Very early viral kinetics on interferon treatment in chronic hepatitis C virus genotype 4 infection.
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).


CONCLUSIONS
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.
Jessner
Wolfgang
W
Department of Internal Medicine III, Gastroenterology and Hepatology, Vienna Medical University, Vienna, Austria.
Gschwantler
Michael
M
Formann
Elisabeth
E
Gurguta
Calin
C
Watkins-Riedel
Thomas
T
Wrba
Friedrich
F
Ferenci
Peter
P
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a