Association between high sensitivity C-reactive protein and nonalcoholic fatty liver disease: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LIU Sifu ,  XIE Zhengyuan , TANG Shenglan , LAI Yueliang

Department of Gastroenterology, the Second Affiliated Hospital of Nanchang University, Nanchang 330002, P.R.China;

Corresponding author：

XIE Zhengyuan, Email: xzyxzy1230@163.com

Keywords：

Serum high sensitivity C-reactive protein; CRP; Nonalcoholic fatty liver disease; Meta-analysis; Systematic review; Case-control study

DOI：

10.7507/1672-2531.201912058

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objectives To systematically review the association between serum high sensitivity C-reactive protein (HS-CRP) and nonalcoholic fatty liver disease (NAFLD).Methods PubMed, EMbase, The Cochrane Library, CNKI, SinoMed and WanFang Data databases were electronically searched to collect case-control studies on the association between HS-CRP and NAFLD from inception to October, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Meta-analysis was then performed using RevMan 5.3 software.Results A total of 22 case-control studies involving 5 825 subjects were included. The results of meta-analysis showed that HS-CRP levels in NAFLD group were higher than non-NAFLD group (SMD=1.25, 95%CI 0.81 to 1.68, P<0.000 01). The results of subgroup analysis showed that, HS-CRP levels in NAFLD group were higher in Asian region (SMD=1.32, 95%CI 0.82 to 1.83, P<0.000 01), however not in American region (SMD=0.48, 95%CI −0.02 to 0.98, P=0.06). HS-CRP levels in NAFLD group were higher in BMI≥30 kg/m² group (SMD=0.37, 95%CI 0.19 to 0.54, P<0.000 1), however not in BMI<30 kg/m² group (SMD=1.19, 95%CI −0.28 to 2.66, P=0.11). Additionally, HS-CRP levels in NAFLD group were higher with or without diabetes (SMD=0.86, 95%CI 0.49 to 1.24, P<0.000 01; SMD=1.47, 95%CI 0.84 to 2.10, P<0.000 01).Conclusions Current evidence shows that NAFLD patients have higher levels of HS-CRP than non-NAFLD patients, and are affected by high levels of BMI and geographical regions. Therefore, HS-CRP may play important roles in the non-invasive field of NAFLD detection. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.

Citation： LIU Sifu, XIE Zhengyuan, TANG Shenglan, LAI Yueliang. Association between high sensitivity C-reactive protein and nonalcoholic fatty liver disease: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2020, 20(7): 769-775. doi: 10.7507/1672-2531.201912058 Copy

