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：

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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, Bo?i?-Anti? I, Bjeki?-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.	中華醫學會肝病學分會脂肪肝和酒精性肝病學組. 非酒精性脂肪性肝病診療指南(2010年修訂版). 中華肝臟病雜志, 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, 顏德中, 鄺國兵. 非酒精性脂肪肝對血清C-反應蛋白及白細胞介素-6水平的影響. 實用醫學雜志, 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.	朱慶曦, 鄧長生. 非酒精性脂肪性肝病患者血清TNF-α、TGF-β1及hs-CRP的檢測及意義. 世界華人消化雜志, 2008, 16(34): 3910-3912.
21.	易默, 周健, 吳友偉, 等. 老年非酒精性脂肪肝患者血脂載脂蛋白及炎癥因子的變化研究. 山西醫藥雜志, 2017, 46(16): 1915-1917.
22.	馬春靜, 尉春苗, 鄒薇. 老年非酒精性脂肪肝患者血清炎性因子水平及其臨床意義. 中外醫療, 2019, 38(9): 189-191.
23.	彭朝陽, 盛曉燕, 彭朝勝. 幽門螺桿菌感染與非酒精性脂肪肝相關性研究. 醫學研究雜志, 2014, 43(6): 153-156.
24.	陽琰, 高琳, 郝濤, 等. 餐后游離脂肪酸與2型糖尿病并原發性非酒精性脂肪肝的關系. 實用醫學雜志, 2009, 25(22): 3810-3812.
25.	劉紅, 林小紅. 2型糖尿病合并非酒精性脂肪肝患者高敏C反應蛋白水平與大血管病變的相關性研究. 醫學臨床研究, 2011, 28(6): 1075-1077.
26.	王瑞雪, 姚遠濤, 沙衛紅, 等. 糖尿病合并非酒精性脂肪肝老年患者代謝及血管病變特點. 新醫學, 2012, 43(7): 458-460.
27.	邱宇珍, 龍輝. 2型糖尿病并非酒精性脂肪性肝病患者炎癥反應及氧化應激水平與動脈硬化的關系. 臨床內科雜志, 2013, 30(2): 89-91.
28.	唐彬, 姚樹坤. 非酒精性脂肪性肝炎患者血清L-FABP和TNF-α水平測定及其意義. 重慶醫學, 2013, 42(15): 1696-1697, 1700.
29.	黃虹, 楊丕堅, 李舒敏, 等. Ⅱ型糖尿病伴非酒精性脂肪肝病患者炎癥因子與內皮功能的改變. 西部醫學, 2015, 27(4): 529-530, 533.
30.	金二榮, 王璐, 張潔, 等. 2型糖尿病合并非酒精性脂肪性肝病血漿chemerin與炎癥指標的相關性. 天津醫藥, 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, Bo?i?-Anti? I, Bjeki?-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. 中華醫學會肝病學分會脂肪肝和酒精性肝病學組. 非酒精性脂肪性肝病診療指南(2010年修訂版). 中華肝臟病雜志, 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, 顏德中, 鄺國兵. 非酒精性脂肪肝對血清C-反應蛋白及白細胞介素-6水平的影響. 實用醫學雜志, 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. 朱慶曦, 鄧長生. 非酒精性脂肪性肝病患者血清TNF-α、TGF-β1及hs-CRP的檢測及意義. 世界華人消化雜志, 2008, 16(34): 3910-3912.
21. 易默, 周健, 吳友偉, 等. 老年非酒精性脂肪肝患者血脂載脂蛋白及炎癥因子的變化研究. 山西醫藥雜志, 2017, 46(16): 1915-1917.
22. 馬春靜, 尉春苗, 鄒薇. 老年非酒精性脂肪肝患者血清炎性因子水平及其臨床意義. 中外醫療, 2019, 38(9): 189-191.
23. 彭朝陽, 盛曉燕, 彭朝勝. 幽門螺桿菌感染與非酒精性脂肪肝相關性研究. 醫學研究雜志, 2014, 43(6): 153-156.
24. 陽琰, 高琳, 郝濤, 等. 餐后游離脂肪酸與2型糖尿病并原發性非酒精性脂肪肝的關系. 實用醫學雜志, 2009, 25(22): 3810-3812.
25. 劉紅, 林小紅. 2型糖尿病合并非酒精性脂肪肝患者高敏C反應蛋白水平與大血管病變的相關性研究. 醫學臨床研究, 2011, 28(6): 1075-1077.
26. 王瑞雪, 姚遠濤, 沙衛紅, 等. 糖尿病合并非酒精性脂肪肝老年患者代謝及血管病變特點. 新醫學, 2012, 43(7): 458-460.
27. 邱宇珍, 龍輝. 2型糖尿病并非酒精性脂肪性肝病患者炎癥反應及氧化應激水平與動脈硬化的關系. 臨床內科雜志, 2013, 30(2): 89-91.
28. 唐彬, 姚樹坤. 非酒精性脂肪性肝炎患者血清L-FABP和TNF-α水平測定及其意義. 重慶醫學, 2013, 42(15): 1696-1697, 1700.
29. 黃虹, 楊丕堅, 李舒敏, 等. Ⅱ型糖尿病伴非酒精性脂肪肝病患者炎癥因子與內皮功能的改變. 西部醫學, 2015, 27(4): 529-530, 533.
30. 金二榮, 王璐, 張潔, 等. 2型糖尿病合并非酒精性脂肪性肝病血漿chemerin與炎癥指標的相關性. 天津醫藥, 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

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