IL28B gene polymorphism is correlated with changes in low-density lipoprotein cholesterol levels after clearance of hepatitis C virus using direct-acting antiviral treatment.
direct-acting antiviral agent
hepatitis C virus
interleukin-28B gene
low-density lipoprotein cholesterol
sustained virologic response
Journal
Journal of gastroenterology and hepatology
ISSN: 1440-1746
Titre abrégé: J Gastroenterol Hepatol
Pays: Australia
ID NLM: 8607909
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
29
03
2019
revised:
08
05
2019
accepted:
23
05
2019
pubmed:
31
5
2019
medline:
4
8
2020
entrez:
31
5
2019
Statut:
ppublish
Résumé
Direct-acting antivirals (DAAs) rapidly clear hepatitis C virus (HCV), but the lipid dynamics after DAA treatment remain unknown. Low-density lipoprotein (LDL) cholesterolemia is the predicting factor for the onset and death of atherosclerotic cardiovascular diseases. Thus, in this study, we examined the frequency and risk of hyper-LDL cholesterolemia in HCV patients who achieved sustained virologic response (SVR) with DAA treatment. A total of 121 patients with HCV genotype 1b, who achieved SVR with DAA treatment, were examined for serum levels of total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein, and triglycerides from the start of treatment until 2 years after SVR (SVR-2y). ΔLDL-C was defined as the change in LDL-C levels from treatment initiation to SVR-2y. Hyper-LDL cholesterolemia was defined as ≥ 140 mg/dL LDL-C at SVR-2y. Stepwise multiple regression analysis was performed to determine whether ΔLDL-C and hyper-LDL cholesterolemia are associated with other factors, including viral kinetics. A total of 63, 3, and 55 patients were administered daclatasvir + asunaprevir, ombitasvir + paritaprevir + ritonavir, and ledipasvir + sofosbuvir, respectively. ΔLDL-C in patients with the IL28B (rs8099917) TG/GG genotype was significantly higher than in those with IL28B TT (27.3 ± 27.0 and 9.6 ± 27.3 mg/dL; P < 0.001). In addition, IL28B TG/GG was an independent risk factor for hyper-LDL cholesterolemia (odds ratio: 8.47; P < 0.001). An IL28B polymorphism is associated with ΔLDL-C and hyper-LDL cholesterolemia after achieving SVR. Thus, lipid markers should be carefully monitored in patients who achieve SVR with DAA.
Sections du résumé
BACKGROUND
BACKGROUND
Direct-acting antivirals (DAAs) rapidly clear hepatitis C virus (HCV), but the lipid dynamics after DAA treatment remain unknown. Low-density lipoprotein (LDL) cholesterolemia is the predicting factor for the onset and death of atherosclerotic cardiovascular diseases. Thus, in this study, we examined the frequency and risk of hyper-LDL cholesterolemia in HCV patients who achieved sustained virologic response (SVR) with DAA treatment.
METHODS
METHODS
A total of 121 patients with HCV genotype 1b, who achieved SVR with DAA treatment, were examined for serum levels of total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein, and triglycerides from the start of treatment until 2 years after SVR (SVR-2y). ΔLDL-C was defined as the change in LDL-C levels from treatment initiation to SVR-2y. Hyper-LDL cholesterolemia was defined as ≥ 140 mg/dL LDL-C at SVR-2y. Stepwise multiple regression analysis was performed to determine whether ΔLDL-C and hyper-LDL cholesterolemia are associated with other factors, including viral kinetics.
RESULTS
RESULTS
A total of 63, 3, and 55 patients were administered daclatasvir + asunaprevir, ombitasvir + paritaprevir + ritonavir, and ledipasvir + sofosbuvir, respectively. ΔLDL-C in patients with the IL28B (rs8099917) TG/GG genotype was significantly higher than in those with IL28B TT (27.3 ± 27.0 and 9.6 ± 27.3 mg/dL; P < 0.001). In addition, IL28B TG/GG was an independent risk factor for hyper-LDL cholesterolemia (odds ratio: 8.47; P < 0.001).
