A Polymorphism Near IL28B Is Associated With Spontaneous Clearance of Acute Hepatitis C Virus and Jaundice

Tillmann, Hans L.; Thompson, Alex; Patel, Keyur; Wiese, Manfred; Tenckhoff, H; Nischalke, Hans Dieter; Lokhnygina, Yuliya; Kullig, U.; Göbel, U.; Capka, E.; Wiegand, Johannes; Schiefke, Ingolf; Güthoff, W.; Grüngreiff, Kurt; König, I.; Spengler, Ulrich; McCarthy, Jeanette; Shianna, Kevin V.; Goldstein, David B.; McHutchison, John G.; Timm, Jörg; Nattermann, Jacob

doi:10.1053/j.gastro.2010.07.005

Cited by 285 publications

(221 citation statements)

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“…[12] and with spontaneous virus clearance [9]. In our group of untreated patients we found a significant association with a higher inflammatory activity grade for the rs8099917 TT genotype.…”

Section: Discussionsupporting

confidence: 53%

IL28B SNPs rs12979860 and rs8099917 Are Associated with Inflammatory Response in Argentine Chronic HCV Patients

Machicote¹,

Flichmann²,

Arana³

et al. 2018

IJCM

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Background: Hepatitis C virus (HCV) is a major cause of chronic liver disease, including cirrhosis and liver cancer. The aim of our study was to determine whether IL28B single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 can be considered a prognostic host factor in untreated chronic HCV patients. Methods: We set up a real-time Allele Specific PCR amplification to determine the allele present in each polymorphic site, and statistically grouped and compared this result with clinical data. Results: We determined rs12979860 and rs8099917 genotype and allele frequencies in a single cohort of untreated chronically HCV-infected patients. We found significant associations between higher inflammatory activity, measured as ALT levels or METAVIR scores and rs12979860 CC (P = 0.0013 and P = 0.0033, respectively) and rs8099917 TT (P = 0.0005 and P = 0.0264, respectively) genotypes. Interestingly, considering both genotypes together, we also found association with ALT levels (P = 0.0003; OR = 5.125) or METAVIR scores (P = 0.0038; OR = 5.179), suggesting and additive effect on liver inflammation in these patients. Conclusion: we show association between hepatic inflammatory activity in a single Argentinean untreated chronically HCV cohort and SNPs located in the interferon lambda gene region. The studied polymorphisms, together with further innate and adaptive immune responses, clearly play a role in modulating the HCV infected patients outcome, contributing to hepatic inflammation and possible fibrosis/cirrhosis.

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Section: Discussionsupporting

confidence: 53%

IL28B SNPs rs12979860 and rs8099917 Are Associated with Inflammatory Response in Argentine Chronic HCV Patients

Machicote¹,

Flichmann²,

Arana³

et al. 2018

IJCM

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“…Meanwhile, 80% of patients who carry 2 copies of this advantageous variant clear the virus during IFN therapy and remain virus-free with a sustained viral response. This mutation is more common in Caucasian and Asian populations, whereas it is only found in 40-50% of sub-Saharan Africans who are known to be more resistant to combination therapy (Thomas et al, 2009;Montes-Cano et al, 2010;Tillmann et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Association of the interleukin-28B gene polymorphism with development of hepatitis virus-related hepatocellular carcinoma and liver cirrhosis: a meta-analysis

Suo¹,

Zhao²

2013

Genet. Mol. Res.

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ABSTRACT. We examined the association of the interleukin-28B (IL-28B) gene rs12979860 T/C polymorphism with development of hepatitis virus-related hepatocellular car cinoma (HCC) and liver cirrhosis (LC). Two investigators independently searched the PubMed, Elsevier, EMBASE, Web of Science, Wiley Online Library, and Chinese National Knowledge Infrastructure data bases. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) for rs12979860 and HCC/LC were cal culated in a fixed-effect model (the Mantel-Haenszel method) and a random-effect model (the DerSimonian and Laird method) when appropriate. This meta-analysis included 7 eligible studies, with 1152 HCC and/or LC cases and 1326 controls. Overall, the rs12979860 T/C polymorphism was significantly as sociated with risk of hepatitis virusrelated HCC and LC development (TT vs CC+CT, pooled OR = 1.597, 95%CI = 1.254-2.036). When they were grouped by type of hepatitis virus, similar results were found for hepatitis C virus-related groups (TT vs CC+CT, pooled OR = 1.732, 95%CI = 1.343-2.235, P value < 0.0001). In the overall analysis, the IL-28B rs12979860 T/C polymorphism was 3709 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (3): 3708-3717 (2013) 28B gene polymorphism and hepatocellular cancer identified as a genetic risk factor for hepatitis virus-related HCC and LC development. A significant increase in the frequency of the T/T genotype was detected from chronic hepatitis to HCC and LC.

