Role of systemic inflammation in cirrhosis: From pathogenesis to prognosis

World Journal of Hepatology

Volumn 7, Issue 16, 2015, Pages 1974-1981

  Dirchwolf, Melisa ^a   Ruf, Andrés Eduardo ^b,c  

^a HOSPITAL F J MUÑIZ   (Argentina)

^b FUNDIEH Fundación para la Docencia e Investigación de las Enfermedades del Hígado   (Argentina)

^c HOSPITAL BRITÁNICO DE BUENOS AIRES   (Argentina)

Author keywords

Acute onchronic liver failure; Cirrhosis; Immune dysfunction; Prognosis; Systemic inflammation

Indexed keywords

EID: 84938887319     PISSN: None     EISSN: 19485182     Source Type: Journal    
DOI: 10.4254/wjh.v7.i16.1974     Document Type: Editorial

References (71)

1. Asrani SK, Kamath PS. Natural history of cirrhosis. Curr Gastroenterol Rep 2013; 15: 308 [PMID: 23314828 DOI: 10.1007/s11894-012-0308-y]
2. D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006; 44: 217-231 [PMID: 16298014 DOI: 10.1016/j.jhep.2005.10.013]
3. Jalan R, Gines P, Olson JC, Mookerjee RP, Moreau R, Garcia-Tsao G, Arroyo V, Kamath PS. Acute-on chronic liver failure. J Hepatol 2012; 57: 1336-1348 [PMID: 22750750 DOI: 10.1016/j. jhep.2012.06.026]
4. Moreau R, Arroyo V. Acute-on-chronic liver failure: a new clinical entity. Clin Gastroenterol Hepatol 2015; 13: 836-841 [PMID: 24583872 DOI: 10.1016/j.cgh.2014.02.027]
5. Arroyo V, García-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol 2014; 61: 396-407 [PMID: 24751830 DOI: 10.1016/j.jhep.2014.04.012]
6. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol 2014; 61: 1385-1396 [PMID: 25135860 DOI: 10.1016/j.jhep.2014.08.010]
7. Garcia-Tsao G, Friedman S, Iredale J, Pinzani M. Now there are many (stages) where before there was one: In search of a pathophysiological classification of cirrhosis. Hepatology 2010; 51: 1445-1449 [PMID: 20077563 DOI: 10.1002/hep.23478]
8. Albilllos A, Garcia-Tsao G. Classification of cirrhosis: the clinical use of HVPG measurements. Dis Markers 2011; 31: 121-128 [PMID: 22045397 DOI: 10.3233/dma-2011-0834]
9. de Franchis R, Primignani M. Natural history of portal hypertension in patients with cirrhosis. Clin Liver Dis 2001; 5: 645-663 [PMID: 11565135]
10. European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 2010; 53: 397-417 [PMID: 20633946 DOI: 10.1016/j.jhep.2010.05.004]
11. Ripoll C, Groszmann R, Garcia-Tsao G, Grace N, Burroughs A, Planas R, Escorsell A, Garcia-Pagan JC, Makuch R, Patch D, Matloff DS, Bosch J. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology 2007; 133: 481-488 [PMID: 17681169 DOI: 10.1053/j.gastro.2007.05.024]
12. Dienstag JL, Ghany MG, Morgan TR, Di Bisceglie AM, Bonkovsky HL, Kim HY, Seeff LB, Szabo G, Wright EC, Sterling RK, Everson GT, Lindsay KL, Lee WM, Lok AS, Morishima C, Stoddard AM, Everhart JE. A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C. Hepatology 2011; 54: 396-405 [PMID: 21520194 DOI: 10.1002/hep.24370]
13. Bruns T, Zimmermann HW, Stallmach A. Risk factors and outcome of bacterial infections in cirrhosis. World J Gastroenterol 2014; 20: 2542-2554 [PMID: 24627590 DOI: 10.3748/wjg.v20. i10.2542]
14. Arvaniti V, D'Amico G, Fede G, Manousou P, Tsochatzis E, Pleguezuelo M, Burroughs AK. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology 2010; 139: 1246-1256, 1256.e1-e5 [PMID: 20558165 DOI: 10.1053/j.gastro.2010.06.019]
