Semin Liver Dis 2016; 36(02): 167-173
DOI: 10.1055/s-0036-1583195
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Predisposing Factors in Acute-on-Chronic Liver Failure

Jonel Trebicka
1   Department of Internal Medicine I, University of Bonn, Bonn, Germany
2   Department of Gastroenterology and Hepatology, University of Southern Denmark, Odense, Denmark
› Author Affiliations
Further Information

Publication History

Publication Date:
12 May 2016 (online)

Abstract

Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality in patients with chronic liver disease. The definition of ACLF has been addressed recently in many publications, and despite regional differences the number and severity of organ failures are decisive for the presence and severity of ACLF. However, the predisposition of patients to develop ACLF has not been addressed in prospective studies. Several predisposing factors for ACLF have been mentioned, but still clear-cut analysis and the sequential processes have not been explored. One reason is that different factors might predispose in one setting and might be the precipitating event in another, thus rendering the generalization of predisposing factors difficult. However, genetic factors, lifestyle, past medical history, aging, latent chronic infections, and the severity of the liver disease and portal hypertension might predispose for the development of ACLF after proper injury and response.

 
  • References

  • 1 Moreau R, Jalan R, Gines P , et al; CANONIC Study Investigators of the EASL–CLIF Consortium. Acute-on-chronic liver fa. tumor necrosis factor ure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013; 144 (7) 1426-1437 , 1437.e1–1437.e9
  • 2 Arroyo V, Moreau R, Jalan R, Ginès P ; EASL-CLIF Consortium CANONIC Study. Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis. J Hepatol 2015; 62 (1, Suppl): S131-S143
  • 3 Moreau R, Jalan R, Arroyo V. Acute-on-chronic liver failure: recent concepts. J Clin Exp Hepatol 2015; 5 (1) 81-85
  • 4 Sarin SK, Kedarisetty CK, Abbas Z , et al; APASL ACLF Working Party. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol Int 2014; 8 (4) 453-471
  • 5 Galbois A, Aegerter P, Martel-Samb P , et al; Collège des Utilisateurs des Bases des données en Réanimation (CUB-Réa) Group. Improved prognosis of septic shock in patients with cirrhosis: a multicenter study*. Crit Care Med 2014; 42 (7) 1666-1675
  • 6 Sauneuf B, Champigneulle B, Soummer A , et al. Increased survival of cirrhotic patients with septic shock. Crit Care 2013; 17 (2) R78
  • 7 Olson JC, Wendon JA, Kramer DJ , et al. Intensive care of the patient with cirrhosis. Hepatology 2011; 54 (5) 1864-1872
  • 8 Jalan R, Gines P, Olson JC , et al. Acute-on chronic liver failure. J Hepatol 2012; 57 (6) 1336-1348
  • 9 Jalan R, Stadlbauer V, Sen S, Cheshire L, Chang YM, Mookerjee RP. Role of predisposition, injury, response and organ failure in the prognosis of patients with acute-on-chronic liver failure: a prospective cohort study. Crit Care 2012; 16 (6) R227
  • 10 Rosselli M, MacNaughtan J, Jalan R, Pinzani M. Beyond scoring: a modern interpretation of disease progression in chronic liver disease. Gut 2013; 62 (9) 1234-1241
  • 11 Shi Y, Yang Y, Hu Y , et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 2015; 62 (1) 232-242
  • 12 Jalan R, Pavesi M, Saliba F , et al; CANONIC Study Investigators; EASL-CLIF Consortium. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol 2015; 62 (4) 831-840
  • 13 Gustot T, Fernandez J, Garcia E , et al; CANONIC Study Investigators of the EASL-CLIF Consortium. Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology 2015; 62 (1) 243-252
  • 14 Jalan R, Saliba F, Pavesi M , et al; CANONIC study investigators of the EASL-CLIF Consortium. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 2014; 61 (5) 1038-1047
  • 15 Bajaj JS, O'Leary JG, Reddy KR , et al; North American Consortium For The Study Of End-Stage Liver Disease Nacseld. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology 2014; 60 (1) 250-256
