Diagnostic capabilities of kallistatin, IL-10 and IL-1β in patients with non-alcoholic fatty liver disease and hypertension
Yıl 2021,
Cilt: 13 Sayı: 2, 61 - 69, 31.08.2021
Anastasiia Rozhdestvenska
,
Natalia Zhelezniakova
Öz
Introduction. Non-alcoholic fatty liver disease (NAFLD) is closely linked to hypertension (HT) and affects about 25% of the adult population. An important issue remains the search for non-invasive biomarkers for NAFLD diagnosis.
The objective of the study was to evaluate the diagnostic value of kallistatin, interleukin-10 (IL-10) and interleukin-1β (IL-1β) in diagnosis of NAFLD in combination with HT.
Materials and methods. 115 patients with NAFLD at the stage of non-alcoholic steatohepatitis (NASH) were examined, including 63 patients with comorbidity of NASH and HT (main group) and 52 people with isolated NASH (comparison group). Clinical and laboratory parameters were evaluated; plasma kallistatin, IL-10 and IL-1β levels were measured in all patients.
Results. Kallistatin levels averaged 65.03 ng/ml, 83.42 ng/ml and 111.70 ng/ml in patients with NAFLD and HT, isolated NAFLD and control group, respectively. The IL-10 level was 2.69 ng/ml and 4.90 ng/ml in patients with comorbid and isolated NAFLD, respectively, while control results averaged 8.17 ng/ml. The IL-1β level in NAFLD and HT group was 4.76 pg/ml, and in isolated NAFLD group the indicator averaged 4.02 pg/ml, which exceeded the control values (0.59 pg/ml).
Conclusions. The course of both isolated NAFLD and comorbidity NAFLD with HT was accompanied by significant changes of kallistatin, IL-10 and IL-1β levels. Higher HT stage and BP grade, increased BMI and high CRP levels are associated with significantly more pronounced deviations of these indicators in patients with NAFLD and HT. The obtained data provide the possibility to consider the kallistatin, IL-10 and IL-1β as biomarkers of NAFLD severity.
Teşekkür
We express our gratitude to the Prof. Dr. Barış ÇAKIR (Maltepe University, Department of Physiology, TURKEY), who offered to publish the article in the “Maltepe Medical Journal” after our presentation in the MEDNS-21 congress.
Kaynakça
- Mitra S, De A, Chowdhury A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Translational Gastroenterology and Hepatology. 2020;5:16. doi:10.21037/tgh.2019.09.08
- Marieke V, Jan W, Karin K, et al. Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Patients With Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. The Journal of Clinical Endocrinology & Metabolism. 2020;105(12);3842–3853. doi:10.1210/clinem/dgaa575
- Wu S, Wu F, Ding Y, et al. Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis. Scientific Reports. 2016;6:33386. doi: 10.1038/srep33386.
- Zhao YC, Zhao GJ, Chen Z, et al. Nonalcoholic Fatty Liver Disease: An Emerging Driver of Hypertension. Hypertension. 2020;75(2):275-284. doi: 10.1161/hypertensionaha.119.13419
- Oikonomou D, Georgiopoulos G, Katsi V, et al. Non-alcoholic fatty liver disease and hypertension: coprevalent or correlated? European Journal of Gastroenterology & Hepatology. 2018;30(9):979-985. doi: 10.1097/MEG.0000000000001191.
- Targher G, Byrne CD, Lonardo A, et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. Journal of Hepatology. 2016;65(3):589-600. doi: 10.1016/j.jhep.2016.05.013.
- Halla MR, Fawzy AA, Nabila AEM, et al. Evaluation of kallistatin as a biomarker in chronic hepatitis C patients. World journal of pharmacy and pharmaceutical sciences. 2017;6(9):150-174. doi: 10.20959/WJPPS20179-10058
- Ma C, Yin H, Zhong J, et al. Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation. International Journal of Oncology. 2017;50(6);2000–2010. doi:10.3892/ijo.2017.3972
- Fathia A. Mannaa, Khaled G. Abdel-Wahhab. Physiological potential of cytokines and liver damages. Hepatoma Res 2016; 2: 131-143
- Tilg H, Effenberger M, Adolph TE. A role for IL-1 inhibitors in the treatment of non-alcoholic fatty liver disease (NAFLD)? Expert Opin Investig Drugs. 2020 Feb;29(2):103-106. doi: 10.1080/13543784.2020.1681397.