15. Tandon P, Garcia-Tsao G. Bacterial infections, sepsis, and multiorgan failure in cirrhosis. Semin Liver Dis 2008; 28: 26-42 [PMID: 18293275 DOI: 10.1055/s-2008-1040319]
16. Arroyo V, Moreau R, Jalan R, Ginès P. Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis. J Hepatol 2015; 62: S131-S143 [PMID: 25920082 DOI: 10.1016/j. jhep.2014.11.045]
17. Asrani SK, O'Leary JG. Acute-on-chronic liver failure. Clin Liver Dis 2014; 18: 561-574 [PMID: 25017076 DOI: 10.1016/j.cld.2014.05.004]
18. Jalan R, Pavesi M, Saliba F, Amorós A, Fernandez J, Holland-Fischer P, Sawhney R, Mookerjee R, Caraceni P, Moreau R, Ginès P, Durand F, Angeli P, Alessandria C, Laleman W, Trebicka J, Samuel D, Zeuzem S, Gustot T, Gerbes AL, Wendon J, Bernardi M, Arroyo V. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acuteon- chronic liver failure. J Hepatol 2015; 62: 831-840 [PMID: 25463539 DOI: 10.1016/j.jhep.2014.11.012]
19. Planas R, Ballesté B, Alvarez MA, Rivera M, Montoliu S, Galeras JA, Santos J, Coll S, Morillas RM, Solà R. Natural history of decompensated hepatitis C virus-related cirrhosis. A study of 200 patients. J Hepatol 2004; 40: 823-830 [PMID: 15094231 DOI: 10.1016/j.jhep.2004.01.005]
20. Yi ZQ, Lu MH, Xu XW, Fu XY, Tan DM. A novel prognostic score for acute-on-chronic hepatitis B liver failure. J Huazhong Univ Sci Technolog Med Sci 2015; 35: 87-92 [PMID: 25673199 DOI: 10.1007/s11596-015-1394-5]
21. Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M, Zhang S, Xu Z, Wu Y, Yan H, Chen Z. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 2015; 62: 232-242 [PMID: 25800029 DOI: 10.1002/hep.27795]
22. Giannelli V, Di Gregorio V, Iebba V, Giusto M, Schippa S, Merli M, Thalheimer U. Microbiota and the gut-liver axis: bacterial translocation, inflammation and infection in cirrhosis. World J Gastroenterol 2014; 20: 16795-16810 [PMID: 25492994 DOI: 10.3748/wjg.v20.i45.16795]
23. Sipeki N, Antal-Szalmas P, Lakatos PL, Papp M. Immune dysfunction in cirrhosis. World J Gastroenterol 2014; 20: 2564-2577 [PMID: 24627592 DOI: 10.3748/wjg.v20.i10.2564]
24. Selmi C, Mackay IR, Gershwin ME. The immunological milieu of the liver. Semin Liver Dis 2007; 27: 129-139 [PMID: 17520513 DOI: 10.1055/s-2007-979466]
25. Aoyama T, Paik YH, Seki E. Toll-like receptor signaling and liver fibrosis. Gastroenterol Res Pract 2010; 2010: pii: 192543 [PMID: 20706677 DOI: 10.1155/2010/192543]
26. Nakamoto N, Kanai T. Role of toll-like receptors in immune activation and tolerance in the liver. Front Immunol 2014; 5: 221 [PMID: 24904576 DOI: 10.3389/fimmu.2014.00221]
27. Wiest R, Lawson M, Geuking M. Pathological bacterial translocation in liver cirrhosis. J Hepatol 2014; 60: 197-209 [PMID: 23993913 DOI: 10.1016/j.jhep.2013.07.044]
28. Muñoz L, José Borrero M, Ubeda M, Lario M, Díaz D, Francés R, Monserrat J, Pastor O, Aguado-Fraile E, Such J, Alvarez-Mon M, Albillos A. Interaction between intestinal dendritic cells and bacteria translocated from the gut in rats with cirrhosis. Hepatology 2012; 56: 1861-1869 [PMID: 22611024 DOI: 10.1002/hep.25854]
29. Garcia-Tsao G, Lee FY, Barden GE, Cartun R, West AB. Bacterial translocation to mesenteric lymph nodes is increased in cirrhotic rats with ascites. Gastroenterology 1995; 108: 1835-1841 [PMID: 7768390]
30. Garcia-Tsao G, Wiest R. Gut microflora in the pathogenesis of the complications of cirrhosis. Best Pract Res Clin Gastroenterol 2004; 18: 353-372 [PMID: 15123075 DOI: 10.1016/j.bpg.2003.10.005]