CONCLUSIONS
CONCLUSIONS
An IL28B polymorphism is associated with ΔLDL-C and hyper-LDL cholesterolemia after achieving SVR. Thus, lipid markers should be carefully monitored in patients who achieve SVR with DAA.
Substances chimiques
Antiviral Agents
0
Cholesterol, LDL
0
interferon-lambda, human
0
Interferons
9008-11-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2019-2027Informations de copyright
© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
Références
Moriya K, Yotsuyanagi H, Shintani Y et al. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J. Gen. Virol. 1997; 78: 1527-1531.
Nakamura M, Kanda T, Nakamoto S et al. No correlation between PNPLA3 rs738409 genotype and fatty liver and hepatic cirrhosis in Japanese patients with HCV. PLoS ONE 2013; 8: e81312.
Miyanari Y, Atsuzawa K, Usuda N et al. The lipid droplet is an important organelle for hepatitis C virus production. Nat. Cell Biol. 2007; 9: 1089-1097.
Ko YL, Morihara D, Shibata K et al. Factors attenuating zinc deficiency improvement in direct-acting antiviral agent-treated chronic hepatitis C virus infection. Nutrients 2018; 10.
Fartoux L, Chazouilleres O, Wendum D, Poupon R, Serfaty L. Impact of steatosis on progression of fibrosis in patients with mild hepatitis C. Hepatology 2005; 41: 82-87.
Schaefer EAK, Chung RT. HCV and host lipids: an intimate connection. Semin. Liver Dis. 2013; 33: 358-368.
Popescu CI, Riva L, Vlaicu O, Farhat R, Rouille Y, Dubuisson J. Hepatitis C virus life cycle and lipid metabolism. Biology 2014; 3: 892-921.
Bassendine MF, Sheridan DA, Bridge SH, Felmlee DJ, Neely RD. Lipids and HCV. Semin. Immunopathol. 2013; 35: 87-100.
Aizawa Y, Seki N, Nagano T, Abe H. Chronic hepatitis C virus infection and lipoprotein metabolism. World J. Gastroenterol. 2015; 21: 10299-10313.
Tada S, Saito H, Ebinuma H et al. Treatment of hepatitis C virus with peg-interferon and ribavirin combination therapy significantly affects lipid metabolism. Hepatol Res: Off. J. Jpn Soc. Hepatol. 2009; 39: 195-199.
Corey KE, Kane E, Munroe C, Barlow LL, Zheng H, Chung RT. Hepatitis C virus infection and its clearance alter circulating lipids: implications for long-term follow-up. Hepatology 2009; 50: 1030-1037.
Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97: 1837-1847.
Imamura T, Doi Y, Arima H et al. LDL cholesterol and the development of stroke subtypes and coronary heart disease in a general Japanese population: the Hisayama study. Stroke 2009; 40: 382-388.
Imano H, Noda H, Kitamura A et al. Low-density lipoprotein cholesterol and risk of coronary heart disease among Japanese men and women: the Circulatory Risk in Communities Study (CIRCS). Prev. Med. 2011; 52: 381-386.
Noda H, Iso H, Irie F, Sairenchi T, Ohtaka E, Ohta H. Gender difference of association between LDL cholesterol concentrations and mortality from coronary heart disease amongst Japanese: the Ibaraki Prefectural Health Study. J. Intern. Med. 2010; 267: 576-587.
Yokokawa H, Yasumura S, Tanno K et al. Serum low-density lipoprotein to high-density lipoprotein ratio as a predictor of future acute myocardial infarction among men in a 2.7-year cohort study of a Japanese northern rural population. J. Atheroscler. Thromb. 2011; 18: 89-98.
Noda H, Iso H, Irie F et al. Low-density lipoprotein cholesterol concentrations and death due to intraparenchymal hemorrhage: the Ibaraki Prefectural Health Study. Circulation 2009; 119: 2136-2145.
Teramoto T, Sasaki J, Ishibashi S et al. Executive Summary of the Japan Atherosclerosis Society (JAS) Guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan-2012 version. J. Atheroscler. Thromb. 2013; 20: 517-523.
Chida T, Kawata K, Ohta K et al. Rapid changes in serum lipid profiles during combination therapy with daclatasvir and asunaprevir in patients infected with hepatitis C virus genotype 1b. Gut. Liver. 2018; 12: 201-207.
Endo D, Satoh K, Shimada N, Hokari A, Aizawa Y. Impact of interferon-free antivirus therapy on lipid profiles in patients with chronic hepatitis C genotype 1b. World J. Gastroenterol. 2017; 23: 2355-2364.
Inoue T, Goto T, Iio E et al. Changes in serum lipid profiles caused by three regimens of interferon-free direct-acting antivirals for patients infected with hepatitis C virus. Hepatol. Res.: Off. J. Jpn Soc. Hepatol. 2018; 48: E203-E212.
Chaudhury CS, Sheehan J, Chairez C et al. No improvement in hemoglobin A1c following hepatitis C viral clearance in patients with and without HIV. J. Infect. Dis. 2017; 217: 47-50.
Li Y, Chen Y, Zhao Y. The diagnostic value of the FIB-4 index for staging hepatitis B-related fibrosis: a meta-analysis. PLoS ONE 2014; 9: e105728.
Tanaka Y, Nishida N, Sugiyama M et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat. Genet. 2009; 41: 1105-1109.
Meissner EG, Lee YJ, Osinusi A et al. Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1-infected patients. Hepatology 2015; 61: 790-801.
Hashimoto S, Yatsuhashi H, Abiru S et al. Rapid increase in serum low-density lipoprotein cholesterol concentration during hepatitis C interferon-free treatment. PLoS ONE 2016; 11: e0163644.
Beig J, Orr D, Harrison B, Gane E. Hepatitis C virus eradication with new interferon-free treatment improves metabolic profile in hepatitis C virus-related liver transplant recipients. Liver Transpl: Off Publ. Am. Assoc. Study Liver Dis. Int. Liver Transpl. Soc. 2018; 24: 1031-1039.
Carvalho JR, Velosa J, Serejo F. Lipids, glucose and iron metabolic alterations in chronic hepatitis C after viral eradication-comparison of the new direct-acting antiviral agents with the old regimens. Scand. J. Gastroenterol. 2018; 53: 857-863.
Gitto S, Cicero AFG, Loggi E et al. Worsening of serum lipid profile after direct acting antiviral treatment. Ann. Hepatol. 2018; 17: 64-75.
Morales AL, Junga Z, Singla MB, Sjogren M, Torres D. Hepatitis C eradication with sofosbuvir leads to significant metabolic changes. World J. Hepatol. 2016; 8: 1557-1563.
Adinolfi LE, Nevola R, Guerrera B et al. Hepatitis C virus clearance by direct-acting antiviral treatments and impact on insulin resistance in chronic hepatitis C patients. J. Gastroenterol. Hepatol. 2018; 33: 1379-1382.
Schlevogt B, Deterding K, Port K et al. Interferon-free cure of chronic hepatitis C is associated with weight gain during long-term follow-up. Z. Gastroenterol. 2017; 55: 848-856.
Ge D, Fellay J, Thompson AJ et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461: 399-401.
Suppiah V, Moldovan M, Ahlenstiel G et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat. Genet. 2009; 41: 1100-1104.
Li JH, Lao XQ, Tillmann HL et al. Interferon-lambda genotype and low serum low-density lipoprotein cholesterol levels in patients with chronic hepatitis C infection. Hepatology 2010; 51: 1904-1911.
Tillmann HL, Patel K, Muir AJ et al. Beneficial IL28B genotype associated with lower frequency of hepatic steatosis in patients with chronic hepatitis C. J. Hepatol. 2011; 55: 1195-1200.
Ohnishi M, Tsuge M, Kohno T et al. IL28B polymorphism is associated with fatty change in the liver of chronic hepatitis C patients. J. Gastroenterol. 2012; 47: 834-844.
Honda M, Sakai A, Yamashita T et al. Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterology 2010; 139: 499-509.
Hsu YC, Ho HJ, Huang YT et al. Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection. Gut. 2015; 64: 495-503.
Mahale P, Engels EA, Li R et al. The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection. Gut. 2018; 67: 553-561.