Document Detail

Very early viral kinetics on interferon treatment in chronic hepatitis C virus genotype 4 infection.
MedLine Citation:
PMID:  18672537     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Interferon (IFN)-resistant hepatitis C virus strains limit efficacy of antiviral combination therapy in patients infected with genotypes 1 and 4. A single test dose of IFN was useful to identify non-responders to IFN-alpha2b/ribavirin (RBV) or likely non-responders to pegylated (PEG)-IFN-alpha2a/RBV therapy in genotype 1 patients. Our aim was to investigate this approach in genotype 4 patients. METHODS: Viral load was measured in 46 patients before and 24 h after 10 megaunits (MU) IFN-alpha2b, and before and during 2 weeks of daily 5 MU IFN-alpha2b administration. Thereafter, patients received 48 weeks combination therapy with either 180 microg PEG-IFN-alpha2a/week (n=33), 1.5 microg/kg PEG-IFN-alpha2b/week (n=7) or 5 MU IFN-alpha2b/2 days (n=6), along with 1-1.2g RBV/day. For prediction analysis the largest group (PEG-IFN-alpha2a) was evaluated only. RESULTS: Median 24 h log10 change after 10 MU IFN-alpha2b was 1.15 (range 0.08-2.48) and after 5 MU IFN-alpha2b was 0.81 (-0.12-2.22; P<0.0001). Log10 changes after 2 weeks on 5 MU IFN-alpha2b daily and 24 h after 10 MU were the best predictors of early virological response (defined by negativity of a standard qualitative PCR) to PEG-IFN-alpha2a/RBV combination therapy (area under curve [AUC]=0.97; P<0.001, receiver operating characteristics), 24 h log10 change after 10 MU was the best predictor of sustained virological response (SVR; AUC=0.91, P=0.001). CONCLUSION: As in genotype 1 patients, there is large variation in IFN responsiveness, including the presence of resistant strains, in genotype 4 patients. A 24 h log10 change after 10 MU IFN-alpha2b is an excellent predictor of SVR on PEG-IFNalpha2a/RBV combination therapy. This test may be useful to obtain homogeneous groups for clinical studies and could help in clinical decision making.
Wolfgang Jessner; Michael Gschwantler; Elisabeth Formann; Calin Gurguta; Thomas Watkins-Riedel; Friedrich Wrba; Peter Ferenci
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Antiviral therapy     Volume:  13     ISSN:  1359-6535     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  2008  
Date Detail:
Created Date:  2008-08-04     Completed Date:  2008-09-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  581-9     Citation Subset:  IM    
Department of Internal Medicine III, Gastroenterology and Hepatology, Vienna Medical University, Vienna, Austria.
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MeSH Terms
Antiviral Agents* / pharmacology,  therapeutic use
Drug Therapy, Combination
Hepacivirus* / classification,  drug effects,  genetics,  physiology
Hepatitis C, Chronic / drug therapy*,  virology
Interferon Alfa-2a* / administration & dosage,  therapeutic use
Interferon Alfa-2b* / administration & dosage,  therapeutic use
Middle Aged
Polyethylene Glycols* / administration & dosage,  therapeutic use
RNA, Viral / blood
Ribavirin* / administration & dosage,  therapeutic use
Time Factors
Treatment Outcome
Viral Load
Reg. No./Substance:
0/Antiviral Agents; 0/Polyethylene Glycols; 0/RNA, Viral; 0/peginterferon alfa-2a; 0/peginterferon alfa-2b; 36791-04-5/Ribavirin; 76543-88-9/Interferon Alfa-2a; 99210-65-8/Interferon Alfa-2b

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