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Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load
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Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load
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Journal Article
Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load
2012
Overview
Background
This study explores pretreatment predictive factors for ultimate virological responses to pegylated interferon-α (1.5 μg/kg/week) and ribavirin (600–1000 mg/day) (PEG-IFN/RBV) combination therapy for patients infected with hepatitis C virus (HCV)-1b and a high viral load.
Methods
A total of 75 patients underwent PEG-IFN/RBV combination therapy for 48 weeks. HCV amino acid (aa) substitutions in non-structural protein 5a, including those in the IFN/RBV resistance-determining region (IRRDR) and the IFN sensitivity-determining region and the core regions, as well as the genetic variation (rs8099917) near the interleukin 28B (IL28B) gene (genotype TT) were analyzed.
Results
Of the 75 patients, 49 % (37/75) achieved a sustained virological response (SVR), 27 % (20/75) showed relapse, and 24 % (18/75) showed null virological response (NVR). Multivariate logistic regression analysis identified IRRDR with 6 or more mutations (IRRDR ≥6) [odds ratio (OR) 11.906,
p
< 0.0001] and age <60 years (OR 0.228,
p
= 0.015) as significant determiners of SVR and IL28B minor (OR 14.618,
p
= 0.0019) and platelets <15 × 10
4
/mm
3
(OR 0.113,
p
= 0.0096) as significant determiners of NVR. A combination of IRRDR ≥6 and age <60 years improved SVR predictability (93.3 %), and that of IRRDR ≤5 and age ≥60 years improved non-SVR predictability (84.0 %). Similarly, a combination of IL28B minor and platelets <15 × 10
4
/mm
3
improved NVR predictability (85.7 %), and that of IL28B major and platelets ≥15 × 10
4
/mm
3
improved non-NVR (response) (97.1 %) predictability.
Conclusion
IRRDR ≥6 and age <60 years were significantly associated with SVR. IL28B minor and platelets <15 × 10
4
/mm
3
were significantly associated with NVR. Certain combinations of these factors improved SVR and NVR predictability and could, therefore, be used to design therapeutic strategies.
Publisher
Springer Japan,Springer Nature B.V
Subject
/ Adult
/ Age
/ Aged
/ Antiviral Agents - administration & dosage
/ Antiviral Agents - therapeutic use
/ Female
/ Genotype
/ Hepatitis C, Chronic - drug therapy
/ Hepatitis C, Chronic - genetics
/ Hepatitis C, Chronic - virology
/ Humans
/ Interferon-alpha - administration & dosage
/ Interferon-alpha - therapeutic use
/ Male
/ Medicine
/ Mutation
/ Pancreas
