Interferon-lambda genotype and low serum low-density lipoprotein cholesterol levels in patients with chronic hepatitis C infection

Li, Josephine H.; Lao, Xiang Qian; Tillmann, Hans L.; Rowell, Jennifer; Patel, Keyur; Thompson, Alexander; Suchindran, Sunil; Muir, Andrew J.; Guyton, John R.; Gardner, Stephen D.; McHutchison, John G.; McCarthy, Jeanette

doi:10.1002/hep.23592

Cited by 110 publications

(96 citation statements)

References 48 publications

(60 reference statements)

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“…PEG-IFN/RBV), compared to those carrying the T allele (C/T and T/T genotypes). More recently, it has also been proposed that the poor response IL28B variants, in hepatitis C patients, are also associated with lower pretreatment low-density lipoprotein cholesterol levels, 17,18 hepatic steatosis, 18,19 and insulin resistance, 19 compared to the ''responder'' genotype. However, it is still unclear whether the genetic variation at the IL28B locus affects the severity and pace of the progression of liver disease.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in the interleukin -28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection

et al. 2011

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Polymorphisms in the interleukin-28B (IL28B) region are associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Nevertheless, it is unknown whether genetic variation at the IL28B locus influences the natural history of chronic HCV infection. Thus, we asked whether an association between IL28B polymorphisms and liver fibrosis progression existed. We studied 247 consecutive patients with chronic HCV, an accurate estimate of the date of infection, and a liver biopsy performed before any treatment. No patient had a history of alcohol abuse or coinfection with other viruses. We assessed the role of rs8099917 and rs12979860 polymorphisms and the effect of host and environmental factors on fibrosis progression. Blood transfusion (75%) was the main modality of infection. Median age at infection was 21 years, and median interval between infection and liver biopsy was 25 years. One hundred twenty-nine patients (52%) were infected by HCV-1, 74 (30%) by HCV-2, 34 (14%) by HCV-3, and 10 (4%) by HCV-4. Bridging fibrosis/cirrhosis (Ishak !4) was detected in 24% of patients. Age at infection had a marked effect on fibrosis progression by both a linear model and Cox proportionalhazard regression (P < 2E-16). A 12.1% increase in the hazard of advanced fibrosis was estimated for each additional year at infection, suggesting that this was the major explanatory variable in this cohort. Male gender (P < 0.05), HCV genotype 3 (P < 0.001) and steatosis (P < 0.05) were also associated with faster fibrosis progression. Conversely, the two IL28B polymorphisms had no impact on fibrosis progression. Conclusion: In HCV patients with a known date of infection, IL28B genotype was not associated with fibrosis progression rate or with the risk of developing advanced liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Genetic variation in the interleukin -28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection

et al. 2011

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“…Other groups have investigated the impact of IL28B host polymorphisms on lipid metabolism in patients with chronic HCV infection and noted an association of the responder genotype with higher levels of total cholesterol, apo-lipoprotein B, and low-density lipoprotein (LDL) [19]. In the context of liver transplantation, Eurich et al [20] have reported that rs8099917 influences the biochemical and histological levels of graft inflammation, though not the progression to fibrosis in patients with recurrent HCV infection post-transplant.…”

Section: Il28b Polymorphism and Clinical Features Of Chronic Hcv Infementioning

confidence: 99%

IL28B in hepatitis C virus infection: translating pharmacogenomics into clinical practice

2010

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Three landmark genome-wide association studies (GWAS) published in 2009 identified the interleukin (IL) 28B gene locus as pivotal to the pathogenesis of hepatitis C virus (HCV) infection. Polymorphisms near the IL28B gene not only predicted treatment-induced and spontaneous recovery from HCV infection, but they also explained, to some extent, the difference in response rates between Caucasians and African Americans to standard therapy with pegylated interferon and ribavirin. The revelation that IL28B, an innate cytokine, plays an essential role in the pathogenesis, outcomes, and treatment responses to HCV infection has triggered a gold rush and an ever increasing number of reports on the subject are being presented at international conferences and in scientific journals. This review will summarize currently available data on the clinical impact of IL28B polymorphisms on HCV infection and the potential mechanisms for its effects. It will conclude with a discussion on how the research observations may translate into clinical practice and drug development.

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“…Due to the relatively small cohort, we were not able to demonstrate genotype-specific differences in baseline lathosterol levels and virologic response among cirrhotic patients. Other host variables such as IFNL3 gene variants have been associated with higher levels of LDL-C and ApoB for HCV GT1 but not GT3 [54]. However, there was no association between IFNL3 rs12979860 genotype with relapse in our cohort, and was not further evaluated in relation to sterol intermediates.…”

Section: Discussionmentioning

confidence: 64%

Dysregulation of distal cholesterol biosynthesis in association with relapse and advanced disease in CHC genotype 2 and 3 treated with sofosbuvir and ribavirin

Younossi

Stepanova

Estep

et al. 2016

Journal of Hepatology

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Interferon-lambda genotype and low serum low-density lipoprotein cholesterol levels in patients with chronic hepatitis C infection

Cited by 110 publications

References 48 publications

Genetic variation in the interleukin -28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection

Genetic variation in the interleukin -28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection

IL28B in hepatitis C virus infection: translating pharmacogenomics into clinical practice

Dysregulation of distal cholesterol biosynthesis in association with relapse and advanced disease in CHC genotype 2 and 3 treated with sofosbuvir and ribavirin

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