1.	Tanaka N, Kimura T, Fujimori N, et al. Current status, problems, and perspectives of non-alcoholic fatty liver disease research. World J Gastroenterol, 2019, 25(2): 163-177.
2.	Macut D, Božić-Antić I, Bjekić-Macut J, et al. Management of endocrine disease: Polycystic ovary syndrome and nonalcoholic fatty liver disease. Eur J Endocrinol, 2017, 177(3): R145-R158.
3.	Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American association for the study of liver diseases. Hepatology, 2018, 67(1): 328-357.
4.	Younossi ZM, Henry L, Bush H, et al. Clinical and economic burden of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis, 2018, 22(1): 1-10.
5.	Lee J, Yoon K, Ryu S, et al. High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men. PLoS One, 2017, 12(2): e0172666.
6.	Li Y, Zhong X, Cheng G, et al. Hs-CRP and all-cause, cardiovascular, and cancer mortality risk: A meta-analysis. Atherosclerosis, 2017, 259: 75-82.
7.	中华医学会肝病学分会脂肪肝和酒精性肝病学组. 非酒精性脂肪性肝病诊疗指南(2010年修订版). 中华肝脏病杂志, 2010, 18(3): 163-166.
8.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
9.	Kuppan G, Anjana RM, Deepa M, et al. Inflammatory markers in relation to nonalcoholic fatty liver disease in urban South Indians. Diabetes Technol Ther, 2012, 14(2): 152-158.
10.	熊甲英, 颜德中, 邝国兵. 非酒精性脂肪肝对血清C-反应蛋白及白细胞介素-6水平的影响. 实用医学杂志, 2009, 25(2): 334-335.
11.	Kim J, Lee DY, Park SE, et al. Increased risk for development of coronary artery calcification in subjects with non-alcoholic fatty liver disease and systemic inflammation. PLoS One, 2017, 12(7): e0180118.
12.	Boga S, Alkim H, Koksal AR, et al. Increased plasma levels of asymmetric dimethyl arginine in nonalcoholic fatty liver disease: relation with insulin resistance, inflammation, and liver histology. J Investig Med, 2015, 63(7): 871-877.
13.	Wu PB, Deng YZ, Shu YX, et al. Increased plasma CgA levels associated with nonalcoholic fatty liver disease. Turk J Gastroenterol, 2015, 26(5): 404-407.
14.	Bhatt SP, Nigam P, Misra A, et al. SREBP-2 1784 G/C genotype is associated with non-alcoholic fatty liver disease in north Indians. Dis Markers, 2011, 31(6): 371-377.
15.	Maleki I, Rastgar A, Hosseini V, et al. High sensitive CRP and pentraxine 3 as noninvasive biomarkers of nonalcoholic fatty liver disease. Eur Rev Med Pharmacol Sci, 2014, 18(11): 1583-1590.
16.	Ma YH, Zhao L, Xian XD, et al. A case-control study on the relationship between HDL2b and non-alcoholic fatty liver disease in Chinese type 2 diabetic patients. Clin Chem Lab Med, 2009, 47(9): 1067-1072.
17.	Karajamaki AJ, Patsi OP, Savolainen M, et al. Non-alcoholic fatty liver disease as a predictor of atrial fibrillation in middle-aged population (OPERA Study). PLoS One, 2015, 10(11): e0142937.
18.	Tan CH, Al-Kalifah N, Lee WJ, et al. HSCRP as surrogate marker in predicting long term effect of bariatric surgery on resolution of non-alcoholic steatohepatitis. Asian J Surg, 2019, 42(1): 203-208.
19.	Park SH, Kim BI, Yun JW, et al. Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men. J Gastroenterol Hepatol, 2004, 19(6): 694-698.
20.	朱庆曦, 邓长生. 非酒精性脂肪性肝病患者血清TNF-α、TGF-β1及hs-CRP的检测及意义. 世界华人消化杂志, 2008, 16(34): 3910-3912.
21.	易默, 周健, 吴友伟, 等. 老年非酒精性脂肪肝患者血脂载脂蛋白及炎症因子的变化研究. 山西医药杂志, 2017, 46(16): 1915-1917.
22.	马春静, 尉春苗, 邹薇. 老年非酒精性脂肪肝患者血清炎性因子水平及其临床意义. 中外医疗, 2019, 38(9): 189-191.
23.	彭朝阳, 盛晓燕, 彭朝胜. 幽门螺杆菌感染与非酒精性脂肪肝相关性研究. 医学研究杂志, 2014, 43(6): 153-156.
24.	阳琰, 高琳, 郝涛, 等. 餐后游离脂肪酸与2型糖尿病并原发性非酒精性脂肪肝的关系. 实用医学杂志, 2009, 25(22): 3810-3812.
25.	刘红, 林小红. 2型糖尿病合并非酒精性脂肪肝患者高敏C反应蛋白水平与大血管病变的相关性研究. 医学临床研究, 2011, 28(6): 1075-1077.
26.	王瑞雪, 姚远涛, 沙卫红, 等. 糖尿病合并非酒精性脂肪肝老年患者代谢及血管病变特点. 新医学, 2012, 43(7): 458-460.
27.	邱宇珍, 龙辉. 2型糖尿病并非酒精性脂肪性肝病患者炎症反应及氧化应激水平与动脉硬化的关系. 临床内科杂志, 2013, 30(2): 89-91.
28.	唐彬, 姚树坤. 非酒精性脂肪性肝炎患者血清L-FABP和TNF-α水平测定及其意义. 重庆医学, 2013, 42(15): 1696-1697, 1700.
29.	黄虹, 杨丕坚, 李舒敏, 等. Ⅱ型糖尿病伴非酒精性脂肪肝病患者炎症因子与内皮功能的改变. 西部医学, 2015, 27(4): 529-530, 533.
30.	金二荣, 王璐, 张洁, 等. 2型糖尿病合并非酒精性脂肪性肝病血浆chemerin与炎症指标的相关性. 天津医药, 2011, 39(8): 708-710.
31.	Mu W, Cheng XF, Liu Y, et al. Potential nexus of non-alcoholic fatty liver disease and type 2 diabetes mellitus: insulin resistance between hepatic and peripheral tissues. Front Pharmacol, 2019, 9: 1566.
32.	Uemura H, Katsuura-Kamano S, Yamaguchi M, et al. Relationships of serum high-sensitivity C-reactive protein and body size with insulin resistance in a Japanese cohort. PLoS One, 2017, 12(6): e0178672.
33.	Bian F, Yang XY, Xu G, et al. CRP-Induced NLRP3 Inflammasome activation increases LDL transcytosis across endothelial cells. Front Pharmacol, 2019, 10: 40.
34.	Tan HC, Yew TW, Chacko S, et al. Comprehensive assessment of insulin resistance in non-obese Asian Indian and Chinese men. J Diabetes Investig, 2018, 9(6): 1296-1303.
35.	Huffman FG, Whisner S, Zarini GG, et al. Waist circumference and BMI in relation to serum high sensitivity C-reactive protein (hs-CRP) in Cuban Americans with and without type 2 diabetes. Int J Environ Res Public Health, 2010, 7(3): 842-852.

1. Tanaka N, Kimura T, Fujimori N, et al. Current status, problems, and perspectives of non-alcoholic fatty liver disease research. World J Gastroenterol, 2019, 25(2): 163-177.
2. Macut D, Božić-Antić I, Bjekić-Macut J, et al. Management of endocrine disease: Polycystic ovary syndrome and nonalcoholic fatty liver disease. Eur J Endocrinol, 2017, 177(3): R145-R158.
3. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American association for the study of liver diseases. Hepatology, 2018, 67(1): 328-357.
4. Younossi ZM, Henry L, Bush H, et al. Clinical and economic burden of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis, 2018, 22(1): 1-10.
5. Lee J, Yoon K, Ryu S, et al. High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men. PLoS One, 2017, 12(2): e0172666.
6. Li Y, Zhong X, Cheng G, et al. Hs-CRP and all-cause, cardiovascular, and cancer mortality risk: A meta-analysis. Atherosclerosis, 2017, 259: 75-82.
7. 中华医学会肝病学分会脂肪肝和酒精性肝病学组. 非酒精性脂肪性肝病诊疗指南(2010年修订版). 中华肝脏病杂志, 2010, 18(3): 163-166.
8. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
9. Kuppan G, Anjana RM, Deepa M, et al. Inflammatory markers in relation to nonalcoholic fatty liver disease in urban South Indians. Diabetes Technol Ther, 2012, 14(2): 152-158.
10. 熊甲英, 颜德中, 邝国兵. 非酒精性脂肪肝对血清C-反应蛋白及白细胞介素-6水平的影响. 实用医学杂志, 2009, 25(2): 334-335.
11. Kim J, Lee DY, Park SE, et al. Increased risk for development of coronary artery calcification in subjects with non-alcoholic fatty liver disease and systemic inflammation. PLoS One, 2017, 12(7): e0180118.
12. Boga S, Alkim H, Koksal AR, et al. Increased plasma levels of asymmetric dimethyl arginine in nonalcoholic fatty liver disease: relation with insulin resistance, inflammation, and liver histology. J Investig Med, 2015, 63(7): 871-877.
13. Wu PB, Deng YZ, Shu YX, et al. Increased plasma CgA levels associated with nonalcoholic fatty liver disease. Turk J Gastroenterol, 2015, 26(5): 404-407.
14. Bhatt SP, Nigam P, Misra A, et al. SREBP-2 1784 G/C genotype is associated with non-alcoholic fatty liver disease in north Indians. Dis Markers, 2011, 31(6): 371-377.
15. Maleki I, Rastgar A, Hosseini V, et al. High sensitive CRP and pentraxine 3 as noninvasive biomarkers of nonalcoholic fatty liver disease. Eur Rev Med Pharmacol Sci, 2014, 18(11): 1583-1590.
16. Ma YH, Zhao L, Xian XD, et al. A case-control study on the relationship between HDL2b and non-alcoholic fatty liver disease in Chinese type 2 diabetic patients. Clin Chem Lab Med, 2009, 47(9): 1067-1072.
17. Karajamaki AJ, Patsi OP, Savolainen M, et al. Non-alcoholic fatty liver disease as a predictor of atrial fibrillation in middle-aged population (OPERA Study). PLoS One, 2015, 10(11): e0142937.
18. Tan CH, Al-Kalifah N, Lee WJ, et al. HSCRP as surrogate marker in predicting long term effect of bariatric surgery on resolution of non-alcoholic steatohepatitis. Asian J Surg, 2019, 42(1): 203-208.
19. Park SH, Kim BI, Yun JW, et al. Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men. J Gastroenterol Hepatol, 2004, 19(6): 694-698.
20. 朱庆曦, 邓长生. 非酒精性脂肪性肝病患者血清TNF-α、TGF-β1及hs-CRP的检测及意义. 世界华人消化杂志, 2008, 16(34): 3910-3912.
21. 易默, 周健, 吴友伟, 等. 老年非酒精性脂肪肝患者血脂载脂蛋白及炎症因子的变化研究. 山西医药杂志, 2017, 46(16): 1915-1917.
22. 马春静, 尉春苗, 邹薇. 老年非酒精性脂肪肝患者血清炎性因子水平及其临床意义. 中外医疗, 2019, 38(9): 189-191.
23. 彭朝阳, 盛晓燕, 彭朝胜. 幽门螺杆菌感染与非酒精性脂肪肝相关性研究. 医学研究杂志, 2014, 43(6): 153-156.
24. 阳琰, 高琳, 郝涛, 等. 餐后游离脂肪酸与2型糖尿病并原发性非酒精性脂肪肝的关系. 实用医学杂志, 2009, 25(22): 3810-3812.
25. 刘红, 林小红. 2型糖尿病合并非酒精性脂肪肝患者高敏C反应蛋白水平与大血管病变的相关性研究. 医学临床研究, 2011, 28(6): 1075-1077.
26. 王瑞雪, 姚远涛, 沙卫红, 等. 糖尿病合并非酒精性脂肪肝老年患者代谢及血管病变特点. 新医学, 2012, 43(7): 458-460.
27. 邱宇珍, 龙辉. 2型糖尿病并非酒精性脂肪性肝病患者炎症反应及氧化应激水平与动脉硬化的关系. 临床内科杂志, 2013, 30(2): 89-91.
28. 唐彬, 姚树坤. 非酒精性脂肪性肝炎患者血清L-FABP和TNF-α水平测定及其意义. 重庆医学, 2013, 42(15): 1696-1697, 1700.
29. 黄虹, 杨丕坚, 李舒敏, 等. Ⅱ型糖尿病伴非酒精性脂肪肝病患者炎症因子与内皮功能的改变. 西部医学, 2015, 27(4): 529-530, 533.
30. 金二荣, 王璐, 张洁, 等. 2型糖尿病合并非酒精性脂肪性肝病血浆chemerin与炎症指标的相关性. 天津医药, 2011, 39(8): 708-710.
31. Mu W, Cheng XF, Liu Y, et al. Potential nexus of non-alcoholic fatty liver disease and type 2 diabetes mellitus: insulin resistance between hepatic and peripheral tissues. Front Pharmacol, 2019, 9: 1566.
32. Uemura H, Katsuura-Kamano S, Yamaguchi M, et al. Relationships of serum high-sensitivity C-reactive protein and body size with insulin resistance in a Japanese cohort. PLoS One, 2017, 12(6): e0178672.
33. Bian F, Yang XY, Xu G, et al. CRP-Induced NLRP3 Inflammasome activation increases LDL transcytosis across endothelial cells. Front Pharmacol, 2019, 10: 40.
34. Tan HC, Yew TW, Chacko S, et al. Comprehensive assessment of insulin resistance in non-obese Asian Indian and Chinese men. J Diabetes Investig, 2018, 9(6): 1296-1303.
35. Huffman FG, Whisner S, Zarini GG, et al. Waist circumference and BMI in relation to serum high sensitivity C-reactive protein (hs-CRP) in Cuban Americans with and without type 2 diabetes. Int J Environ Res Public Health, 2010, 7(3): 842-852.

Chinese Journal of Evidence-Based Medicine

Association between high sensitivity C-reactive protein and nonalcoholic fatty liver disease: a meta-analysis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content