Interleukin 28B polymorphisms are the only common genetic variants associated with low‐density lipoprotein cholesterol (LDL‐C) in genotype‐1 chronic hepatitis C and determine the association between LDL‐C and treatment response

Clark, Paul J.; Thompson, Alexander; Zhu, Mingyuan; Vock, David M.; Zhu, Qianqian; Ge, Dongliang; Patel, Keyur; Harrison, Stephen A.; Urban, Thomas; Naggie, Susanna; Fellay, Jacques; Tillmann, Hans L.; Shianna, Kevin V.; Noviello, Stephanie; Pedicone, Lisa D.; Esteban, Rafael; Kwo, P.; Sulkowski, Mark S.; Afdhal, Nezam H.; Albrecht, Janice K.; Goldstein, David B.; McHutchison, John G.; Muir, Andrew J.

doi:10.1111/j.1365-2893.2011.01553.x

Cited by 36 publications

(29 citation statements)

References 34 publications

(56 reference statements)

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“…IL28B polymorphisms influence SVR rates in HCV genotypes 1 and 4 , although its effect in genotypes 2 and 3, which generally respond more favourably to therapy, is less obvious . IL28B genotypes also have associations with hepatic steatosis , post‐transplant re‐infection rates , and serum cholesterol levels . Other noteworthy SNPs identified by GWAS related to HCV therapeutics are the inosine triphosphatase (ITPA) gene polymorphisms on chromosome 20, which protect against ribavirin‐related hemolytic anaemia .…”

Section: Introductionmentioning

confidence: 99%

Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection

Seto

Tsang²,

Liu

et al. 2013

Journal of Viral Hepatitis

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IL28B and inosine triphosphatase (ITPA) polymorphisms are able to predict treatment response and degree of ribavirin-related anaemia, respectively, in the treatment of chronic hepatitis C virus (HCV) infection. However, their roles in the treatment of chronic HCV genotype 6 remain undetermined. Sixty patients who were infected with HCV genotype 6 were commenced on 48 weeks of combination pegylated interferon and ribavirin therapy. Response to therapy, profiles of haemoglobin changes and platelet counts during therapy and their associations with IL28B rs8099917 and ITPA rs1127354 polymorphisms were analysed. The overall sustained virologic response (SVR) rate was 91.7%. 18 patients (30.0%) required a reduction in ribavirin dosage. The distribution of IL28B rs8099917 TT/TG genotypes and ITPA rs1127354 CC/CA genotypes were in Hardy-Weinberg equilibrium. IL28B rs8099917 TT genotype, when compared to TG genotype, was significantly associated with an increased SVR rate (96.2% and 62.5%, respectively) and was the only clinical parameter that predicted SVR (P = 0.014). The same significant association was observed when analysing allelic frequencies (T vs G, P = 0.001). ITPA rs1127354 CA genotype, when compared to CC genotype, was associated with lesser degree of anaemia throughout therapy (P < 0.05 for all time points). ITPA polymorphisms showed no association with changes in platelet count throughout therapy (P > 0.05 for all time points) and was not associated with SVR (P = 0.640). In chronic HCV genotype 6 infection, IL28B polymorphisms were associated with response to therapy. ITPA polymorphisms influenced the degree of anaemia but not thrombocytopenia during therapy.

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Section: Introductionmentioning

confidence: 99%

Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection

Seto

Tsang²,

Liu

et al. 2013

Journal of Viral Hepatitis

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“…Amino acid 70 substitution in the core region and LDL-cholesterol level have already been shown to be predictive factors of SVR to PEG-IFN plus ribavirin therapy 17. In addition, it has been reported that a high serum level of LDL-cholesterol is linked to the IL-28B major allele 18,19. Regarding AFP, it has been reported that AFP level is an independent factor for response to triple therapy of telaprevir, PEG-IFN, and ribavirin in previous nonresponders to PEG-IFN plus ribavirin therapy 20.…”

Section: Discussionmentioning

confidence: 99%

Prediction of a Null Response to Pegylated Interferon α-2b Plus Ribavirin in Patients with High Viral Load Genotype 1b Hepatitis C

Wada¹,

Tamai²,

Kawashima³

et al. 2014

Gut Liver

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Background/AimsThe present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon α-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C.MethodsThe participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured.ResultsSignificant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, α-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks.ConclusionsVirological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response.

