Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Meta-Analysis

Association of Cystatin C Level with All-cause Mortality in Patients with Liver Cirrhosis: A Meta-analysis

Author(s): Xiaoyan Wang, Wei Xu, Lin Yao, Yu Jie, Zhenjun Gao* and Yu Fan*

Volume 31, Issue 25, 2024

Published on: 02 January, 2024

Page: [3977 - 3986] Pages: 10

DOI: 10.2174/0109298673247263231123114043

Price: $65

Abstract

Background and Objective: Blood cystatin C level has been introduced as a promising biomarker to detect early kidney injury in cirrhotic patients. The purpose of this meta-analysis was to investigate the association of blood cystatin C level with allcause mortality in patients with liver cirrhosis.

Methods: PubMed, ScienceDirect, and Embase databases were searched from the inception to November 15, 2022. Observational studies evaluating the value of blood cystatin C level in predicting all-cause mortality in patients with ACS were selected. The pooled hazard risk (HR) with 95% confidence intervals (CI) was calculated using a random effect model meta-analysis.

Results: Twelve studies with 1983 cirrhotic patients were identified. The pooled adjusted HR of all-cause mortality was 3.59 (95% CI 2.39-5.39) for the high versus low group of cystatin C level. Stratified analysis by study design, characteristics of patients, geographical region, sample size, and length of follow-up further supported the predictive value elevated cystatin C level.

Conclusion: Elevated cystatin C level was an independent predictor of poor survival in patients with liver cirrhosis. Detection of blood cystatin C level may provide important prognostic information in cirrhotic patients.

Keywords: liver cirrhosis, cystatin C, all-cause mortality, meta-analysis, confidence intervals (CI), hazard risk (HR).