31. Knolle PA, Gerken G. Local control of the immune response in the liver. Immunol Rev 2000; 174: 21-34 [PMID: 10807504]
32. Shawcross DL. Is it time to target gut dysbiosis and immune dysfunction in the therapy of hepatic encephalopathy? Expert Rev Gastroenterol Hepatol 2015; 9: 539-542 [PMID: 25846450 DOI: 10.1586/17474124.2015.1035257]
33. Wiest R, Das S, Cadelina G, Garcia-Tsao G, Milstien S, Groszmann RJ. Bacterial translocation in cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility. J Clin Invest 1999; 104: 1223-1233 [PMID: 10545521 DOI: 10.1172/jci7458]
34. Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology 2005; 41: 422-433 [PMID: 15723320 DOI: 10.1002/hep.20632]
35. Tritto G, Bechlis Z, Stadlbauer V, Davies N, Francés R, Shah N, Mookerjee RP, Such J, Jalan R. Evidence of neutrophil functional defect despite inflammation in stable cirrhosis. J Hepatol 2011; 55: 574-581 [PMID: 21236309 DOI: 10.1016/j.jhep.2010.11.034]
36. Mookerjee RP, Stadlbauer V, Lidder S, Wright GA, Hodges SJ, Davies NA, Jalan R. Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome. Hepatology 2007; 46: 831-840 [PMID: 17680644 DOI: 10.1002/hep.21737]
37. Fagan KJ, Rogers GB, Melino M, Arthur DM, Costello ME, Morrison M, Powell EE, Irvine KM. Ascites bacterial burden and immune cell profile are associated with poor clinical outcomes in the absence of overt infection. PLoS One 2015; 10: e0120642 [PMID: 25781164 DOI: 10.1371/journal.pone.0120642]
38. Bernsmeier C, Pop OT, Singanayagam A, Triantafyllou E, Patel VC, Weston CJ, Curbishley S, Sadiq F, Vergis N, Khamri W, Bernal W, Auzinger G, Heneghan M, Ma Y, Jassem W, Heaton ND, Adams DH, Quaglia A, Thursz MR, Wendon J, Antoniades CG. Patients with acute-on-chronic liver failure have increased numbers of regulatory immune cells expressing the receptor tyrosine kinase MERTK. Gastroenterology 2015; 148: 603-615.e14 [PMID: 25479139 DOI: 10.1053/j.gastro.2014.11.045]
39. Yee RM, Lehil MS, Rongey C, Shen H, Cozen ML, Monto A, Ryan JC. Impaired lymphocyte reactivity measured by immune function testing in untransplanted patients with cirrhosis. Clin Vaccine Immunol 2013; 20: 526-529 [PMID: 23389930 DOI: 10.1128/cvi.00595-12]
40. Tiegs G, Lohse AW. Immune tolerance: what is unique about the liver. J Autoimmun 2010; 34: 1-6 [PMID: 19717280 DOI: 10.1016/j.jaut.2009.08.008]
41. Leber B, Spindelboeck W, Stadlbauer V. Infectious complications of acute and chronic liver disease. Semin Respir Crit Care Med 2012; 33: 80-95 [PMID: 22447263 DOI: 10.1055/s-0032-1301737]
42. Wong F, Bernardi M, Balk R, Christman B, Moreau R, Garcia-Tsao G, Patch D, Soriano G, Hoefs J, Navasa M. Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club. Gut 2005; 54: 718-725 [PMID: 15831923 DOI: 10.1136/gut.2004.038679]
43. Jalan R, Fernandez J, Wiest R, Schnabl B, Moreau R, Angeli P, Stadlbauer V, Gustot T, Bernardi M, Canton R, Albillos A, Lammert F, Wilmer A, Mookerjee R, Vila J, Garcia-Martinez R, Wendon J, Such J, Cordoba J, Sanyal A, Garcia-Tsao G, Arroyo V, Burroughs A, Ginès P. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol 2014; 60: 1310-1324 [PMID: 24530646 DOI: 10.1016/j.jhep.2014.01.024]
44. Fukui H. Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia. World J Hepatol 2015; 7: 425-442 [PMID: 25848468 DOI: 10.4254/wjh.v7.i3.425]