  • 16 O'Brien AJ, Fullerton JN, Massey KA , et al. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nat Med 2014; 20 (5) 518-523
  • 17 Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011; 53 (6) 1883-1894
  • 18 Speliotes EK, Yerges-Armstrong LM, Wu J , et al; NASH CRN; GIANT Consortium; MAGIC Investigators; GOLD Consortium. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 2011; 7 (3) e1001324
  • 19 Appenrodt B, Grünhage F, Gentemann MG, Thyssen L, Sauerbruch T, Lammert F. Nucleotide-binding oligomerization domain containing 2 (NOD2) variants are genetic risk factors for death and spontaneous bacterial peritonitis in liver cirrhosis. Hepatology 2010; 51 (4) 1327-1333
  • 20 Casper M, Mengel M, Fuhrmann C , et al; INCA trial group. The INCA trial (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites): study protocol for a randomized controlled trial. Trials 2015; 16: 83
  • 21 Derhovanessian E, Maier AB, Beck R , et al. Hallmark features of immunosenescence are absent in familial longevity. J Immunol 2010; 185 (8) 4618-4624
  • 22 Deleidi M, Jäggle M, Rubino G. Immune aging, dysmetabolism, and inflammation in neurological diseases. Front Neurosci 2015; 9: 172
  • 23 Romero-Gómez M, Jover M, Del Campo JA , et al. Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study. Ann Intern Med 2010; 153 (5) 281-288
  • 24 Mayer LB, Krawczyk M, Grünhage F, Lammert F, Stokes CS. A genetic variant in the promoter of phosphate-activated glutaminase is associated with hepatic encephalopathy. J Intern Med 2015; 278 (3) 313-322
  • 25 Zeybel M, Hardy T, Wong YK , et al. Multigenerational epigenetic adaptation of the hepatic wound-healing response. Nat Med 2012; 18 (9) 1369-1377
  • 26 Hrubec Z, Omenn GS. Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: twin concordances for alcoholism and its biological end points by zygosity among male veterans. Alcohol Clin Exp Res 1981; 5 (2) 207-215
  • 27 Stickel F, Buch S, Lau K , et al. Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians. Hepatology 2011; 53 (1) 86-95
  • 28 Tian C, Stokowski RP, Kershenobich D, Ballinger DG, Hinds DA. Variant in PNPLA3 is associated with alcoholic liver disease. Nat Genet 2010; 42 (1) 21-23
  • 29 Rao R. Endotoxemia and gut barrier dysfunction in alcoholic liver disease. Hepatology 2009; 50 (2) 638-644
  • 30 Trebicka J, Krag A, Gansweid S , et al. Endotoxin and tumor necrosis factor-receptor levels in portal and hepatic vein of patients with alcoholic liver cirrhosis receiving elective transjugular intrahepatic portosystemic shunt. Eur J Gastroenterol Hepatol 2011; 23 (12) 1218-1225
  • 31 Trebicka J, Krag A, Gansweid S , et al. Soluble TNF-alpha-receptors I are prognostic markers in TIPS-treated patients with cirrhosis and portal hypertension. PLoS ONE 2013; 8 (12) e83341
  • 32 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 (3) 724-734
  • 33 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 (2) 437-447
  • 34 Dubuquoy L, Louvet A, Lassailly G , et al. Progenitor cell expansion and impaired hepatocyte regeneration in explanted livers from alcoholic hepatitis. Gut 2015; 64 (12) 1949-1960
  • 35 Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update. Physiol Rev 2013; 93 (1) 359-404
  • 36 Raynard B, Balian A, Fallik D , et al. Risk factors of fibrosis in alcohol-induced liver disease. Hepatology 2002; 35 (3) 635-638
  • 37 Butt Z, Jadoon NA, Salaria ON , et al. Diabetes mellitus and decompensated cirrhosis: risk of hepatic encephalopathy in different age groups. J Diabetes 2013; 5 (4) 449-455
  • 38 Kalaitzakis E, Olsson R, Henfridsson P , et al. Malnutrition and diabetes mellitus are related to hepatic encephalopathy in patients with liver cirrhosis. Liver Int 2007; 27 (9) 1194-1201
  • 39 Ampuero J, Ranchal I, del Mar Díaz-Herrero M, del Campo JA, Bautista JD, Romero-Gómez M. Role of diabetes mellitus on hepatic encephalopathy. Metab Brain Dis 2013; 28 (2) 277-279
  • 40 Basu S, Zethelius B, Helmersson J, Berne C, Larsson A, Arnlöv J. Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men. Int J Clin Exp Med 2011; 4 (2) 164-168