- 11. Nelson JE, Handa P, Aouizerat B, Wilson L, Vemulakonda LA, Yeh MM, Kowdley KV; NASH Clinical Research Network. Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Aliment Pharmacol Ther. 2016 Dec;44(11-12):1253-1264. doi: 10.1111/apt.13824.
- Fathia A. Mannaa, Khaled G. Abdel-Wahhab. Physiological potential of cytokines and liver damages. Hepatoma Res. 2016; 2: 131-143
- Steen, E. H., Wang, X., Balaji, S., Butte, M. J., Bollyky, P. L., & Keswani, S. G. The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis. Advances in Wound Care. 2019. doi:10.1089/wound.2019.1032
- Braunersreuther V, Viviani GL, Mach F, Montecucco F. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World journal of gastroenterology. 2012; 18(8):727–735. https://doi.org/10.3748/wjg.v18.i8.727
- Krishnan SM, Sobey CG, Latz E, Mansell A, Drummond GR. IL-1β and IL-18: inflammatory markers or mediators of hypertension?. Br J Pharmacol. 2014;171(24):5589-5602. doi:10.1111/bph.12876
- Lima VV, Zemse SM, Chiao CW, Bomfim GF, Tostes RC, Clinton Webb R, Giachini FR. Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice. Life Sci. 2016 Jan 15;145:137-43. doi: 10.1016/j.lfs.2015.12.009.
- Gateva A, Assyov Y, Velikova T, et al. Increased kallistatin levels in patients with obesity and prediabetes compared to normal glucose tolerance. Endocrine Research. 2017;42(2):163-168. doi:10.1080/07435800.2017.1286671
- Ma L, Wu J, Zheng Y, et al. Heparin Blocks the Inhibition of Tissue Kallikrein 1 by Kallistatin through Electrostatic Repulsion. Biomolecules. 2020;10(6):828. doi:10.3390/biom10060828
- Wu H, Li R, Zhang Z, et al. Kallistatin inhibits tumour progression and platinum resistance in high-grade serous ovarian cancer. Journal of Ovarian Research. 2019;12(1):125. doi:10.1186/s13048-019-0601-6
- Al-Shimaa MA, Moustafa SA, Noha MS, et al. Evaluation of clinical significance of kallistatin and macrophage inflammatory protein-1b for the diagnosis of liver cirrhosis and hepatocellular carcinoma in Egyptian patients. Research Journal of Pharmacy and Technology. 2019;12(1):43-49. doi: 10.5958/0974-360X.2019.00009.X
- 21. Prystupa A, Kiciński P, Luchowska-Kocot D, et al. Factors influencing serum chemerin and kallistatin concentrations in patients with alcohol-induced liver cirrhosis. Annals of Agricultural and Environmental Medicine. 2019;26(1):143-147. doi:10.26444/aaem/100536
- Bocsan IC, Milaciu MV, Pop RM, Vesa SC, Ciumarnean L, Matei DM, Buzoianu AD. Cytokines Genotype-Phenotype Correlation in Nonalcoholic Steatohepatitis. Oxidative Medicine and Cellular Longevity. 2017;1–7. doi:10.1155/2017/4297206
- Ampuero J, Aller R, Gallego-Durán R, Crespo J, Calleja, JL, García-Monzón C, Romero GM. Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH. Journal of Hepatology. 2020; 73(1):17-25. doi: 10.1016/j.jhep.2020.02.028.
- Liu P, Tang Y, Guo X, Zhu X, He M, Yuan J, Yao P. Bidirectional association between nonalcoholic fatty liver disease and hypertension from the Dongfeng-Tongji cohort study. Journal of the American Society of Hypertension. 2018. doi:10.1016/j.jash.2018.06.013
- Ma J, Hwang SJ, Pedley A, Massaro JM, Hoffmann U, Chung RT, Long MT. Bi-directional analysis between fatty liver and cardiovascular disease risk factors. Journal of Hepatology. 2017;66(2):390–397. doi:10.1016/j.jhep.2016.09.022
- Aneni EC, Oni ET, Martin SS, Blaha MJ, Agatston AS, Feldman T, Nasir K. Blood pressure is associated with the presence and severity of nonalcoholic fatty liver disease across the spectrum of cardiometabolic risk. Journal of Hypertension. 2015;33(6):1207- 1214. doi: 10.1097/HJH.0000000000000532.