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“…[4][5][6] Further evidence that rs12979860 and rs8099917 SNPs of the IL28B locus are associated with spontaneous clearance is provided by cohorts of Swiss, Spanish, Australian and German patients with acute HCV infection followed during the course of hepatitis. [7][8][9][10] Few data are available on the association between IL28B SNPs and severity of liver fibrosis or presence of cirrhosis, and, in any case, these remain controversial. [11][12][13] We studied the relations of host genetic patterns of the IL28B locus (rs12979860 and rs8099917 SNPs), viral factors (positivity of serum HCV-RNA and HCV genotype), and liver iron overload, with spontaneous HCV clearance, severity of liver fibrosis, and SVR to interferon in a large, ethnically homogeneous cohort of thalassemia major (TM) patients with HCV infection.…”

Section: Il28b Polymorphisms Influence Stage Of Fibrosis and Spontanementioning

confidence: 99%

“…Analysis of the IL28B genotype effect according to a recessive model was pre-planned, based on previous results. [2][3][4][5][6][7][8][9][10] Multiple logistic regression models were used to assess the relationships among genetic (rs12979860 and rs8099917 SNPs), demographics (age and gender), and histological (classes of liver fibrosis and the liver iron concentration) features and spontaneous clearance of HCV, evidence of severe liver fibrosis, and response to antiviral therapy. Variables with a threshold value of P=0.1 at univariate analysis were included in the model, and variables with a threshold value of P≤0.05 were considered significant in the final model.…”

Section: Statisticsmentioning

confidence: 99%

IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection

et al. 2011

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We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 thalassemia major patients with hepatitis C virus infection. ResultsNinety-eight patients (40%) had a spontaneous viral clearance while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; P=0.008) or C/C genotype of rs12979860 polymorphism (OR 2.425; P=0.001). During observation, 131 patients with chronic infection underwent a liver biopsy; age (OR 1.058; P=0.01) G/T or G/G genotypes of rs8099917 polymorphism (OR 3.962; P=0.001), and C/T or T/T genotypes of rs12979860 polymorphism (OR 3.494; P=0.005) were associated with severe liver fibrosis, independent of liver iron concentration. Finally, T/T genotype of rs8099917 polymorphism (OR 3.014; P=0.03) or C/C genotype of rs12979860 polymorphism (OR 3.285; P=0.01), age (OR 0.902; P=0.001), female gender (OR 3.418; P=0.01) and 2 or 3 virus C genotypes (OR 4.700; P=0.007) were independently associated with sustained virological response in 114 patients treated with alpha-interferon . ConclusionsPolymorphisms in the interleukin-28B are associated with the control of hepatitis C virus infection in thalassemia major patients, and understanding allelic patterns has an important role in determining prognosis and therapeutic management.Key words: thalassemia major, hepatitis C virus, IL28b polymorphisms, spontaneous viral clearance, liver fibrosis, cirrhosis, interferon, sustained virological response. Haematologica 2012;97(5):679-686. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Di Marco V, Bronte F, Calvaruso V, Capra M, Borsellino Z, Maggio A, Renda MC, Pitrolo L, Lo Pinto MC, Rizzo M, Fiorenza F, Gerardi C, Grimaudo S, Di Cristina A, Levrero M, and Craxì A. IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection. IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection

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A Polymorphism Near IL28B Is Associated With Spontaneous Clearance of Acute Hepatitis C Virus and Jaundice

Cited by 285 publications

References 21 publications

IL28B SNPs rs12979860 and rs8099917 Are Associated with Inflammatory Response in Argentine Chronic HCV Patients

IL28B SNPs rs12979860 and rs8099917 Are Associated with Inflammatory Response in Argentine Chronic HCV Patients

Association of the interleukin-28B gene polymorphism with development of hepatitis virus-related hepatocellular carcinoma and liver cirrhosis: a meta-analysis

IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection

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