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The Impact of IL28B Genotype and Liver Fibrosis on the Hepatic Expression of IP10, IFI27, ISG15, and MX1 and Their Association with Treatment Outcomes in Patients with Chronic Hepatitis C.

Domagalski K, Pawłowska M, Kozielewicz D, Dybowska D, Tretyn A, Halota W - PLoS ONE (2015)

Bottom Line: We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007).We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004).The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10.

View Article: PubMed Central - PubMed

Affiliation: Centre For Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Toruń, Poland.

ABSTRACT
The strong impact of interleukin 28B (IL28B) polymorphisms on sustained virological response (SVR) after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC) is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment. Differential expression of IP10, IFI27, ISG15, and MX1 genes was assessed from pretreatment liver biopsies using quantitative PCR. Histopathological evaluation of liver specimens was performed on the basis of the Scheuer's modified scale. We showed that hepatic IFI27, ISG15, and MX1 expression was lower in the IL28B CC 12979860 and TT rs8099917 groups than in the CT-TT rs12979860 and TG-GG rs8099917 groups (P < 0.001). We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007). We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004). Additionally, the expression levels of IP10, IFI27 and ISG15, but not MX1, were significantly higher in non-SVR patients than in SVR patients. The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10. Silencing of IP10 is positive and independent from IL28B prediction of SVR, which is strongly associated with liver fibrosis in CHC patients.

No MeSH data available.


Related in: MedlinePlus

Association between the hepatic expression of IP10, IFI27, ISG15, and MX1 with F0-1 and F2-4 fibrosis.The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels. Fibrosis stages are defined according to the modified Scheuer classification.
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pone.0130899.g002: Association between the hepatic expression of IP10, IFI27, ISG15, and MX1 with F0-1 and F2-4 fibrosis.The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels. Fibrosis stages are defined according to the modified Scheuer classification.

Mentions: To clarify the relationship between IL28B and ISG expression, we estimated the association between clinical characteristics and expression of the analyzed genes. In general, univariate analysis showed no relationship between any of the investigated genes and demographic (age at biopsy, gender) or clinical (inflammatory activity, steatosis, ALT, AST, and GGTP activity) variables, except for liver fibrosis. We found that IP10 expression significantly differs by the stage of liver fibrosis (P = 0.007). As shown in Fig 2, the F0-F1 patients had decreased expression of IP10 compared to the F2-F4 group. Kruskal-Wallis analysis for individual stages of fibrosis from F0 to F3 revealed that IP10 expression significantly increased with the progression of fibrosis (P = 0.030; Fig 3).


The Impact of IL28B Genotype and Liver Fibrosis on the Hepatic Expression of IP10, IFI27, ISG15, and MX1 and Their Association with Treatment Outcomes in Patients with Chronic Hepatitis C.

Domagalski K, Pawłowska M, Kozielewicz D, Dybowska D, Tretyn A, Halota W - PLoS ONE (2015)

Association between the hepatic expression of IP10, IFI27, ISG15, and MX1 with F0-1 and F2-4 fibrosis.The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels. Fibrosis stages are defined according to the modified Scheuer classification.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482747&req=5

pone.0130899.g002: Association between the hepatic expression of IP10, IFI27, ISG15, and MX1 with F0-1 and F2-4 fibrosis.The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels. Fibrosis stages are defined according to the modified Scheuer classification.
Mentions: To clarify the relationship between IL28B and ISG expression, we estimated the association between clinical characteristics and expression of the analyzed genes. In general, univariate analysis showed no relationship between any of the investigated genes and demographic (age at biopsy, gender) or clinical (inflammatory activity, steatosis, ALT, AST, and GGTP activity) variables, except for liver fibrosis. We found that IP10 expression significantly differs by the stage of liver fibrosis (P = 0.007). As shown in Fig 2, the F0-F1 patients had decreased expression of IP10 compared to the F2-F4 group. Kruskal-Wallis analysis for individual stages of fibrosis from F0 to F3 revealed that IP10 expression significantly increased with the progression of fibrosis (P = 0.030; Fig 3).

Bottom Line: We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007).We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004).The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10.

View Article: PubMed Central - PubMed

Affiliation: Centre For Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Toruń, Poland.

ABSTRACT
The strong impact of interleukin 28B (IL28B) polymorphisms on sustained virological response (SVR) after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC) is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment. Differential expression of IP10, IFI27, ISG15, and MX1 genes was assessed from pretreatment liver biopsies using quantitative PCR. Histopathological evaluation of liver specimens was performed on the basis of the Scheuer's modified scale. We showed that hepatic IFI27, ISG15, and MX1 expression was lower in the IL28B CC 12979860 and TT rs8099917 groups than in the CT-TT rs12979860 and TG-GG rs8099917 groups (P < 0.001). We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007). We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004). Additionally, the expression levels of IP10, IFI27 and ISG15, but not MX1, were significantly higher in non-SVR patients than in SVR patients. The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10. Silencing of IP10 is positive and independent from IL28B prediction of SVR, which is strongly associated with liver fibrosis in CHC patients.

No MeSH data available.


Related in: MedlinePlus