- Ilan Y. Analogy between non-alcoholic steatohepatitis (NASH) and hypertension: a stepwise patient-tailored approach for NASH treatment. Annals of gastroenterology. 2018;31(3):296–304.
- Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2015;47: 181- 190.
- Cheng Z, Lv Y, Pang S, et al. Kallistatin, a new and reliable biomarker for the diagnosis of liver cirrhosis. Acta Pharmaceutica Sinica B. 2015;5(3):194-200. doi:10.1016/j.apsb.2015.02.003.
- Frühbeck G, Gómez-Ambrosi J, Rodríguez A, et al. Novel protective role of kallistatin in obesity by limiting adipose tissue low grade inflammation and oxidative stress. Metabolism. 2018;87:123-135. doi:10.1016/j.metabol.2018.04.004
- Chao J, Guo Y, Chao L. Protective Role of Endogenous Kallistatin in Vascular Injury and Senescence by Inhibiting Oxidative Stress and Inflammation. Oxidative Medicine and Cellular Longevity. 2018;2018:4138560. doi:10.1155/2018/4138560
- Nelson JE, Handa P, Aouizerat B, Wilson L, Vemulakonda LA, Yeh MM, Kowdley KV; NASH Clinical Research Network. Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Aliment Pharmacol Ther. 2016 Dec;44(11-12):1253-1264. doi: 10.1111/apt.13824.
- Saraiva M, Vieira P, O’Garra A. Biology and therapeutic potential of interleukin-10. The Journal of Experimental Medicine. 2019;jem.20190418. doi:10.1084/jem.20190418
Alkole bağlı olmayan yağlı karaciğer hastalığı ve hipertansiyonu olan hastalarda kallistatin, IL-10 ve IL1β'nin tanısal güçleri
Yıl 2021,
Cilt: 13 Sayı: 2, 61 - 69, 31.08.2021
Anastasiia Rozhdestvenska
,
Natalia Zhelezniakova
Öz
Giriş. Alkolsüz yağlı karaciğer hastalığı, hipertansiyonla yakından bağlantılıdır ve yetişkin nüfusun yaklaşık% 25'ini etkiler. Alkolsüz yağlı karaciğer hastalığı teşhisi için invazif olmayan biyobelirteçlerin araştırılması önemli bir konu olmaya devam etmektedir.
Çalışmanın amacı, hipertansiyon ile kombinasyon halinde alkolsüz yağlı karaciğer hastalığı tanısında kallistatin, interlökin-10 (IL-10) ve interlökin-1β (IL-1β) 'nin tanısal değerini değerlendirmektir.
Malzemeler ve yöntemler. Alkolsüz steatohepatit evresinde alkolsüz yağlı karaciğer hastalığı olan 115 hasta incelendi; bunlara eşlik eden alkolsüz steatohepatit ve hipertansiyonu olan 63 hasta (ana grup) ve izole alkolsüz steatohepatitli 52 kişi (karşılaştırma grubu). Klinik ve laboratuvar parametreleri değerlendirildi; Tüm hastalarda plazma kallistatin, IL-10 ve IL-1β seviyeleri ölçüldü.
Sonuçlar. Alkolsüz yağlı karaciğer hastalığı ve hipertansiyonu olan hastalarda, izole alkolsüz yağlı karaciğer hastalığı ve kontrol grubunda ortalama kallistatin seviyeleri sırasıyla 65.03 ng / ml, 83.42 ng / ml ve 111.70 ng / ml olmuştur. IL-10 seviyesi, komorbid ve izole alkolsüz yağlı karaciğer hastalığı olan hastalarda sırasıyla 2.69 ng / ml ve 4.90 ng / ml iken, kontrol sonuçlarının ortalaması 8.17 ng / ml idi. Alkolsüz yağlı karaciğer hastalığı ve HT grubunda IL-1β seviyesi 4.76 pg / ml idi ve izole alkolsüz yağlı karaciğer hastalığı grubunda gösterge ortalama 4.02 pg / ml idi ve bu da kontrol değerlerini (0.59 pg / ml) aştı. .
Sonuçlar. Hem izole alkolik olmayan yağlı karaciğer hastalığı hem de alkolsüz yağlı karaciğer hastalığı ile birlikte hipertansiyonun seyrine kallistatin, IL-10 ve IL-1p seviyelerinde önemli değişiklikler eşlik etti. Alkolsüz yağlı karaciğer hastalığı ve hipertansiyonu olan hastalarda daha yüksek hipertansiyon evresi ve kan basıncı derecesi, artan vücut kitle indeksi ve yüksek C-reaktif protein seviyeleri, bu göstergelerin önemli ölçüde daha belirgin sapmalarıyla ilişkilidir. Elde edilen veriler, kallistatin, IL-10 ve IL-1β'nın alkolik olmayan yağlı karaciğer hastalığı ciddiyetinin biyolojik belirteçleri olarak dikkate alınmasını sağlar.
Kaynakça
- Mitra S, De A, Chowdhury A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Translational Gastroenterology and Hepatology. 2020;5:16. doi:10.21037/tgh.2019.09.08
- Marieke V, Jan W, Karin K, et al. Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Patients With Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. The Journal of Clinical Endocrinology & Metabolism. 2020;105(12);3842–3853. doi:10.1210/clinem/dgaa575
- Wu S, Wu F, Ding Y, et al. Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis. Scientific Reports. 2016;6:33386. doi: 10.1038/srep33386.
- Zhao YC, Zhao GJ, Chen Z, et al. Nonalcoholic Fatty Liver Disease: An Emerging Driver of Hypertension. Hypertension. 2020;75(2):275-284. doi: 10.1161/hypertensionaha.119.13419
- Oikonomou D, Georgiopoulos G, Katsi V, et al. Non-alcoholic fatty liver disease and hypertension: coprevalent or correlated? European Journal of Gastroenterology & Hepatology. 2018;30(9):979-985. doi: 10.1097/MEG.0000000000001191.
- Targher G, Byrne CD, Lonardo A, et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. Journal of Hepatology. 2016;65(3):589-600. doi: 10.1016/j.jhep.2016.05.013.
- Halla MR, Fawzy AA, Nabila AEM, et al. Evaluation of kallistatin as a biomarker in chronic hepatitis C patients. World journal of pharmacy and pharmaceutical sciences. 2017;6(9):150-174. doi: 10.20959/WJPPS20179-10058
- Ma C, Yin H, Zhong J, et al. Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation. International Journal of Oncology. 2017;50(6);2000–2010. doi:10.3892/ijo.2017.3972
- Fathia A. Mannaa, Khaled G. Abdel-Wahhab. Physiological potential of cytokines and liver damages. Hepatoma Res 2016; 2: 131-143
- Tilg H, Effenberger M, Adolph TE. A role for IL-1 inhibitors in the treatment of non-alcoholic fatty liver disease (NAFLD)? Expert Opin Investig Drugs. 2020 Feb;29(2):103-106. doi: 10.1080/13543784.2020.1681397.
- 11. Nelson JE, Handa P, Aouizerat B, Wilson L, Vemulakonda LA, Yeh MM, Kowdley KV; NASH Clinical Research Network. Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Aliment Pharmacol Ther. 2016 Dec;44(11-12):1253-1264. doi: 10.1111/apt.13824.
- Fathia A. Mannaa, Khaled G. Abdel-Wahhab. Physiological potential of cytokines and liver damages. Hepatoma Res. 2016; 2: 131-143
- Steen, E. H., Wang, X., Balaji, S., Butte, M. J., Bollyky, P. L., & Keswani, S. G. The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis. Advances in Wound Care. 2019. doi:10.1089/wound.2019.1032
- Braunersreuther V, Viviani GL, Mach F, Montecucco F. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World journal of gastroenterology. 2012; 18(8):727–735. https://doi.org/10.3748/wjg.v18.i8.727
- Krishnan SM, Sobey CG, Latz E, Mansell A, Drummond GR. IL-1β and IL-18: inflammatory markers or mediators of hypertension?. Br J Pharmacol. 2014;171(24):5589-5602. doi:10.1111/bph.12876
- Lima VV, Zemse SM, Chiao CW, Bomfim GF, Tostes RC, Clinton Webb R, Giachini FR. Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice. Life Sci. 2016 Jan 15;145:137-43. doi: 10.1016/j.lfs.2015.12.009.