[1]
Fortea, J.I.; Crespo, J.; Puente, Á. Cirrhosis, a global and challenging disease. J. Clin. Med., 2022, 11(21), 6512.
[http://dx.doi.org/10.3390/jcm11216512] [PMID: 36362738]
[2]
Sepanlou, S.G.; Safiri, S.; Bisignano, C.; Ikuta, K.S.; Merat, S.; Saberifiroozi, M.; Poustchi, H.; Tsoi, D.; Colombara, D.V.; Abdoli, A.; Adedoyin, R.A.; Afarideh, M.; Agrawal, S.; Ahmad, S.; Ahmadian, E.; Ahmadpour, E.; Akinyemiju, T.; Akunna, C.J.; Alipour, V.; Almasi-Hashiani, A.; Almulhim, A.M.; Al-Raddadi, R.M.; Alvis-Guzman, N.; Anber, N.H.; Angus, C.; Anoushiravani, A.; Arabloo, J.; Araya, E.M.; Asmelash, D.; Ataeinia, B.; Ataro, Z.; Atout, M.M.W.; Ausloos, F.; Awasthi, A.; Badawi, A.; Banach, M.; Bejarano Ramirez, D.F.; Bhagavathula, A.S.; Bhala, N.; Bhattacharyya, K.; Biondi, A.; Bolla, S.R.; Boloor, A.; Borzì, A.M.; Butt, Z.A.; Cámera, L.L.A.A.; Campos-Nonato, I.R.; Carvalho, F.; Chu, D-T.; Chung, S-C.; Cortesi, P.A.; Costa, V.M.; Cowie, B.C.; Daryani, A.; de Courten, B.; Demoz, G.T.; Desai, R.; Dharmaratne, S.D.; Djalalinia, S.; Do, H.T.; Dorostkar, F.; Drake, T.M.; Dubey, M.; Duncan, B.B.; Effiong, A.; Eftekhari, A.; Elsharkawy, A.; Etemadi, A.; Farahmand, M.; Farzadfar, F.; Fernandes, E.; Filip, I.; Fischer, F.; Gebremedhin, K.B.B.; Geta, B.; Gilani, S.A.; Gill, P.S.; Gutirrez, R.A.; Haile, M.T.; Haj-Mirzaian, A.; Hamid, S.S.; Hasankhani, M.; Hasanzadeh, A.; Hashemian, M.; Hassen, H.Y.; Hay, S.I.; Hayat, K.; Heidari, B.; Henok, A.; Hoang, C.L.; Hostiuc, M.; Hostiuc, S.; Hsieh, V.C.; Igumbor, E.U.; Ilesanmi, O.S.; Irvani, S.S.N.; Jafari Balalami, N.; James, S.L.; Jeemon, P.; Jha, R.P.; Jonas, J.B.; Jozwiak, J.J.; Kabir, A.; Kasaeian, A.; Kassaye, H.G.; Kefale, A.T.; Khalilov, R.; Khan, M.A.; Khan, E.A.; Khater, A.; Kim, Y.J.; Koyanagi, A.; La Vecchia, C.; Lim, L-L.; Lopez, A.D.; Lorkowski, S.; Lotufo, P.A.; Lozano, R.; Magdy Abd El Razek, M.; Mai, H.T.; Manafi, N.; Manafi, A.; Mansournia, M.A.; Mantovani, L.G.; Mazzaglia, G.; Mehta, D.; Mendoza, W.; Menezes, R.G.; Mengesha, M.M.; Meretoja, T.J.; Mestrovic, T.; Miazgowski, B.; Miller, T.R.; Mirrakhimov, E.M.; Mithra, P.; Moazen, B.; Moghadaszadeh, M.; Mohammadian-Hafshejani, A.; Mohammed, S.; Mokdad, A.H.; Montero-Zamora, P.A.; Moradi, G.; Naimzada, M.D.; Nayak, V.; Negoi, I.; Nguyen, T.H.; Ofori-Asenso, R.; Oh, I-H.; Olagunju, T.O.; Padubidri, J.R.; Pakshir, K.; Pana, A.; Pathak, M.; Pourshams, A.; Rabiee, N.; Radfar, A.; Rafiei, A.; Ramezanzadeh, K.; Rana, S.M.M.; Rawaf, S.; Rawaf, D.L.; Reiner, R.C., Jr; Roever, L.; Room, R.; Roshandel, G.; Safari, S.; Samy, A.M.; Sanabria, J.; Sartorius, B.; Schmidt, M.I.; Senthilkumaran, S.; Shaikh, M.A.; Sharif, M.; Sharifi, A.; Shigematsu, M.; Singh, J.A.; Soheili, A.; Suleria, H.A.R.; Teklehaimanot, B.F.; Tesfay, B.E.; Vacante, M.; Vahedian-Azimi, A.; Valdez, P.R.; Vasankari, T.J.; Vu, G.T.; Waheed, Y.; Weldegwergs, K.G.; Werdecker, A.; Westerman, R.; Wondafrash, D.Z.; Wondmieneh, A.B.; Yeshitila, Y.G.; Yonemoto, N.; Yu, C.; Zaidi, Z.; Zarghi, A.; Zelber-Sagi, S.; Zewdie, K.A.; Zhang, Z-J.; Zhao, X-J.; Naghavi, M.; Malekzadeh, R. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol., 2020, 5(3), 245-266.
[http://dx.doi.org/10.1016/S2468-1253(19)30349-8] [PMID: 31981519]
[3]
Juanola, A.; Ma, A.T.; Pose, E.; Ginès, P. Novel biomarkers of AKI in cirrhosis. Semin. Liver Dis., 2022, 42(4), 489-500.
[http://dx.doi.org/10.1055/a-1954-4136] [PMID: 36191596]
[4]
Wong, F.; O’Leary, J.G.; Reddy, K.R.; Garcia-Tsao, G.; Fallon, M.B.; Biggins, S.W.; Subramanian, R.M.; Thuluvath, P.J.; Kamath, P.S.; Patton, H.; Maliakkal, B.; Tandon, P.; Vargas, H.; Thacker, L.; Bajaj, J.S. Acute kidney injury in cirrhosis: Baseline serum creatinine predicts patient outcomes. Am. J. Gastroenterol., 2017, 112(7), 1103-1110.
