Complementary role of vitamin D deficiency and the interleukin-28B rs12979860 C/T polymorphism in predicting antiviral response in chronic hepatitis C

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Hepatology. 2011 Apr;53(4):1118-26. doi: 10.1002/hep.24201.

Complementary role of vitamin D deficiency and the interleukin-28B rs12979860

C/T polymorphism in predicting antiviral response in chronic hepatitis C.

Bitetto D, Fattovich G, Fabris C, Ceriani E, Falleti E, Fornasiere E, Pasino M,

Ieluzzi D, Cussigh A, Cmet S, Pirisi M, Toniutto P.

Department of Medicine and Pathology Clinical and Experimental, Medical Liver

Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy.

Abstract

The widely accepted interleukin-28B (IL-28B) rs12979860 C/T polymorphism and the

more recently proposed vitamin D serum concentration are two novel predictors of

the response to antiviral treatment in chronic hepatitis C virus (HCV)

infection. This study aimed to verify whether the IL-28B rs12979860 C/T

polymorphism and pretreatment serum vitamin D levels have independent or

complementary roles in predicting the rates of sustained viral response (SVR).

The present study included 211 consecutive, treatment-naïve chronic HCV

patients who had their pretreatment serum 25-OH vitamin D level and IL-28B

rs12979860 C/T genotype determined. Overall, SVR was achieved by 134/211 (63.5%)

patients and by 47/110 (42.7%) patients infected with difficult-to-treat HCV

genotypes. On multivariate analysis, SVR was predicted by the HCV genotype, the

IL-28B rs12979860 C/T polymorphism, and gamma-glutamyl transpeptidase, HCV RNA,

cholesterol, and 25-OH vitamin D serum levels, with an area under the receiver

operating characteristic (ROC) curve of 0.827. When difficult-to-treat HCV

genotypes were analyzed separately, the SVR was predicted by the IL-28B

rs12979860 C/T polymorphism, viral load, and serum vitamin D level, with an area

under the ROC curve of 0.836. Moreover, by categorizing these latter patients

into four groups-C/C homozygotes with vitamin D levels >20 ng/mL (group A) or

≤20 ng/mL (group and C/T heterozygotes or T/T homozygotes with vitamin D

levels >20 ng/mL (group C) or ≤20 ng/mL (group D)-a significant linear trend

was observed, with SVR rates in the following descending order: group A, 18/21

(85.7%); group B, 6/11 (54.5%); group C, 14/38 (36.8%); and group D, 9/40

(22.5%) (P < 0.0001). Conclusion: Vitamin D serum levels are complementary to

the IL-28B rs12979860 C/T polymorphism in enhancing the correct prediction of

the SVR in treatment-naïve chronic hepatitis C. (HEPATOLOGY 2011;).

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21480318 [PubMed - in process]

[Guest guest]

Hepatology. 2011 Apr;53(4):1118-26. doi: 10.1002/hep.24201.

Complementary role of vitamin D deficiency and the interleukin-28B rs12979860

C/T polymorphism in predicting antiviral response in chronic hepatitis C.

Bitetto D, Fattovich G, Fabris C, Ceriani E, Falleti E, Fornasiere E, Pasino M,

Ieluzzi D, Cussigh A, Cmet S, Pirisi M, Toniutto P.

Department of Medicine and Pathology Clinical and Experimental, Medical Liver

Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy.

Abstract

The widely accepted interleukin-28B (IL-28B) rs12979860 C/T polymorphism and the

more recently proposed vitamin D serum concentration are two novel predictors of

the response to antiviral treatment in chronic hepatitis C virus (HCV)

infection. This study aimed to verify whether the IL-28B rs12979860 C/T

polymorphism and pretreatment serum vitamin D levels have independent or

complementary roles in predicting the rates of sustained viral response (SVR).

The present study included 211 consecutive, treatment-naïve chronic HCV

patients who had their pretreatment serum 25-OH vitamin D level and IL-28B

rs12979860 C/T genotype determined. Overall, SVR was achieved by 134/211 (63.5%)

patients and by 47/110 (42.7%) patients infected with difficult-to-treat HCV

genotypes. On multivariate analysis, SVR was predicted by the HCV genotype, the

IL-28B rs12979860 C/T polymorphism, and gamma-glutamyl transpeptidase, HCV RNA,

cholesterol, and 25-OH vitamin D serum levels, with an area under the receiver

operating characteristic (ROC) curve of 0.827. When difficult-to-treat HCV

genotypes were analyzed separately, the SVR was predicted by the IL-28B

rs12979860 C/T polymorphism, viral load, and serum vitamin D level, with an area

under the ROC curve of 0.836. Moreover, by categorizing these latter patients

into four groups-C/C homozygotes with vitamin D levels >20 ng/mL (group A) or

≤20 ng/mL (group and C/T heterozygotes or T/T homozygotes with vitamin D

levels >20 ng/mL (group C) or ≤20 ng/mL (group D)-a significant linear trend

was observed, with SVR rates in the following descending order: group A, 18/21

(85.7%); group B, 6/11 (54.5%); group C, 14/38 (36.8%); and group D, 9/40

(22.5%) (P < 0.0001). Conclusion: Vitamin D serum levels are complementary to

the IL-28B rs12979860 C/T polymorphism in enhancing the correct prediction of

the SVR in treatment-naïve chronic hepatitis C. (HEPATOLOGY 2011;).

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21480318 [PubMed - in process]