The effect of obesity and hyperuricemia on liver steatosis and fibrosis in metabolic dysfunction-associated fatty liver disease

Abstract

Abstract: Objective To investigate the influence of obesity and hyperuricemia on steatosis and fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD). Methods A total of MAFLD 510 patients treated at the Department of Hepatology of the Traditional Chinese Medical Hospital Affiliated to Xinjiang Medical University between January 2020 and December 2022 were included in this study. After application of strict the inclusion and exclusion criteria, 402 patients were ultimately selected for analysis. Patients were divided into four groups based on their body mass index (BMI) and hyperuricemia status: non-obese without hyperuricemia group, non-obese hyperuricemia group, obese without hyperuricemia group and obese hyperuricemia group. Clinical parameters were compared across these groups, and liver steatosis and fibrosis were assessed using transient elastography Fibrotouch. Binary Logistic regression was utilized to evaluate the potential interaction between obesity and hyperuricemia in relation to hepatic steatosis and fibrosis. Results Of the 402 patients included in the study, distribution was as follows; 186 patients in the non-obese without hyperuricemia group, 34 patients in the non-obese with hyperuricemia group, 151 patients in the obese without hyperuricemia group, and 31 patients in the obese with hyperuricemia group. Statistically differences were observed in various demographic and clinical parameters among the groups, including age, sex, BMI, ALT, GGT, TG, Cr, UA, Alb, ALT/AST, D-D, FIB-4, BARD, LSM, CAP, drinking and smoking history (P<0.05). Evalution of liver steatosis and liver fibrosis stage based on the fat attenuation parameters and liver stiffness values revealed statistically significant differences among the groups (P<0.05). The proportion of moderate and severe steatosis (81.5%,83.9%, respectively) and progressive hepatic fibrosis (76.8%,87.1%, respectively) was significantly higher in the obese group compared to the non-obese groups. Binary Logistic regression analysis indicated that obesity was a risk factor for moderate-severe steatosis and progressive fibrosis in MAFLD patients. Moreover, the interaction between obesity and hyperuricemia demonstrated a multiplicative effect on the the likelihood of moderate-severe steatosis and progressive fibrosis (Obesity * hyperuricemia interaction term OR>1). Conclusion The findings of this study suggest a synergistic relationship between obesity and hyperuricemia in driving liver steatosis and fibrosis progression in MAFLD patients.

Key words: Obesity, Hyperuricemia, Metabolic dysfunction-associated fatty liver disease, Steatosis, Fibrosis

LIU Yun-xiao, WANG Zhuan-guo, XU Qiang, DOU Jing, WANG Xiao-bo, GUO Yan, GUO Feng, WANG Xiao-zhong. The effect of obesity and hyperuricemia on liver steatosis and fibrosis in metabolic dysfunction-associated fatty liver disease[J]. Chinese Hepatolgy, 2024, 29(3): 303-307.