- Gateva A, Assyov Y, Velikova T, et al. Increased kallistatin levels in patients with obesity and prediabetes compared to normal glucose tolerance. Endocrine Research. 2017;42(2):163-168. doi:10.1080/07435800.2017.1286671
- Ma L, Wu J, Zheng Y, et al. Heparin Blocks the Inhibition of Tissue Kallikrein 1 by Kallistatin through Electrostatic Repulsion. Biomolecules. 2020;10(6):828. doi:10.3390/biom10060828
- Wu H, Li R, Zhang Z, et al. Kallistatin inhibits tumour progression and platinum resistance in high-grade serous ovarian cancer. Journal of Ovarian Research. 2019;12(1):125. doi:10.1186/s13048-019-0601-6
- Al-Shimaa MA, Moustafa SA, Noha MS, et al. Evaluation of clinical significance of kallistatin and macrophage inflammatory protein-1b for the diagnosis of liver cirrhosis and hepatocellular carcinoma in Egyptian patients. Research Journal of Pharmacy and Technology. 2019;12(1):43-49. doi: 10.5958/0974-360X.2019.00009.X
- 21. Prystupa A, Kiciński P, Luchowska-Kocot D, et al. Factors influencing serum chemerin and kallistatin concentrations in patients with alcohol-induced liver cirrhosis. Annals of Agricultural and Environmental Medicine. 2019;26(1):143-147. doi:10.26444/aaem/100536
- Bocsan IC, Milaciu MV, Pop RM, Vesa SC, Ciumarnean L, Matei DM, Buzoianu AD. Cytokines Genotype-Phenotype Correlation in Nonalcoholic Steatohepatitis. Oxidative Medicine and Cellular Longevity. 2017;1–7. doi:10.1155/2017/4297206
- Ampuero J, Aller R, Gallego-Durán R, Crespo J, Calleja, JL, García-Monzón C, Romero GM. Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH. Journal of Hepatology. 2020; 73(1):17-25. doi: 10.1016/j.jhep.2020.02.028.
- Liu P, Tang Y, Guo X, Zhu X, He M, Yuan J, Yao P. Bidirectional association between nonalcoholic fatty liver disease and hypertension from the Dongfeng-Tongji cohort study. Journal of the American Society of Hypertension. 2018. doi:10.1016/j.jash.2018.06.013
- Ma J, Hwang SJ, Pedley A, Massaro JM, Hoffmann U, Chung RT, Long MT. Bi-directional analysis between fatty liver and cardiovascular disease risk factors. Journal of Hepatology. 2017;66(2):390–397. doi:10.1016/j.jhep.2016.09.022
- Aneni EC, Oni ET, Martin SS, Blaha MJ, Agatston AS, Feldman T, Nasir K. Blood pressure is associated with the presence and severity of nonalcoholic fatty liver disease across the spectrum of cardiometabolic risk. Journal of Hypertension. 2015;33(6):1207- 1214. doi: 10.1097/HJH.0000000000000532.
- Ilan Y. Analogy between non-alcoholic steatohepatitis (NASH) and hypertension: a stepwise patient-tailored approach for NASH treatment. Annals of gastroenterology. 2018;31(3):296–304.
- Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2015;47: 181- 190.
- Cheng Z, Lv Y, Pang S, et al. Kallistatin, a new and reliable biomarker for the diagnosis of liver cirrhosis. Acta Pharmaceutica Sinica B. 2015;5(3):194-200. doi:10.1016/j.apsb.2015.02.003.
- Frühbeck G, Gómez-Ambrosi J, Rodríguez A, et al. Novel protective role of kallistatin in obesity by limiting adipose tissue low grade inflammation and oxidative stress. Metabolism. 2018;87:123-135. doi:10.1016/j.metabol.2018.04.004
- Chao J, Guo Y, Chao L. Protective Role of Endogenous Kallistatin in Vascular Injury and Senescence by Inhibiting Oxidative Stress and Inflammation. Oxidative Medicine and Cellular Longevity. 2018;2018:4138560. doi:10.1155/2018/4138560
- Nelson JE, Handa P, Aouizerat B, Wilson L, Vemulakonda LA, Yeh MM, Kowdley KV; NASH Clinical Research Network. Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Aliment Pharmacol Ther. 2016 Dec;44(11-12):1253-1264. doi: 10.1111/apt.13824.
- Saraiva M, Vieira P, O’Garra A. Biology and therapeutic potential of interleukin-10. The Journal of Experimental Medicine. 2019;jem.20190418. doi:10.1084/jem.20190418