[http://dx.doi.org/10.1038/ajg.2017.122] [PMID: 28440305]
[5]
Wong, F. Acute kidney injury in liver cirrhosis: New definition and application. Clin. Mol. Hepatol., 2016, 22(4), 415-422.
[http://dx.doi.org/10.3350/cmh.2016.0056] [PMID: 27987536]
[6]
Yoo, J.J.; Kim, S.G.; Kim, Y.S.; Lee, B.; Lee, M.H.; Jeong, S.W.; Jang, J.Y.; Lee, S.H.; Kim, H.S.; Kim, Y.D.; Cheon, G.J. Estimation of renal function in patients with liver cirrhosis: Impact of muscle mass and sex. J. Hepatol., 2019, 70(5), 847-854.
[http://dx.doi.org/10.1016/j.jhep.2018.12.030] [PMID: 30630010]
[7]
Francoz, C.; Sola, E. Assessment of renal function in cirrhosis: Sarcopenia, gender and ethnicity matter. J. Hepatol., 2019, 70(5), 828-830.
[http://dx.doi.org/10.1016/j.jhep.2019.02.004] [PMID: 30833013]
[8]
Mussap, M.; Plebani, M. Biochemistry and clinical role of human cystatin C. Crit. Rev. Clin. Lab. Sci., 2004, 41(5-6), 467-550.
[http://dx.doi.org/10.1080/10408360490504934] [PMID: 15603510]
[9]
Shimizu-Tokiwa, A.; Kobata, M.; Io, H.; Kobayashi, N.; Shou, I.; Funabiki, K.; Fukui, M.; Horikoshi, S.; Shirato, I.; Saito, K.; Tomino, Y. Serum cystatin C is a more sensitive marker of glomerular function than serum creatinine. Nephron J., 2002, 92(1), 224-226.
[http://dx.doi.org/10.1159/000064453] [PMID: 12187109]
[10]
Seo, Y.S.; Jung, E.S.; An, H.; Kim, J.H.; Jung, Y.K.; Kim, J.H.; Yim, H.J.; Yeon, J.E.; Byun, K.S.; Kim, C.D.; Ryu, H.S.; Um, S.H. Serum cystatin C level is a good prognostic marker in patients with cirrhotic ascites and normal serum creatinine levels. Liver Int., 2009, 29(10), 1521-1527.
[http://dx.doi.org/10.1111/j.1478-3231.2009.02105.x] [PMID: 19725889]
[11]
Ahn, H.S.; Kim, Y.S.; Kim, S.G.; Kim, H.K.; Min, S.K.; Jeong, S.W.; Jang, J.Y.; Lee, S.H.; Kim, H.S.; Kim, B.S.; Park, J.M. Cystatin C is a good predictor of hepatorenal syndrome and survival in patients with cirrhosis who have normal serum creatinine levels. Hepatogastroenterology, 2012, 59(116), 1168-1173.
[PMID: 22057374]
[12]
Finkenstedt, A.; Dorn, L.; Edlinger, M.; Prokop, W.; Risch, L.; Griesmacher, A.; Graziadei, I.; Vogel, W.; Zoller, H. Cystatin C is a strong predictor of survival in patients with cirrhosis: Is a cystatin C -based MELD better? Liver Int., 2012, 32(8), 1211-1216.
[http://dx.doi.org/10.1111/j.1478-3231.2012.02766.x] [PMID: 22380485]
[13]
Maiwall, R.; Kumar, A.; Bhardwaj, A.; Kumar, G.; Bhadoria, A.S.; Sarin, S.K. Cystatin C predicts acute kidney injury and mortality in cirrhotics: A prospective cohort study. Liver Int., 2018, 38(4), 654-664.
[http://dx.doi.org/10.1111/liv.13600] [PMID: 28941301]
[14]
Seo, Y.S.; Park, S.Y.; Kim, M.Y.; Kim, S.G.; Park, J.Y.; Yim, H.J.; Jang, B.K.; Park, S.H.; Kim, J.H.; Suk, K.T.; Kim, J.D.; Kim, T.Y.; Cho, E.Y.; Lee, J.S.; Jung, S.W.; Jang, J.Y.; An, H.; Tak, W.Y.; Baik, S.K.; Hwang, J.S.; Kim, Y.S.; Sohn, J.H.; Um, S.H. Serum cystatin C level: An excellent predictor of mortality in patients with cirrhotic ascites. J. Gastroenterol. Hepatol., 2018, 33(4), 910-917.
[http://dx.doi.org/10.1111/jgh.13983] [PMID: 28910501]
[15]
Kim, T.H.; Lee, H.A.; Seo, Y.S.; Lee, Y.R.; Yim, S.Y.; Lee, Y.S.; Suh, S.J.; Jung, Y.K.; Kim, J.H.; An, H.; Yim, H.J.; Yeon, J.E.; Byun, K.S.; Um, S.H. Assessment and prediction of acute kidney injury in patients with decompensated cirrhosis with serum cystatin C and urine N-acetyl-β-D-glucosaminidase. J. Gastroenterol. Hepatol., 2019, 34(1), 234-240.
[http://dx.doi.org/10.1111/jgh.14387] [PMID: 30062791]
