HCV RNA 24-weeks after end-of-treatment).

STUDY DESIGNS:

Rs8099917 genotypes were determined in 528 HCV-1 patients with peginterferon/ribavirin. Interferon responsiveness were evaluated by the degree of week 4 viral reduction: <1 log(10) IU/mL, 1-2 logs(10) IU/mL, 2-3 logs(10) IU/mL, 3-4 logs(10) IU/mL and ≥4 logs(10) IU/mL reduction and/or undetectable HCV RNA, respectively.

RESULTS:

The SVR rate was significantly higher in patients with great interferon responsiveness at week 4. A great interferon responsiveness was associated with younger age (P < 0.0001), lower body mass index (P = 0.0056), lower aspartate aminotransferase levels (P = 0.0009), higher hemogloblin concentration (P = 0.0033), higher platelet counts (P < 0.0001), male gender (P < 0.0001) and rs809997 TT-genotype (P < 0.0001). Comparing to non-TT genotype patients, TT genotype patients had a significantly higher SVR rate with moderate viral reduction (1-3 logs(10) IU/mL) at week 4 (58.9% vs. 18.2%, P < 0.001), and the SVR rate did not differ between TT/non-TT patients on the extreme ends (<1 or >3 log(10) IU/mL reduction) of week 4 interferon responsiveness. For non-TT genotype carriers who were with <3 logs(10) reduction, none (0/15) could have a complete early virological response and only 10.9% (7/64) of the patients had an SVR.

CONCLUSIONS:

More profound interferon responsiveness is mandatory for HCV-1 patients with unfavorable IL-28B genotype.

• Authors: Chung-Feng Huang, Ming-Lung Yu, Jia-Horng Kao, Tai-Chung Tseng, Ming-Lun Yeh, Jee-Fu Huang, Chia-Yen Dai, Zu-Yau Lin, Shinn-Cherng Chen, Liang-Yen Wang, Suh-Hang Hank Juo, Wan-Long Chuang, Chen-Hua Liu
• Journal: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology (J Clin Virol) Vol. 56 Issue 4 Pg. 293-8 (Apr 2013) ISSN: 1873-5967 [Electronic] Netherlands
• PMID: 23246359 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Hemoglobins
• interferon-lambda, human
• Interferon alpha-2
• Interferon-alpha
• Interleukins
• RNA, Viral
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• Interferons
• Aspartate Aminotransferases
• peginterferon alfa-2b
• peginterferon alfa-2a

Topics

• Adult
• Age Factors
• Aged
• Antiviral Agents (administration & dosage, pharmacology)
• Aspartate Aminotransferases (analysis)
• Body Mass Index
• Drug Therapy, Combination
• Female
• Genetic Testing
• Genotype
• Hemoglobins (analysis)
• Hepacivirus (genetics, pathogenicity)
• Hepatitis C, Chronic (drug therapy, virology)
• Heterozygote
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage, pharmacology)
• Interferons
• Interleukins (genetics)
• Male
• Middle Aged
• Platelet Count
• Polyethylene Glycols (administration & dosage, pharmacology)
• RNA, Viral (genetics, metabolism)
• Recombinant Proteins (administration & dosage, pharmacology)
• Ribavirin (administration & dosage, pharmacology)
• Sex Factors
• Time Factors
• Treatment Outcome