Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Lipid accumulation in the liver triggers inflammation and leads to NAFLD. Prolonged inflammation will worsen the disease progression. Pro-inflammatory cytokines, including interleukin (IL)-12, plays a role in the inflammatory process. This study aimed to determine the association between IL-12 and NAFLD severity.
Methods: A cross-sectional study was conducted between January and July 2019 in Haji Adam Malik Hospital Medan, Indonesia. Subjects were patients aged 18 years or older diagnosed with NAFLD based on ultrasound. Exclusion criteria were excessive alcohol consumption, other primary liver diseases, malignancies, and cardio-metabolic disturbances. Serum IL-12 level was determined using an enzyme-linked immunosorbent assay method. The severity of NAFLD was assessed using the BARD score and NAFLD fibrosis score.
Results: A total of 100 subjects were enrolled with male predominant. The mean age of subjects was 54.97 ± 8.85 years, and the most frequent comorbidity was obesity. Most subjects had mild to moderate disease progression. Serum IL-12 level was higher in more severe NAFLD based on ultrasound grading (P < 0.001), BARD score (P = 0.003), and NAFLD fibrosis score (P = 0.005). A positive correlation was observed between serum IL-12 level and BARD score (P < 0.001) with sufficient accuracy (AUC = 0.691, P = 0.014).
Conclusion: Serum IL-12 level was associated with the severity of NAFLD. Higher serum IL-12 level was observed in more severe NAFLD progression.
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1. LI S., HONG M., TAN H., WANG N., FENG Y. Insights into the role and interdependence of oxidative stress in inflammation in liver diseases. Oxid Med Cell Longev. 2016; 2016:4234061.
2. ZHAN Y., AN W. Roles of liver innate immune cells in nonalcoholic fatty liver disease. World J Gastroenterol. 2010; 16(37):4652-4660.
3. LIU Y., ZHONG G., TAN H., HAO F., HU J. Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta analysis. Sci Rep. 2019; 9:11124.
4. KUMAR A., SINGH AK., PANDA PK., NISCHAL N., SONEJA M. Non-alcoholic fatty liver disease diagnosis, grading and staging; a simplified tool for clinicians. JAM. 2017; 6(1):15-22.
5. LUCI C, VIEIRA E, PERCHET T, GUAL P, GOLUB R. Natural killer cells and type 1 innate lymphoid cells are new actors in non-alcoholic fatty liver disease. Front Immunol. 2019;10:1192.
6. HAMMERICH L, TACKE F. Interleukins in chronic liver disease: lessons learned from experimental mouse models. Clin Exp Gastroenterol. 2014;7:297–306.
7. HAMMERICH L., TACKE F. Interleukins in chronic liver disease: lessons learned from experimental mouse models. Clin Exp Gastroenterol. 2014; 7:297-306.
8. ARRESE M., CABRERA D., KALERGIS AM., FELDSTEIN AE. Innate immunity and inflammation in NAFLD/NASH. Dig Dis Sci. 2016; 61(5):1294-1303.
9. GILES DA., MORENO-FERNANDEZ ME., DIVANOVIC S. IL-17 axis driven inflammation in non-alcoholic fatty liver disease progression. Curr Drug Targets. 2015; 16(12):1315-1323.
10. DASARATHY S., DASARATHY S., KHIYAMI A., JOSEPH R., LOPEZ R., MCCULLOUGH AJ. Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study. J Hepatol. 2009; 51(6):1061–1067.
11. SHANNON A., ALKHOURI N., CARTER-KENT C., MONTI L., DEVITO R., LOPEZ R., et al. Ultrasonographic quantitative estimation of hepatic steatosis in children with NAFLD. J Pediatr Gastroenterol Nutr. 2011; 53(2):190–195.
12. YOUNOSSI ZM., KOENIG AB., ABDELATIF D., FAZEL Y., HENRY L., WYMER M. Global epidemiology of nonalcoholic fatty liver disease – meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64(1):73-84.
13. DYSON JK., ANSTEE QM., MCPHERSON S. Non-alcoholic fatty liver disease: a practical approach to diagnosis and staging. Frontline Gastroenterol. 2014; 5(3):211-218.
14. JENNISON E., PATEL J., SCORLETTI E., BYRNE CD. Diagnosis and management of non-alcoholic fatty liver disease. Postgrad Med J. 2019; 95(1124):314-322.
15. SANNA C, ROSSO C, MARIETTI M, BUGIANESI E. Non-alcoholic fatty liver disease and extra-hepatic cancers. Int J Mol Sci. 2016; 17(5):717.
16. STOJSAVLJEVIC S., PALCIC MG., JUKIC LV., DUVNJAK LS, DUVNJAK M. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014; 20(48):18070-18091.
17. SUTTI S., ALBANO E. Adaptive immunity: an emerging player in the progression of NAFLD. Nat Rev Gastroenterol Hepatol. 2020; 17(2):81-92.
18. BRAUNERSREUTHER V., VIVIANI GL., MACH F., MONTECUCCO F. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World J Gastroenterol. 2012; 18(8):727-735.
19. KREMER M., THOMAS E., MILTON RJ., PERRY AW., VAN ROOIJEN N., WHEELER MD. Kupffer cell and interleukin-12 dependent loss of natural killer T cells in hepatosteatosis. Hepatology. 2010; 51(1):130-141.
20. AJMERA V., PERITO ER., BASS NM., TERRAULT NA., YATES KP., GILL R., et al. Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease. Hepatology. 2017; 65(1):65-77.
21. TARANTINO G., CITRO V, CONFORTI P, BALSANO C, CAPONE D. Is there a link between basal metabolic rate, spleen volume and hepatic growth factor levels in patients with obesity-related NAFLD? JCM. 2019;8:1510.
22. XIAO G, ZHU S, XIAO X, YAN L, YANG J, WU G. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Hepatol. 2017;66:1486–501.
23. CLEVELAND E, BANDY A, VANWAGNER LB. Diagnostic challenges of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Clin Liver Dis (Hoboken). 2018/04/20 ed. 2018;11:98–104.