[16]
Torner, M.; Mangal, A.; Scharnagl, H.; Jansen, C.; Praktiknjo, M.; Queck, A.; Gu, W.; Schierwagen, R.; Lehmann, J.; Uschner, F.E.; Graf, C.; Strassburg, C.P.; Fernandez, J.; Stojakovic, T.; Woitas, R.; Trebicka, J. Sex specificity of kidney markers to assess prognosis in cirrhotic patients with TIPS. Liver Int., 2020, 40(1), 186-193.
[http://dx.doi.org/10.1111/liv.14230] [PMID: 31448496]
[17]
Padia, G.; Mahajan, B.; Kumar, A.; Sonika, U.; Dahale, A.S.; Sachdeva, S.; Dalal, A.; George, R. Cystatin C and interleukin-6 for prognosticating patients with acute decompensation of cirrhosis. JGH Open, 2021, 5(4), 459-464.
[http://dx.doi.org/10.1002/jgh3.12516] [PMID: 33860096]
[18]
Jo, S.K.; Yang, J.; Hwang, S.M.; Lee, M.S.; Park, S.H. Role of biomarkers as predictors of acute kidney injury and mortality in decompensated cirrhosis. Sci. Rep., 2019, 9(1), 14508.
[http://dx.doi.org/10.1038/s41598-019-51053-8] [PMID: 31601879]
[19]
Abd El Wahab, A.M.; Awadeen, A.; Mansour, M.M.; Shemies, R. The diagnostic and prognostic utility of serum cystatin C and angiopoietin 2 in patients with liver cirrhosis complicated by acute kidney injury. Ther. Apher. Dial., 2022.
[PMID: 36181409]
[20]
Moher, D; Liberati, A; Tetzlaff, J; Altman, DG Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann. Intern. Med., 2009, 151(4), 264-9.
[21]
Wells, G.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M. The Newcastle–Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
[22]
Fahmy, O.; Fahmy, U.A.; Alhakamy, N.A.; Khairul-Asri, M.G. Single-port versus multiple-port robot-assisted radical prostatectomy: A systematic review and meta-analysis. J. Clin. Med., 2021, 10(24), 5723.
[http://dx.doi.org/10.3390/jcm10245723] [PMID: 34945018]
[23]
Aumpan, N; Limprukkasem, T; Pornthisarn, B; Vilaichone, RK; Chonprasertsuk, S; Bhanthumkomol, P Plasma Cystatin C level is a prognostic marker of morbidity and mortality in hospitalized decompensated cirrhotic patients. J. Med. Invest., 2021, 68(3.4), 302-8.
[24]
Grant, R.L. Converting an odds ratio to a range of plausible relative risks for better communication of research findings. BMJ, 2014, 348(jan24 1), f7450.
[http://dx.doi.org/10.1136/bmj.f7450] [PMID: 24464277]
[25]
Begg, C.B.; Mazumdar, M. Operating characteristics of a rank correlation test for publication bias. Biometrics, 1994, 50(4), 1088-1101.
[http://dx.doi.org/10.2307/2533446] [PMID: 7786990]
[26]
Egger, M.; Smith, G.D.; Schneider, M.; Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109), 629-634.
[http://dx.doi.org/10.1136/bmj.315.7109.629] [PMID: 9310563]
[27]
Wu, J.; Wu, Q.; Wu, M.; Mao, W. Serum cystatin C predicts mortality in HBV-related decompensated cirrhosis. BioMed Res. Int., 2019, 2019, 1-6.
[http://dx.doi.org/10.1155/2019/7272045] [PMID: 30949507]
[28]
Mauro, E.; Crespo, G.; Martinez-Garmendia, A.; Gutierrez-Acevedo, M.N.; Diaz, J.M.; Saidman, J.; Bermudez, C.; Ortiz-Patron, J.; Garcia-Olveira, L.; Zalazar, F.; Narvaez, A.; Spina, J.C.; Orta, R.; Savluk, L.; Piano, S.; Marciano, S.; Gadano, A. Cystatin C and sarcopenia predict acute on chronic liver failure development and mortality in patients on the liver transplant waiting list. Transplantation, 2020, 104(7), e188-e198.
[http://dx.doi.org/10.1097/TP.0000000000003222] [PMID: 32150034]
[29]
Suksamai, A.; Chaiprasert, A.; Chirapongsathorn, S. Serum cystatin C as a predictor of 90-day mortality among patients admitted with complications of cirrhosis. JGH Open, 2021, 5(5), 607-613.
[http://dx.doi.org/10.1002/jgh3.12543] [PMID: 34013062]
[30]