  • 41 Sigal SH, Stanca CM, Kontorinis N, Bodian C, Ryan E. Diabetes mellitus is associated with hepatic encephalopathy in patients with HCV cirrhosis. Am J Gastroenterol 2006; 101 (7) 1490-1496
  • 42 Borhofen SM, Gerner C, Lehmann J , et al. The Royal Free Hospital-Nutritional Prioritizing Tool Is an Independent Predictor of Deterioration of Liver Function and Survival in Cirrhosis. Dig Dis Sci 2016;
  • 43 Mathurin P, Bataller R. Trends in the management and burden of alcoholic liver disease. J Hepatol 2015; 62 (1, Suppl): S38-S46
  • 44 Altamirano J, Miquel R, Katoonizadeh A , et al. A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology 2014; 146 (5) 1231-9.e1 , 6
  • 45 Naveau S, Giraud V, Borotto E, Aubert A, Capron F, Chaput JC. Excess weight risk factor for alcoholic liver disease. Hepatology 1997; 25 (1) 108-111
  • 46 Pérez-Carreras M, Del Hoyo P, Martín MA , et al. Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology 2003; 38 (4) 999-1007
  • 47 Koliaki C, Szendroedi J, Kaul K , et al. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab 2015; 21 (5) 739-746
  • 48 Trebicka J, Schierwagen R. Hepatic mitochondrial dysfunction in non-alcoholic steatohepatitis: read-out or reason?. Hepatology 2016;
  • 49 Shi Y, Zheng MH, Yang Y , et al. Increased delayed mortality in patients with acute-on-chronic liver failure who have prior decompensation. J Gastroenterol Hepatol 2015; 30 (4) 712-718
  • 50 Bajaj JS, O'Leary JG, Reddy KR , et al; NACSELD. Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American consortium for the study of end-stage liver disease (NACSELD) experience. Hepatology 2012; 56 (6) 2328-2335
  • 51 Asrani SK, O'Leary JG. Acute-on-chronic liver failure. Clin Liver Dis 2014; 18 (3) 561-574
  • 52 Bernard B, Cadranel JF, Valla D, Escolano S, Jarlier V, Opolon P. Prognostic significance of bacterial infection in bleeding cirrhotic patients: a prospective study. Gastroenterology 1995; 108 (6) 1828-1834
  • 53 Bajaj JS, Ratliff SM, Heuman DM, Lapane KL. Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis. Aliment Pharmacol Ther 2012; 36 (9) 866-874
  • 54 Garg H, Kumar A, Garg V, Sharma P, Sharma BC, Sarin SK. Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure. Dig Liver Dis 2012; 44 (2) 166-171
  • 55 Aspinall R, Del Giudice G, Effros RB, Grubeck-Loebenstein B, Sambhara S. Challenges for vaccination in the elderly. Immun Ageing 2007; 4: 9
  • 56 Gavazzi G, Krause KH. Ageing and infection. Lancet Infect Dis 2002; 2 (11) 659-666
  • 57 Franceschi C, Bonafè M, Valensin S , et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000; 908: 244-254
  • 58 Franceschi C, Capri M, Monti D , et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 2007; 128 (1) 92-105
  • 59 Goronzy JJ, Weyand CM. Understanding immunosenescence to improve responses to vaccines. Nat Immunol 2013; 14 (5) 428-436
  • 60 Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology 2008; 134 (6) 1655-1669
  • 61 Green DR, Galluzzi L, Kroemer G. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science 2011; 333 (6046) 1109-1112
  • 62 Koch S, Larbi A, Ozcelik D , et al. Cytomegalovirus infection: a driving force in human T cell immunosenescence. Ann N Y Acad Sci 2007; 1114: 23-35
  • 63 Gruener NH, Lechner F, Jung MC , et al. Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus. J Virol 2001; 75 (12) 5550-5558
  • 64 Nikolich-Zugich J. Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nat Rev Immunol 2008; 8 (7) 512-522
  • 65 Su LF, Kidd BA, Han A, Kotzin JJ, Davis MM. Virus-specific CD4(+) memory-phenotype T cells are abundant in unexposed adults. Immunity 2013; 38 (2) 373-383
  • 66 Maggio M, Basaria S, Ble A , et al. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. J Clin Endocrinol Metab 2006; 91 (1) 345-347
  • 67 Abu-Taha M, Rius C, Hermenegildo C , et al. Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losartan. J Immunol 2009; 183 (2) 1393-1402
  • 68 Derhovanessian E, Maier AB, Hähnel K , et al. Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of late-differentiated CD4+ and CD8+ T-cells in humans. J Gen Virol 2011; 92 (Pt 12) 2746-2756