45. Ilan Y. Leaky gut and the liver: a role for bacterial translocation in nonalcoholic steatohepatitis. World J Gastroenterol 2012; 18: 2609-2618 [PMID: 22690069 DOI: 10.3748/wjg.v18.i21.2609]
46. Lutz P, Nischalke HD, Strassburg CP, Spengler U. Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver. World J Hepatol 2015; 7: 304-314 [PMID: 25848460 DOI: 10.4254/wjh.v7.i3.304]
47. Seo YS, Shah VH. The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension. Clin Mol Hepatol 2012; 18: 337-346 [PMID: 23323248 DOI: 10.3350/cmh.2012.18.4.337]
48. Attar BM, Moore CM, George M, Ion-Nedelcu N, Turbay R, Zachariah A, Ramadori G, Fareed J, Van Thiel DH. Procalcitonin, and cytokines document a dynamic inflammatory state in noninfected cirrhotic patients with ascites. World J Gastroenterol 2014; 20: 2374-2382 [PMID: 24605035 DOI: 10.3748/wjg.v20.i9.2374]
49. Wasmuth HE, Kunz D, Yagmur E, Timmer-Stranghöner A, Vidacek D, Siewert E, Bach J, Geier A, Purucker EA, Gressner AM, Matern S, Lammert F. Patients with acute on chronic liver failure display "sepsis-like" immune paralysis. J Hepatol 2005; 42: 195-201 [PMID: 15664244 DOI: 10.1016/j.jhep.2004.10.019]
50. Romero-Gómez M, Montagnese S, Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol 2015; 62: 437-447 [PMID: 25218789 DOI: 10.1016/j.jhep.2014.09.005]
51. Mehta G, Mookerjee RP, Sharma V, Jalan R. Systemic inflammation is associated with increased intrahepatic resistance and mortality in alcohol-related acute-on-chronic liver failure. Liver Int 2015; 35: 724-734 [PMID: 24703488 DOI: 10.1111/liv.12559]
52. Karagiannakis DS, Vlachogiannakos J, Anastasiadis G, Vafiadis-Zouboulis I, Ladas SD. Frequency and severity of cirrhotic cardiomyopathy and its possible relationship with bacterial endotoxemia. Dig Dis Sci 2013; 58: 3029-3036 [PMID: 23907333 DOI: 10.1007/s10620-013-2693-y]
53. Shah N, Dhar D, El Zahraa Mohammed F, Habtesion A, Davies NA, Jover-Cobos M, Macnaughtan J, Sharma V, Olde Damink SW, Mookerjee RP, Jalan R. Prevention of acute kidney injury in a rodent model of cirrhosis following selective gut decontamination is associated with reduced renal TLR4 expression. J Hepatol 2012; 56: 1047-1053 [PMID: 22266601 DOI: 10.1016/j. jhep.2011.11.024]
54. Thabut D, Massard J, Gangloff A, Carbonell N, Francoz C, Nguyen-Khac E, Duhamel C, Lebrec D, Poynard T, Moreau R. Model for end-stage liver disease score and systemic inflammatory response are major prognostic factors in patients with cirrhosis and acute functional renal failure. Hepatology 2007; 46: 1872-1882 [PMID: 17972337 DOI: 10.1002/hep.21920]
55. Cazzaniga M, Dionigi E, Gobbo G, Fioretti A, Monti V, Salerno F. The systemic inflammatory response syndrome in cirrhotic patients: relationship with their in-hospital outcome. J Hepatol 2009; 51: 475-482 [PMID: 19560225 DOI: 10.1016/j. jhep.2009.04.017]
56. Abdel-Khalek EE, El-Fakhry A, Helaly M, Hamed M, Elbaz O. Systemic inflammatory response syndrome in patients with liver cirrhosis. Arab J Gastroenterol 2011; 12: 173-177 [PMID: 22305496 DOI: 10.1016/j.ajg.2011.11.006]
57. Behroozian R, Bayazidchi M, Rasooli J. Systemic Inflammatory Response Syndrome and MELD Score in Hospital Outcome of Patients with Liver Cirrhosis. Middle East J Dig Dis 2012; 4: 168-172 [PMID: 24829652]
58. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, Gustot T, Saliba F, Domenicali M, Gerbes A, Wendon J, Alessandria C, Laleman W, Zeuzem S, Trebicka J, Bernardi M, Arroyo V. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013; 144: 1426-1437, 1437.e1-e9 [PMID: 23474284 DOI: 10.1053/j.gastro.2013.02.042]
59. Bajaj JS, O'Leary JG, Reddy KR, Wong F, Biggins SW, Patton H, Fallon MB, Garcia-Tsao G, Maliakkal B, Malik R, Subramanian RM, Thacker LR, Kamath PS. Survival in infection-related acuteon- chronic liver failure is defined by extrahepatic organ failures. Hepatology 2014; 60: 250-256 [PMID: 24677131 DOI: 10.1002/hep.27077]
60. Kotecha HL, Arora A, Chawlani R, Toshniwal J, Bansal N, Tyagi P, Sharma P, Kumar M, Kumar A. Low eosinophil count predicts inhospital mortality in cirrhosis with systemic inflammatory response syndrome. Eur J Gastroenterol Hepatol 2013; 25: 676-682 [PMID: 23411865 DOI: 10.1097/MEG.0b013e32835eb8f7]
61. Leithead JA, Rajoriya N, Gunson BK, Ferguson JW. Neutrophilto- lymphocyte ratio predicts mortality in patients listed for liver transplantation. Liver Int 2015; 35: 502-509 [PMID: 25234369 DOI: 10.1111/liv.12688]
62. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340: 448-454 [PMID: 9971870 DOI: 10.1056/nejm199902113400607]
63. Rahimkhani M, Einollahi N, Khavari Daneshvar H, Dashti N. Survey of serum procalcitonin in cirrhotic patients. Acta Med Iran 2013; 51: 153-156 [PMID: 23605598]
64. Lazzarotto C, Ronsoni MF, Fayad L, Nogueira CL, Bazzo ML, Narciso-Schiavon JL, de Lucca Schiavon L, Dantas-Corrêa EB. Acute phase proteins for the diagnosis of bacterial infection and prediction of mortality in acute complications of cirrhosis. Ann Hepatol 2013; 12: 599-607 [PMID: 23813138]
65. Huang WP, Jiang WQ, Hu B, Ye H, Zeng HK. [Significance of serum procalcitonin levels in the evaluation of severity and prognosis of patients with systemic inflammatory response syndrome]. Zhongguo Weizhongbing Jijiu Yixue 2012; 24: 294-297 [PMID: 22587926]
66. Cervoni JP, Thévenot T, Weil D, Muel E, Barbot O, Sheppard F, Monnet E, Di Martino V. C-reactive protein predicts short-term mortality in patients with cirrhosis. J Hepatol 2012; 56: 1299-1304 [PMID: 22314431 DOI: 10.1016/j.jhep.2011.12.030]
67. Di Martino V, Coutris C, Cervoni JP, Dritsas S, Weil D, Richou C, Vanlemmens C, Thevenot T. Prognostic value of C-reactive protein levels in patients with cirrhosis. Liver Transpl 2015; 21: 753-760 [PMID: 25677965 DOI: 10.1002/lt.24088]
68. Ruf AE, Villamil FG. C-reactive protein and model for end-stage liver disease score: Have we found the fifth element? Liver Transpl 2015; 21: 713-715 [PMID: 25846032 DOI: 10.1002/lt.24140]
69. Oh BS, Jang JW, Kwon JH, You CR, Chung KW, Kay CS, Jung HS, Lee S. Prognostic value of C-reactive protein and neutrophil-to-lymphocyte ratio in patients with hepatocellular carcinoma. BMC Cancer 2013; 13: 78 [PMID: 23409924 DOI: 10.1186/1471-2407-13-78]
70. Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, Fushiya N, Koike K, Nishino H, Matsushima M. The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma. Ann Surg Oncol 2015; 22: 803-810 [PMID: 25190127 DOI: 10.1245/s10434-014-4048-0]
71. Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, Fushiya N, Koike K, Nishino H, Matsushima M, Tajiri H. The addition of C-reactive protein to validated staging systems improves their prognostic ability in patients with hepatocellular carcinoma. Oncology 2014; 86: 308-317 [PMID: 24924697 DOI: 10.1159/000360704]