Luo, J.; Wang, L.P.; Hu, H.F.; Zhang, L.; Li, Y.L.; Ai, L.M.; Mu, H.Y.; Kun-Wang Cystatin C and cardiovascular or all-cause mortality risk in the general population: A meta-analysis. Clin. Chim. Acta, 2015, 450, 39-45.
[http://dx.doi.org/10.1016/j.cca.2015.07.016] [PMID: 26192218]
[31]
Yang, S.; Song, L.; Zhao, L.; Dong, P.; Lai, L.; Wang, H. Predictive value of cystatin C in people with suspected or established coronary artery disease: A meta-analysis. Atherosclerosis, 2017, 263, 60-67.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.05.025] [PMID: 28599259]
[32]
Sun, Y.; Lu, Q.; Cheng, B.; Tao, X. Prognostic value of cystatin C in patients with acute coronary syndrome: A systematic review and meta-analysis. Eur. J. Clin. Invest., 2021, 51(3), e13440.
[http://dx.doi.org/10.1111/eci.13440] [PMID: 33128232]
[33]
Karvellas, C.J.; Durand, F.; Nadim, M.K. Acute kidney injury in cirrhosis. Crit. Care Clin., 2015, 31(4), 737-750.
[http://dx.doi.org/10.1016/j.ccc.2015.06.009] [PMID: 26410141]
[34]
Markwardt, D.; Holdt, L.; Steib, C.; Benesic, A.; Bendtsen, F.; Bernardi, M.; Moreau, R.; Teupser, D.; Wendon, J.; Nevens, F.; Trebicka, J.; Garcia, E.; Pavesi, M.; Arroyo, V.; Gerbes, A.L. Plasma cystatin C is a predictor of renal dysfunction, acute-on-chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis. Hepatology, 2017, 66(4), 1232-1241.
[http://dx.doi.org/10.1002/hep.29290] [PMID: 28545169]
[35]
Francoz, C.; Glotz, D.; Moreau, R.; Durand, F. The evaluation of renal function and disease in patients with cirrhosis. J. Hepatol., 2010, 52(4), 605-613.
[http://dx.doi.org/10.1016/j.jhep.2009.11.025] [PMID: 20185192]
[36]
Shlipak, M.G.; Katz, R.; Cushman, M.; Sarnak, M.J.; Stehman-Breen, C.; Psaty, B.M.; Siscovick, D.; Tracy, R.P.; Newman, A.; Fried, L. Cystatin-C and inflammatory markers in the ambulatory elderly. Am. J. Med., 2005, 118(12), 1416.e25-1416.e31.
[http://dx.doi.org/10.1016/j.amjmed.2005.07.060] [PMID: 16378798]
[37]
Mahassadi, A.K.; Konang, J.N.; Kissi, H.Y.; Afum-Adjei Awuah, A.; Bangoura, A.D.; Doffou, S.A.; Attia, A.K. Systemic inflammatory response syndrome and model for end-stage liver disease score accurately predict the in-hospital mortality of black African patients with decompensated cirrhosis at initial hospitalization: A retrospective cohort study. Clin. Exp. Gastroenterol., 2018, 11, 143-152.
[http://dx.doi.org/10.2147/CEG.S140655] [PMID: 29670387]
[38]
Yang, D.; Xie, Y.; Pan, H.; Huang, Y.; Dai, Y.; Tong, Y.; Chen, M. Clinical characteristics and prognostic factors of liver cirrhosis patients with systemic inflammatory response syndrome. Hepatol. Res., 2017, 47(11), 1174-1185.
[http://dx.doi.org/10.1111/hepr.12886] [PMID: 28249358]
[39]
Ladero, J.M.; Cárdenas, M.C.; Ortega, L.; González-Pino, A.; Cuenca, F.; Morales, C.; Lee-Brunner, A. Serum cystatin C: A non-invasive marker of liver fibrosis or of current liver fibrogenesis in chronic hepatitis C? Ann. Hepatol., 2012, 11(5), 648-651.
[http://dx.doi.org/10.1016/S1665-2681(19)31437-1] [PMID: 22947524]
[40]
Torre, A.; Aguirre-Valadez, J.M.; Arreola-Guerra, J.M.; García-Flores, O.R.; García-Juárez, I.; Cruz-Rivera, C.; Correa-Rotter, R.; Niño-Cruz, J.A. Creatinine versus cystatin C for estimating GFR in patients with liver cirrhosis. Am. J. Kidney Dis., 2016, 67(2), 342-344.
[http://dx.doi.org/10.1053/j.ajkd.2015.09.022] [PMID: 26530874]
[41]
Carrier, P.; Debette-Gratien, M.; Essig, M.; Loustaud-Ratti, V. Beyond serum creatinine: which tools to evaluate renal function in cirrhotic patients? Hepatol. Res., 2018, 48(10), 771-779.
[http://dx.doi.org/10.1111/hepr.13224] [PMID: 29954046]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy