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Prediction of Complications of Cirrhosis: Molecular Biomarkers

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Abstract

The adequate stratification of patients with cirrhosis with clinical and molecular predictors of the development of cirrhosis-associated complications is fundamental in order to improve patient management and prognosis. A number of studies have attempted to identify clinical and molecular markers that accurately stage liver cirrhosis and help detect clinical complications. Currently, there are no commercially available molecular biomarkers that can be used in clinical practice. In most cases, molecular biomarkers reflect the existence of a complication, but their value for predictive assessment of complications is limited or has not been specifically evaluated. In this chapter, we review the existing knowledge on molecular markers for portal hypertension, ascites, and variceal bleeding; bacterial translocation and infections; hepatorenal syndrome (HRS) and acute kidney injury (AKI); and hepatic encephalopathy (HE).

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References

  1. Albilllos A, Garcia-Tsao G. Classification of cirrhosis: the clinical use of HVPG measurements. Dis Markers. 2011;31:121–28.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Martell M, Coll M, Ezkurdia N, Raurell I, Genescià J. Physiopathology of splanchnic vasodilation in portal hypertension. World J Hepatol. 2010;2:208–20.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Ripoll C, Groszmann R, Garcia-Tsao G, et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133:481–88.

    Article  CAS  PubMed  Google Scholar 

  4. Zein CO, Lindor KD, Angulo P. Prevalence and predictors of esophageal varices in patients with primary sclerosing cholangitis. Hepatology. 2004;39:204–10.

    Article  PubMed  Google Scholar 

  5. Castéra L, Le Bail B, Roudot-Thoraval F, Bernard P-H, Foucher J, Merrouche W, Couzigou P, de Lédinghen V. Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: comparison of transient elastography (FibroScan) with standard laboratory tests and non-invasive scores. J Hepatol. 2009;50:59–68.

    Article  PubMed  Google Scholar 

  6. Ghany MG, Lok ASF, Everhart JE, et al. Predicting clinical and histologic outcomes based on standard laboratory tests in advanced chronic hepatitis C. Gastroenterology. 2010;138:136–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, García-Pagán JC, Pinzani M, Bosch J. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology. 2013;44:102–11.e1.

    Article  Google Scholar 

  8. Lisotti A, Azzaroli F, Buonfiglioli F, et al. Indocyanine green retention test as a noninvasive marker of portal hypertension and esophageal varices in compensated liver cirrhosis. Hepatology. 2014;59:643–50.

    Article  CAS  PubMed  Google Scholar 

  9. Poynard T, Morra R, Halfon P, et al. Meta-analyses of FibroTest diagnostic value in chronic liver disease. BMC Gastroenterol. 2007;7:40.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Poynard T, Vergniol J, Ngo Y, et al. Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTestTM) and transient elastography (FibroScan®). J Hepatol. 2014;60:706–14.

    Article  PubMed  Google Scholar 

  11. Thabut D, Moreau R, Lebrec D. Noninvasive assessment of portal hypertension in patients with cirrhosis. Hepatology. 2011;53:683–94.

    Article  PubMed  Google Scholar 

  12. Thabut D, Imbert-Bismut F, Cazals-Hatem D, Messous D, Muntenau M, Valla DC, Moreau R, Poynard T, Lebrec D. Relationship between the Fibrotest and portal hypertension in patients with liver disease. Aliment Pharmacol Ther. 2007;26:359–68.

    Article  CAS  PubMed  Google Scholar 

  13. Fontana RJ, Sanyal AJ, Ghany MG, et al. Factors that determine the development and progression of gastroesophageal varices in patients with chronic hepatitis C. Gastroenterology. 2010;138:2321–31, 2331.e1–2.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Körner T, Kropf J, Gressner AM. Serum laminin and hyaluronan in liver cirrhosis: markers of progression with high prognostic value. J Hepatol. 1996;25:684–8.

    Article  PubMed  Google Scholar 

  15. Vanbiervliet G, Barjoan-Mariné E, Anty R, Piche T, Hastier P, Rakotoarisoa C, Benzaken S, Rampal P, Tran A. Serum fibrosis markers can detect large oesophageal varices with a high accuracy. Eur J Gastroenterol Hepatol. 2005;17:333–8.

    Article  PubMed  Google Scholar 

  16. La Mura V, Reverter JC, Flores-Arroyo A, Raffa S, Reverter E, Seijo S, Abraldes JG, Bosch J, García-Pagán JC. Von Willebrand factor levels predict clinical outcome in patients with cirrhosis and portal hypertension. Gut. 2011;60:1133–38.

    Article  CAS  PubMed  Google Scholar 

  17. Reiberger T, Ferlitsch A, Payer BA, Mandorfer M, Heinisch BB, Hayden H, Lammert F, Trauner M, Peck-Radosavljevic M, Vogelsang H. Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis. J Hepatol. 2013;58:911–21.

    Article  CAS  PubMed  Google Scholar 

  18. Buck M, Garcia-Tsao G, Groszmann RJ, Stalling C, Grace ND, Burroughs AK, Patch D, Matloff DS, Clopton P, Chojkier M. Novel inflammatory biomarkers of portal pressure in compensated cirrhosis patients. Hepatology. 2014;59:1052–9.

    Article  CAS  PubMed  Google Scholar 

  19. Holland-Fischer P, Grønbæk H, Sandahl TD, Moestrup SK, Riggio O, Ridola L, Aagaard NK, Møller HJ, Vilstrup H (2011) Kupffer cells are activated in cirrhotic portal hypertension and not normalised by TIPS. Gut. 60:1389–93.

    Google Scholar 

  20. Waidmann O, Brunner F, Herrmann E, Zeuzem S, Piiper A, Kronenberger B. Macrophage activation is a prognostic parameter for variceal bleeding and overall survival in patients with liver cirrhosis. J Hepatol. 2013;58:956–61

    Article  PubMed  Google Scholar 

  21. Grønbaek H, Sandahl TD, Mortensen C, Vilstrup H, Møller HJ, Møller S. Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis. Aliment Pharmacol Ther. 2012;36:173–80.

    Article  PubMed  Google Scholar 

  22. Zuckerman E, Lanir A, Sabo E, Rosenvald-Zuckerman T, Matter I, Yeshurun D, Eldar S. Cancer antigen 125: a sensitive marker of ascites in patients with liver cirrhosis. Am J Gastroenterol. 1999;94:1613–8.

    Article  CAS  PubMed  Google Scholar 

  23. Jalan R, Fernandez J, Wiest R, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol. 2014;60:1310–24.

    Article  PubMed  Google Scholar 

  24. 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;46:1872–82.

    Article  PubMed  Google Scholar 

  25. 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;51:475–82.

    Article  PubMed  Google Scholar 

  26. Leithead JA, Ferguson JW, Bates CM, Davidson JS, Lee A, Bathgate AJ, Hayes PC, Simpson KJ. The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure. Gut. 2009;58:443–9.

    Article  CAS  PubMed  Google Scholar 

  27. Fernández J, Gustot T. Management of bacterial infections in cirrhosis. J Hepatol. 2012;56(Suppl 1):S1–12.

    Article  PubMed  Google Scholar 

  28. Bellot P, Francés R, Such J. Pathological bacterial translocation in cirrhosis: pathophysiology, diagnosis and clinical implications. Liver Int. 2013;33:31–9.

    Article  CAS  PubMed  Google Scholar 

  29. Zapater P, Francés R, González-Navajas JM, et al. Serum and ascitic fluid bacterial DNA: a new independent prognostic factor in noninfected patients with cirrhosis. Hepatology. 2008;48:1924–31.

    Article  CAS  PubMed  Google Scholar 

  30. Appenrodt B, Lehmann LE, Thyssen L, Gentemann M, Rabe C, Molitor E, Trebicka J, Stüber F, Sauerbruch T. Is detection of bacterial DNA in ascitic fluid of clinical relevance? Eur J Gastroenterol Hepatol. 2010;22:1487–94.

    Article  CAS  PubMed  Google Scholar 

  31. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54.

    Article  CAS  PubMed  Google Scholar 

  32. Cervoni J-P, 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;56:1299–304.

    Article  CAS  PubMed  Google Scholar 

  33. Mortensen C, Andersen O, Krag A, Bendtsen F, Møller S. High-sensitivity C-reactive protein levels predict survival and are related to haemodynamics in alcoholic cirrhosis. Eur J Gastroenterol Hepatol. 2012;24:619–26.

    Article  CAS  PubMed  Google Scholar 

  34. Albillos A, de-la-Hera A, Alvarez-Mon M. Serum lipopolysaccharide-binding protein prediction of severe bacterial infection in cirrhotic patients with ascites. Lancet. 2004;363:1608–10.

    Article  CAS  PubMed  Google Scholar 

  35. Albillos A, de la Hera A, González M, Moya J-L, Calleja J-L, Monserrat J, Ruiz-del-Arbol L, Alvarez-Mon M. Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology. 2003;37:208–17.

    Article  CAS  PubMed  Google Scholar 

  36. 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.

    PubMed  Google Scholar 

  37. Papp M, Vitalis Z, Altorjay I, Tornai I, Udvardy M, Harsfalvi J, Vida A, Kappelmayer J, Lakatos PL, Antal-Szalmas P. Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infections. Liver Int. 2012;32:603–11.

    Article  CAS  PubMed  Google Scholar 

  38. Tsiakalos A, Karatzaferis A, Ziakas P, Hatzis G. Acute-phase proteins as indicators of bacterial infection in patients with cirrhosis. Liver Int. 2009;29:1538–42.

    Article  CAS  PubMed  Google Scholar 

  39. Byl B, Roucloux I, Crusiaux A, Dupont E, Devière J. Tumor necrosis factor alpha and interleukin 6 plasma levels in infected cirrhotic patients. Gastroenterology. 1993;104:1492–7.

    CAS  PubMed  Google Scholar 

  40. Martínez-Brú C, Gómez C, Cortés M, Soriano G, Guarner C, Planella T, González-Sastre F Ascitic fluid interleukin-8 to distinguish spontaneous bacterial peritonitis and sterile ascites in cirrhotic patients. Clin Chem. 1999;45:2027–8.

    PubMed  Google Scholar 

  41. Berres M-L, Schnyder B, Yagmur E, Inglis B, Stanzel S, Tischendorf JJW, Koch A, Winograd R, Trautwein C, Wasmuth HE. Longitudinal monocyte human leukocyte antigen-DR expression is a prognostic marker in critically ill patients with decompensated liver cirrhosis. Liver Int. 2009;29:536–43.

    Article  CAS  PubMed  Google Scholar 

  42. Kim JK, Chon CY, Kim JH, Kim YJ, Cho JH, Bang SM, Ahn SH, Han K-H, Moon YM. Changes in serum and ascitic monocyte chemotactic protein-1 (MCP-1) and IL-10 levels in cirrhotic patients with spontaneous bacterial peritonitis. J Interferon Cytokine Res. 2007;27:227–30.

    Article  CAS  PubMed  Google Scholar 

  43. Belcher JM, Sanyal AJ, Peixoto AJ, Perazella MA, Lim J, Thiessen-Philbrook H, Ansari N, Coca SG, Garcia-Tsao G., Parikh CR. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology. 2014;60:622–32.

    Google Scholar 

  44. Belcher JM, Parikh CR, Garcia-Tsao G. Acute kidney injury in patients with cirrhosis: perils and promise. Clin Gastroenterol Hepatol. 2013;11:1550–8.

    Article  CAS  PubMed  Google Scholar 

  45. Urbschat A, Obermüller N, Haferkamp A. Biomarkers of kidney injury. Biomarkers. 2011;16(Suppl 1):S22–30.

    Article  CAS  PubMed  Google Scholar 

  46. Barreto R, Guevara M. Biomarkers of acute kidney injury: a  trending topic  in cirrhosis. Gastroenterol Hepatol. 2013;36:407–421.

    Article  PubMed  Google Scholar 

  47. Fagundes C, Pépin M-N, Guevara M, et al. Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis. J Hepatol. 2012;57:267–73.

    Article  CAS  PubMed  Google Scholar 

  48. Verna EC, Brown RS, Farrand E, et al. Urinary neutrophil gelatinase-associated lipocalin predicts mortality and identifies acute kidney injury in cirrhosis. Dig Dis Sci. 2012;57:2362–70.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Barreto R, Fagundes C, Guevara M, et al. Type-1 hepatorenal syndrome associated with infections in cirrhosis: natural history, outcome of kidney function, and survival. Hepatology. 2014;59:1505–13.

    Article  PubMed  Google Scholar 

  50. Fagundes C, Barreto R, Guevara M, et al. A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis. J Hepatol. 2013;59:474–81.

    Article  PubMed  Google Scholar 

  51. Odutayo A, Cherney D. Cystatin C and acute changes in glomerular filtration rate. Clin Nephrol. 2012;78:64–75.

    Article  CAS  PubMed  Google Scholar 

  52. Sharawey MA, Shawky EM, Ali LH, Mohammed AA, Hassan HA, Fouad YM. Cystatin C: a predictor of hepatorenal syndrome in patients with liver cirrhosis. Hepatol Int. 2011;doi: 10.1007/s12072-011-9266-y.

    Google Scholar 

  53. Belcher JM, Sanyal AJ, Peixoto AJ, Perazella MA, Lim J, Thiessen-Philbrook H, Ansari N, Coca SG, Garcia-Tsao G, Parikh CR. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology. 2013;doi: 10.1002/hep.26980.

    Google Scholar 

  54. Rose CF. Ammonia-lowering strategies for the treatment of hepatic encephalopathy. Clin Pharmacol Ther. 2012;92:321–31.

    Article  CAS  PubMed  Google Scholar 

  55. Ong JP, Aggarwal A, Krieger D, Easley KA, Karafa MT, Van Lente F, Arroliga AC, Mullen KD (2003) Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 114:188–93.

    Google Scholar 

  56. Kundra A, Jain A, Banga A, Bajaj G, Kar P. Evaluation of plasma ammonia levels in patients with acute liver failure and chronic liver disease and its correlation with the severity of hepatic encephalopathy and clinical features of raised intracranial tension. Clin Biochem. 2005;38:696–9.

    Article  CAS  PubMed  Google Scholar 

  57. Bosoi CR, Rose CF. Identifying the direct effects of ammonia on the brain. Metab Brain Dis. 2009;24:95–102.

    Article  CAS  PubMed  Google Scholar 

  58. Stewart CA, Smith GE. Minimal hepatic encephalopathy. Nat Clin Pract Gastroenterol Hepatol. 2007;4:677–85.

    Article  PubMed  Google Scholar 

  59. Montoliu C, Cauli O, Urios A, et al. 3-nitro-tyrosine as a peripheral biomarker of minimal hepatic encephalopathy in patients with liver cirrhosis. Am J Gastroenterol. 2011;106:1629–37.

    Article  CAS  PubMed  Google Scholar 

  60. Shawcross DL, Davies NA, Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol. 2004;40:247–54.

    Article  CAS  PubMed  Google Scholar 

  61. Jain L, Sharma BC, Sharma P, Srivastava S, Agrawal A, Sarin SK. Serum endotoxin and inflammatory mediators in patients with cirrhosis and hepatic encephalopathy. Dig Liver Dis. 2012;44:1027–31

    Article  CAS  PubMed  Google Scholar 

  62. Montoliu C, Piedrafita B, Serra MA, Olmo JA, Urios A, Rodrigo JM. IL-6 and IL-18 in blood may discriminate cirrhotic encephalopathy. J Clin Gastroenterol. 2009;43:272–9.

    Article  CAS  PubMed  Google Scholar 

  63. Odeh M, Sabo E, Srugo I, Oliven A. Serum levels of tumor necrosis factor-alpha correlate with severity of hepatic encephalopathy due to chronic liver failure. Liver Int. 2004;24:110–6.

    Article  CAS  PubMed  Google Scholar 

  64. Alonso J, Córdoba J, Rovira A. Brain magnetic resonance in hepatic encephalopathy. Semin Ultrasound CT MR. 2014;35:136–52.

    Article  PubMed  Google Scholar 

  65. Chavarria L, Alonso J, García-Martínez R, Simón-Talero M, Ventura-Cots M, Ramírez C, Torrens M, Vargas V, Rovira A, Córdoba J. Brain magnetic resonance spectroscopy in episodic hepatic encephalopathy. J Cereb Blood Flow Metab. 2013;33:272–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institut d’Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Centre Esther Koplowitz, C/ Roselló, 149-153, third floor, 08036, Barcelona, Spain

    Mar Coll & Pau Sancho-Bru PhD

  2. Liver Unit, Hospital Clínic, University of Barcelona School of Medicine, Barcelona, Spain

    Elsa Solà

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  1. Mar Coll
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  2. Elsa Solà
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Correspondence to Pau Sancho-Bru PhD .

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Editors and Affiliations

  1. Department of Transplant, Mayo Clinic, Jacksonville, Florida, USA

    Andrew P. Keaveny

  2. Institut de Malalties Digestives i Metaboliques, University of Barcelona, Barcelona, Spain

    Andrés Cárdenas

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Coll, M., Solà, E., Sancho-Bru, P. (2015). Prediction of Complications of Cirrhosis: Molecular Biomarkers. In: Keaveny, A., Cárdenas, A. (eds) Complications of Cirrhosis. Springer, Cham. https://doi.org/10.1007/978-3-319-13614-1_3

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  • DOI: https://doi.org/10.1007/978-3-319-13614-1_3

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