  • 69 Mortensen LH, Maier AB, Slagbom PE , et al. Early-life environment influencing susceptibility to cytomegalovirus infection: evidence from the Leiden Longevity Study and the Longitudinal Study of Aging Danish Twins. Epidemiol Infect 2012; 140 (5) 835-841
  • 70 Beyer M, Abdullah Z, Chemnitz JM , et al. Tumor necrosis factor impairs CD4+ T cell-mediated immunological control in chronic viral infection. Nat Immunol 2016; ; Mar 7: [Epub ahead of print]
  • 71 Sun LJ, Yu JW, Zhao YH, Kang P, Li SC. Influential factors of prognosis in lamivudine treatment for patients with acute-on-chronic hepatitis B liver failure. J Gastroenterol Hepatol 2010; 25 (3) 583-590
  • 72 Wlodzimirow KA, Eslami S, Abu-Hanna A, Nieuwoudt M, Chamuleau RA. A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality. Liver Int 2013; 33 (1) 40-52
  • 73 Sargenti K, Prytz H, Nilsson E, Kalaitzakis E. Predictors of mortality among patients with compensated and decompensated liver cirrhosis: the role of bacterial infections and infection-related acute-on-chronic liver failure. Scand J Gastroenterol 2015; 50 (7) 875-883
  • 74 Sargenti K, Prytz H, Strand A, Nilsson E, Kalaitzakis E. Healthcare-associated and nosocomial bacterial infections in cirrhosis: predictors and impact on outcome. Liver Int 2015; 35 (2) 391-400
  • 75 Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver Int 2006; 26 (10) 1175-1186
  • 76 Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol 2014; 61 (6) 1385-1396
  • 77 Asrani SK, Simonetto DA, Kamath PS. Acute-on-Chronic Liver Failure. Clin Gastroenterol Hepatol 2015; 13 (12) 2128-2139
  • 78 Christou L, Pappas G, Falagas ME. Bacterial infection-related morbidity and mortality in cirrhosis. Am J Gastroenterol 2007; 102 (7) 1510-1517
  • 79 Wong F. Recent advances in our understanding of hepatorenal syndrome. Nat Rev Gastroenterol Hepatol 2012; 9 (7) 382-391
  • 80 Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet 2014; 383 (9930) 1749-1761
  • 81 Bosch J, Abraldes JG, Berzigotti A, García-Pagan JC. The clinical use of HVPG measurements in chronic liver disease. Nat Rev Gastroenterol Hepatol 2009; 6 (10) 573-582
  • 82 Ripoll C, Groszmann RJ, Garcia-Tsao G , et al; Portal Hypertension Collaborative Group. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis. J Hepatol 2009; 50 (5) 923-928
  • 83 Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology 2005; 41 (3) 422-433
  • 84 Berres ML, Asmacher S, Lehmann J , et al. CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt. J Hepatol 2015; 62 (2) 332-339
  • 85 Rabe C, Schmitz V, Paashaus M , et al. Does intubation really equal death in cirrhotic patients? Factors influencing outcome in patients with liver cirrhosis requiring mechanical ventilation. Intensive Care Med 2004; 30 (8) 1564-1571
  • 86 Mandorfer M, Bota S, Schwabl P , et al. Nonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology 2014; 146 (7) 1680-90.e1
  • 87 Garg H, Kumar A, Garg V , et al. Hepatic and systemic hemodynamic derangements predict early mortality and recovery in patients with acute-on-chronic liver failure. J Gastroenterol Hepatol 2013; 28 (8) 1361-1367
  • 88 García-Pagán JC, Caca K, Bureau C , et al; Early TIPS (Transjugular Intrahepatic Portosystemic Shunt) Cooperative Study Group. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 2010; 362 (25) 2370-2379
  • 89 Garcia-Pagán JC, Di Pascoli M, Caca K , et al. Use of early-TIPS for high-risk variceal bleeding: results of a post-RCT surveillance study. J Hepatol 2013; 58 (1) 45-50
  • 90 Berres ML, Lehmann J, Jansen C , et al. Chemokine (C-X-C motif) ligand 11 levels predict survival in cirrhotic patients with transjugular intrahepatic portosystemic shunt. Liver Int 2016; 36 (3) 386-394
  • 91 Arroyo V, Moreau R. Tying up PGE2 with albumin to relieve immunosuppression in cirrhosis. Nat Med 2014; 20 (5) 467-469
  • 92 Arroyo V, García-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol 2014; 61 (2) 396-407