Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients

Hiromi Abe, Hidenori Ochi, Toshiro Maekawa, C. Nelson Hayes, Masataka Tsuge, Daiki Miki, Fukiko Mitsui, Nobuhiko Hiraga, Michio Imamura, Shoichi Takahashi, Waka Ohishi, Koji Arihiro, Michiaki Kubo, Yusuke Nakamura, Kazuaki Chayama

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Abstract

Background & Aims: A common genetic variation at the IL28 locus has been found to affect the response of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. An allele associated with a favorable response (rs8099917 T), which is the major allele in the majority of Asian, American, and European populations, has also been found to be associated with spontaneous eradication of the virus. Methods: As no studies have yet analyzed the effect of the polymorphism on biochemical and inflammatory changes in chronic infection, we analyzed a cohort of patients with chronic hepatitis C (n = 364) for the effect of the IL28 polymorphism on viral, biochemical, and histological findings. Results: We found that the proportion of HCV wild type core amino acids 70 and 91 was significantly greater (p = 1.21 × 10-4 and 0.034) and levels of gamma-GTP significantly lower (p = 0.001) in patients homozygous for the IL28 major allele. We also found that inflammation activity and fibrosis of the liver were significantly more severe in patients homozygous for the IL28 major allele (p = 0.025 and 0.036, respectively). Although the higher gamma-GTP levels were also associated with higher inflammatory activity and fibrosis, multivariate analysis showed that only the IL28 allele polymorphism, sex, alcohol consumption, and liver fibrosis were independently associated with gamma-GTP levels (p = 0.001, 0.0003, 0.0013, and 0.0348, respectively). Conclusions: These results suggest that different cytokine profiles induced by the IL28 polymorphism resulted in different biochemical and inflammatory conditions during chronic HCV infection and contribute to the progression of liver diseases.

Original languageEnglish
Pages (from-to)439-443
Number of pages5
JournalJournal of Hepatology
Volume53
Issue number3
DOIs
Publication statusPublished - 01-09-2010

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Guanosine Triphosphate
Hepacivirus
Alleles
Inflammation
Chronic Hepatitis C
Liver
Virus Diseases
Liver Cirrhosis
Asian Americans
Ribavirin
Alcohol Drinking
Interferons
Liver Diseases
Fibrosis
Multivariate Analysis
Cytokines
Viruses
Amino Acids
Infection
Population

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Abe, Hiromi ; Ochi, Hidenori ; Maekawa, Toshiro ; Hayes, C. Nelson ; Tsuge, Masataka ; Miki, Daiki ; Mitsui, Fukiko ; Hiraga, Nobuhiko ; Imamura, Michio ; Takahashi, Shoichi ; Ohishi, Waka ; Arihiro, Koji ; Kubo, Michiaki ; Nakamura, Yusuke ; Chayama, Kazuaki. / Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients. In: Journal of Hepatology. 2010 ; Vol. 53, No. 3. pp. 439-443.
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title = "Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients",
abstract = "Background & Aims: A common genetic variation at the IL28 locus has been found to affect the response of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. An allele associated with a favorable response (rs8099917 T), which is the major allele in the majority of Asian, American, and European populations, has also been found to be associated with spontaneous eradication of the virus. Methods: As no studies have yet analyzed the effect of the polymorphism on biochemical and inflammatory changes in chronic infection, we analyzed a cohort of patients with chronic hepatitis C (n = 364) for the effect of the IL28 polymorphism on viral, biochemical, and histological findings. Results: We found that the proportion of HCV wild type core amino acids 70 and 91 was significantly greater (p = 1.21 × 10-4 and 0.034) and levels of gamma-GTP significantly lower (p = 0.001) in patients homozygous for the IL28 major allele. We also found that inflammation activity and fibrosis of the liver were significantly more severe in patients homozygous for the IL28 major allele (p = 0.025 and 0.036, respectively). Although the higher gamma-GTP levels were also associated with higher inflammatory activity and fibrosis, multivariate analysis showed that only the IL28 allele polymorphism, sex, alcohol consumption, and liver fibrosis were independently associated with gamma-GTP levels (p = 0.001, 0.0003, 0.0013, and 0.0348, respectively). Conclusions: These results suggest that different cytokine profiles induced by the IL28 polymorphism resulted in different biochemical and inflammatory conditions during chronic HCV infection and contribute to the progression of liver diseases.",
author = "Hiromi Abe and Hidenori Ochi and Toshiro Maekawa and Hayes, {C. Nelson} and Masataka Tsuge and Daiki Miki and Fukiko Mitsui and Nobuhiko Hiraga and Michio Imamura and Shoichi Takahashi and Waka Ohishi and Koji Arihiro and Michiaki Kubo and Yusuke Nakamura and Kazuaki Chayama",
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Abe, H, Ochi, H, Maekawa, T, Hayes, CN, Tsuge, M, Miki, D, Mitsui, F, Hiraga, N, Imamura, M, Takahashi, S, Ohishi, W, Arihiro, K, Kubo, M, Nakamura, Y & Chayama, K 2010, 'Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients', Journal of Hepatology, vol. 53, no. 3, pp. 439-443. https://doi.org/10.1016/j.jhep.2010.03.022

Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients. / Abe, Hiromi; Ochi, Hidenori; Maekawa, Toshiro; Hayes, C. Nelson; Tsuge, Masataka; Miki, Daiki; Mitsui, Fukiko; Hiraga, Nobuhiko; Imamura, Michio; Takahashi, Shoichi; Ohishi, Waka; Arihiro, Koji; Kubo, Michiaki; Nakamura, Yusuke; Chayama, Kazuaki.

In: Journal of Hepatology, Vol. 53, No. 3, 01.09.2010, p. 439-443.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients

AU - Abe, Hiromi

AU - Ochi, Hidenori

AU - Maekawa, Toshiro

AU - Hayes, C. Nelson

AU - Tsuge, Masataka

AU - Miki, Daiki

AU - Mitsui, Fukiko

AU - Hiraga, Nobuhiko

AU - Imamura, Michio

AU - Takahashi, Shoichi

AU - Ohishi, Waka

AU - Arihiro, Koji

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Chayama, Kazuaki

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Background & Aims: A common genetic variation at the IL28 locus has been found to affect the response of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. An allele associated with a favorable response (rs8099917 T), which is the major allele in the majority of Asian, American, and European populations, has also been found to be associated with spontaneous eradication of the virus. Methods: As no studies have yet analyzed the effect of the polymorphism on biochemical and inflammatory changes in chronic infection, we analyzed a cohort of patients with chronic hepatitis C (n = 364) for the effect of the IL28 polymorphism on viral, biochemical, and histological findings. Results: We found that the proportion of HCV wild type core amino acids 70 and 91 was significantly greater (p = 1.21 × 10-4 and 0.034) and levels of gamma-GTP significantly lower (p = 0.001) in patients homozygous for the IL28 major allele. We also found that inflammation activity and fibrosis of the liver were significantly more severe in patients homozygous for the IL28 major allele (p = 0.025 and 0.036, respectively). Although the higher gamma-GTP levels were also associated with higher inflammatory activity and fibrosis, multivariate analysis showed that only the IL28 allele polymorphism, sex, alcohol consumption, and liver fibrosis were independently associated with gamma-GTP levels (p = 0.001, 0.0003, 0.0013, and 0.0348, respectively). Conclusions: These results suggest that different cytokine profiles induced by the IL28 polymorphism resulted in different biochemical and inflammatory conditions during chronic HCV infection and contribute to the progression of liver diseases.

AB - Background & Aims: A common genetic variation at the IL28 locus has been found to affect the response of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. An allele associated with a favorable response (rs8099917 T), which is the major allele in the majority of Asian, American, and European populations, has also been found to be associated with spontaneous eradication of the virus. Methods: As no studies have yet analyzed the effect of the polymorphism on biochemical and inflammatory changes in chronic infection, we analyzed a cohort of patients with chronic hepatitis C (n = 364) for the effect of the IL28 polymorphism on viral, biochemical, and histological findings. Results: We found that the proportion of HCV wild type core amino acids 70 and 91 was significantly greater (p = 1.21 × 10-4 and 0.034) and levels of gamma-GTP significantly lower (p = 0.001) in patients homozygous for the IL28 major allele. We also found that inflammation activity and fibrosis of the liver were significantly more severe in patients homozygous for the IL28 major allele (p = 0.025 and 0.036, respectively). Although the higher gamma-GTP levels were also associated with higher inflammatory activity and fibrosis, multivariate analysis showed that only the IL28 allele polymorphism, sex, alcohol consumption, and liver fibrosis were independently associated with gamma-GTP levels (p = 0.001, 0.0003, 0.0013, and 0.0348, respectively). Conclusions: These results suggest that different cytokine profiles induced by the IL28 polymorphism resulted in different biochemical and inflammatory conditions during chronic HCV infection and contribute to the progression of liver diseases.

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U2 - 10.1016/j.jhep.2010.03.022

DO - 10.1016/j.jhep.2010.03.022

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SP - 439

EP - 443

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

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