References

[1] Wang XH, Lin J N, Liu GZ, et al.Women are at a higher risk of chronic metabolic diseases compared to men with increasing body mass index in China[J].Front Endocrinol (Lausanne), 2020, 11:127.
[2] Nan Y, An J, Bao J, et al. The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease[J]. J Hepatol, 2021, 75(2): 454-461.
[3] Van Kleef LA, Ayada I, Alferink LJM, et al. Metabolic dysfunction-associated fatty liver disease improves detection of high liver stiffness: The Rotterdam Study[J]. Hepatology, 2022, 75(2): 419-429.
[4] Min HK, Cho H, Park SH. Pilot study: asymptomatic hyperuricemia patients with obesity and nonalcoholic fatty liver disease have increased risk of double contour sign[J]. Korean J Intern Med, 2020, 35(6): 1517.
[5] Yen PC, Chou YT, Li CH, et al. Hyperuricemia is associated with significant liver fibrosis in subjects with nonalcoholic fatty liver disease, but not in subjects without it[J]. J Clin Med, 2022, 11(5): 1445.
[6] Stefan N, Birkenfeld AL, Schulze MB.Global pandemics interconnected—obesity,impaired metabolic health and COVID-19[J].Nat Rev Endocrinol,2021,17(3): 135-149.
[7] Gutiérrez-Cuevas J, Santos A, Armendariz-Borunda J.Pathophysiological molecular mechanisms of obesity: a link between MAFLD and NASH with cardiovascular diseases[J].Int J Mol Sci, 2021, 22(21): 11629.
[8] Eslam M, Sarin SK, Wong VWS, et al.The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease[J].Hepatol Int, 2020, 14: 889-919.
[9] 中国居民肥胖防治专家共识[J].中国预防医学杂志,2022,23(05):321-339.
[10] 痛风及高尿酸血症中西医结合诊疗指南[J].中医杂志,2023,64(01):98-106.
[11] Zhou M, Yang N, Xing X, et al. Obesity interacts with hyperuricemia on the severity of non-alcoholic fatty liver disease[J]. BMC Gastroenterol, 2021, 21: 1-8.
[12] Brennan P, Clare K, George J, et al.Determining the role for uric acid in non-alcoholic steatohepatitis development and the utility of urate metabolites in diagnosis: an opinion review[J]. World J Gastroenterol, 2020, 26(15): 1683.
[13] Tang X, Shi Y, Du J, et al. Clinical outcome of non-alcoholic fatty liver disease: an 11-year follow-up study[J]. BMJ open, 2022, 12(6): e054891.
[14] Wijarnpreecha K, Panjawatanan P, Lekuthai N, et al. Hyperuricaemia and risk of nonalcoholic fatty liver disease: a meta-analysis[J].Liver Int, 2017, 37(6): 906-918.
[15] Yang C, He Q, Chen Z, et al. A bidirectional relationship between hyperuricemia and metabolic dysfunction-associated fatty liver disease[J]. Front Endocrinol,2022, 13.
[16] Golmohammadi S,Tavasoli M,Asadi N.Prevalence and risk factors of hyperuricemia in patients with chronic kidney disease and non-alcoholic fatty liver[J]. Clin Exp Gastroenterol, 2020: 299-304.
[17] Toledo-Ibelles P,Gutiérrez-Vidal R,Calixto-Tlacomulco S,et al.Hepatic accumulation of hypoxanthine: a link between hyperuricemia and nonalcoholic fatty liver disease[J].Arch Med Res, 2021, 52(7): 692-702.
[18] Lubawy M,Formanowicz D.High-fructose diet-induced hyperuricemia accompanying metabolic syndrome-mechanisms and dietary therapy proposals[J]. Int J Environ Res Public Health, 2023, 20(4): 3596.
[19] Abenavoli L, Di Renzo L, Boccuto L, et al. Health benefits of mediterranean diet in nonalcoholic fatty liver disease[J]. Expert Rev Gastroenterol Hepatol, 2018, 12(9): 873-881.
[20] Plaz Torres MC, Aghemo A, Lleo A, et al. Mediterranean diet and NAFLD: what we know and questions that still need to be answered[J].Nutrients,2019, 11(12): 2971.
[21] Xu K, Liu S, Zhao X, et al.Treating hyperuricemia related non-alcoholic fatty liver disease in rats with resveratrol[J]. Biomed Pharmacother, 2019, 110: 844-849.
[22] Zheng X, Gong L, Luo R, et al. Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults[J]. Lipids Health Dis, 2017, 16: 1-7.
[23] Ali N,Perveen R,Rahman S,et al.Prevalence of hyperuricemia and the relationship between serum uric acid and obesity:a study on Bangladeshi adults[J]. PloS one, 2018, 13(11): e0206850.
[24] Xie D, Zhao H, Lu J, et al.High uric acid induces liver fat accumulation via ROS/JNK/AP-1 signaling[J].Am J Physiol Endocrinol Metab,2021,320(6): E1032-E1043.
[25] Qi J, Ren X, Hou Y, et al. Triglyceride-glucose index is significantly associated with the risk of hyperuricemia in patients with nonalcoholic fatty liver disease[J]. Diabetes Metab Syndr Obes, 2023: 1323-1334.