IL28B polymorphisms, IP-10 and viral load predict virological response to therapy in chronic hepatitis C

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2011.04635.x/abstract

IL28B polymorphisms, IP-10 and viral load predict virological response to

therapy in chronic hepatitis C

G. Fattovich1,2, L. Covolo3, S. Bibert4, G. Askarieh5, M. Lagging5, S.

Clément2, G. Malerba6, M. Pasino1, M. Guido7, M. Puoti8, G. B. Gaeta9, T.

Santantonio10, G. Raimondo11, R. Bruno12, P.-Y. Bochud4, F. Donato3, F.

Negro2,13, on behalf of the ITAHEC Study Group

Article first published online: 28 MAR 2011

DOI: 10.1111/j.1365-2036.2011.04635.x

© 2011 Blackwell Publishing Ltd

Issue

Alimentary Pharmacology & Therapeutics

Volume 33, Issue 10, pages 1162–1172, May 2011

Summary

Background  Hepatitis C virus (HCV) is a major cause of chronic liver disease,

cirrhosis and hepatocellular carcinoma and the identification of the predictors

of response to antiviral therapy is an important clinical issue.

Aim  To determine the independent contribution of factors including IL28B

polymorphisms, IFN-gamma inducible protein-10 (IP-10) levels and the homeostasis

model assessment of insulin resistance (HOMA-IR) score in predicting response to

therapy in chronic hepatitis C (CHC).

Methods  Multivariate analysis of factors predicting rapid (RVR) and sustained

(SVR) virological response in 280 consecutive, treatment-naive CHC patients

treated with peginterferon alpha and ribavirin in a prospective multicentre

study.

Results  Independent predictors of RVR were HCV RNA <400 000 IU/mL (OR 11.37;

95% CI 3.03–42.6), rs12980275 AA (OR 7.09; 1.97–25.56) and IP-10 (OR 0.04;

0.003–0.56) in HCV genotype 1 patients and lower baseline

γ-glutamyl-transferase levels (OR = 0.02; 0.0009–0.31) in HCV genotype 3

patients. Independent predictors of SVR were rs12980275 AA (OR 9.68;

3.44–27.18), age <40 years (OR = 4.79; 1.50–15.34) and HCV RNA <400 000

IU/mL (OR 2.74; 1.03–7.27) in HCV genotype 1 patients and rs12980275 AA (OR =

6.26; 1.98–19.74) and age <40 years (OR 5.37; 1.54–18.75) in the 88 HCV

genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV

genotype 1 patients (OR 33.0; 4.06–268.32) and the only independent predictor

of SVR in HCV genotype 2 (OR 9.0, 1.72–46.99) or genotype 3 patients (OR 7.8,

1.43–42.67).

Conclusions  In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and

IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA

level and age may yield more accurate pre-treatment prediction of SVR. HOMA-IR

score is not associated with viral response.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2011.04635.x/abstract

IL28B polymorphisms, IP-10 and viral load predict virological response to

therapy in chronic hepatitis C

G. Fattovich1,2, L. Covolo3, S. Bibert4, G. Askarieh5, M. Lagging5, S.

Clément2, G. Malerba6, M. Pasino1, M. Guido7, M. Puoti8, G. B. Gaeta9, T.

Santantonio10, G. Raimondo11, R. Bruno12, P.-Y. Bochud4, F. Donato3, F.

Negro2,13, on behalf of the ITAHEC Study Group

Article first published online: 28 MAR 2011

DOI: 10.1111/j.1365-2036.2011.04635.x

© 2011 Blackwell Publishing Ltd

Issue

Alimentary Pharmacology & Therapeutics

Volume 33, Issue 10, pages 1162–1172, May 2011

Summary

Background  Hepatitis C virus (HCV) is a major cause of chronic liver disease,

cirrhosis and hepatocellular carcinoma and the identification of the predictors

of response to antiviral therapy is an important clinical issue.

Aim  To determine the independent contribution of factors including IL28B

polymorphisms, IFN-gamma inducible protein-10 (IP-10) levels and the homeostasis

model assessment of insulin resistance (HOMA-IR) score in predicting response to

therapy in chronic hepatitis C (CHC).

Methods  Multivariate analysis of factors predicting rapid (RVR) and sustained

(SVR) virological response in 280 consecutive, treatment-naive CHC patients

treated with peginterferon alpha and ribavirin in a prospective multicentre

study.

Results  Independent predictors of RVR were HCV RNA <400 000 IU/mL (OR 11.37;

95% CI 3.03–42.6), rs12980275 AA (OR 7.09; 1.97–25.56) and IP-10 (OR 0.04;

0.003–0.56) in HCV genotype 1 patients and lower baseline

γ-glutamyl-transferase levels (OR = 0.02; 0.0009–0.31) in HCV genotype 3

patients. Independent predictors of SVR were rs12980275 AA (OR 9.68;

3.44–27.18), age <40 years (OR = 4.79; 1.50–15.34) and HCV RNA <400 000

IU/mL (OR 2.74; 1.03–7.27) in HCV genotype 1 patients and rs12980275 AA (OR =

6.26; 1.98–19.74) and age <40 years (OR 5.37; 1.54–18.75) in the 88 HCV

genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV

genotype 1 patients (OR 33.0; 4.06–268.32) and the only independent predictor

of SVR in HCV genotype 2 (OR 9.0, 1.72–46.99) or genotype 3 patients (OR 7.8,

1.43–42.67).

Conclusions  In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and

IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA

level and age may yield more accurate pre-treatment prediction of SVR. HOMA-IR

score is not associated with viral response.