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“…In a study on HCV G1, distortion of lipoprotein metabolism was more profound in patients who were non-favorable responders, and decreases of LDL-C, HDL-C, and TG were reported using conventional measurement technologies (26). However, after the discovery of rs8099917 and rs12979860 near the human IL28B gene as a strong host factor affecting the response to peg-IFN plus RBV therapy (27, 28), the significance of lipid profiles on predicting SVR was thought to be doubtful because the power of the IL28B genotype for predicting the efficacy of peg-IFN plus RBV therapy was so strong (29, 30). In the present study, we found that the C/T ratio in fasting serum VLDL was independently associated with SVR along with the IL28B genotype in patients with chronic HCV G1b who were treated with peg-IFNα-2b plus RBV.…”

Section: Discussionmentioning

confidence: 99%

Serum Lipoprotein Profiles and Response to Pegylated Interferon Plus Ribavirin Combination Therapy in Patients With Chronic HCV Genotype 1b Infection

et al. 2013

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BackgroundAbnormal serum lipid profiles have been noted in patients with chronic hepatitis C virus (HCV) infection. Moreover, many reports suggest that serum lipoprotein profiles are more profoundly distorted in patients with HCV G1b infection who have an unfavorable response to pegylated interferon (peg-IFN) plus ribavirin (RBV) combination therapy. However, after the discovery of single nucleotide polymorphisms near the IL28B gene (rs8099917 and rs12979860) as potent predictive factors affecting the response to peg-IFN plus RBV, lipid factors are thought to be confounding factors.ObjectivesTo re-examine the significance of lipoprotein profiles on virological response to peg-IFN plus RBV combination therapy in patients with chronic HCV G1b infection, we examined cholesterol and triglyceride concentrations in each lipoprotein fraction separated by high performance liquid chromatography.Patients and MethodsLipoprotein profiles were examined using fasting sera from 108 patients infected with HCV G1b who had chronic hepatitis, as determined by liver biopsy. Results of lipoprotein profiles and clinical data, including IL28B genotype and amino acid substitution at aa70 of HCV G1b, were compared between patients with a sustained virological response (SVR) and non-SVR or a non-virological response (NVR) and virological responses other than NVR (non-NVR). In addition, significant predictive factors independently associated with virological response to peg-IFNα-2b plus RBV were determined by logistic regression analysis.ResultsAn increased ratio of cholesterol/triglyceride in very low-density lipoprotein (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.01-9.44) along with a major genotype of rs8099917 (OR 9.09; 95% CI 2.94-33.33), were independent predictive factors for SVR. In contrast, lipid factors were not elucidated as independent predictive factors for NVR.ConclusionsExamination of the fasting lipid profile has clinical importance in predicting the efficacy of peg-IFN-α-2b plus RBV combination therapy for patients with HCV G1b even after the discovery of the IL28 genotype as a potent predictive factor.

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Interleukin 28B polymorphisms are the only common genetic variants associated with low‐density lipoprotein cholesterol (LDL‐C) in genotype‐1 chronic hepatitis C and determine the association between LDL‐C and treatment response

Cited by 36 publications

References 34 publications

Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection

Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection

Prediction of a Null Response to Pegylated Interferon α-2b Plus Ribavirin in Patients with High Viral Load Genotype 1b Hepatitis C

Serum Lipoprotein Profiles and Response to Pegylated Interferon Plus Ribavirin Combination Therapy in Patients With Chronic HCV Genotype 1b Infection

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