Cirrhosis and Portal Hypertension: Staging and Prognosis

Chapter

Abstract

Cirrhosis is a dynamic and potentially reversible disease that progresses across different stages that are not only of prognostic significance but that have distinct predominant pathophysiological mechanisms that would, in many cases, necessitate different therapies. The compensated and decompensated stages are the most important stages and it is essential that they be analyzed, described and treated separately both clinically and in research studies. Within the compensated stage, the presence or absence of clinically significant portal hypertension (defined as an hepatic venous pressure gradient of 10 mmHg or higher) is a key determinant in the development of gastroesophageal varices and decompensation. In patients with clinically significant portal hypertension, the absence or presence of varices is a stratifying factor. Within the decompensated stage (defined by the presence of clinically overt complications (ascites, variceal hemorrhage and hepatic encephalopathy), the type and quantity of decompensating events adds to the prognostic granularity of the stage. A stage of “further” or late decompensation (defined by the development of refractory ascites, hepatorenal syndrome, recurrent variceal hemorrhage and recurrent/persistent hepatic encephalopathy) is likely to provide a larger prognostic differential among patients with decompensated cirrhosis. A final stage characterized by multi-organ failure, termed “acute-on-chronic” liver failure, is associated with the worst prognosis.

References

  1. 1.
    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;44:217–31.CrossRefPubMedGoogle Scholar
  2. 2.
    Ripoll C, Bari K, Garcia-Tsao G. Serum albumin can identify patients with compensated cirrhosis with a good prognosis. J Clin Gastroenterol. 2015;49:613–9.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Rosselli M, MacNaughtan J, Jalan R, Pinzani M. Beyond scoring: a modern interpretation of disease progression in chronic liver disease. Gut. 2013;62(9):1234–41.CrossRefPubMedGoogle Scholar
  4. 4.
    Bosch J, Groszmann RJ, Shah VH. Evolution in the understanding of the pathophysiological basis of portal hypertension: how changes in paradigm are leading to successful new treatments. J Hepatol. 2015;62(1S):S121–30.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bernardi M, Moreau R, Angeli P, Schnabl B, Arroyo V. Mechanisms of decompensation and organ failure in cirrhosis: from peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol. 2015;63(5):1272–84.CrossRefPubMedGoogle Scholar
  6. 6.
    D’Amico G, Pasta L, Morabito A, D’Amico M, Caltagirone M, Malizia G, et al. Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther. 2014;39(10):1180–93.CrossRefPubMedGoogle Scholar
  7. 7.
    de Franchis R, Baveno VI Faculty. Expanding consensus in portal hypertension. Report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743–52.CrossRefPubMedGoogle Scholar
  8. 8.
    Perello A, Escorsell A, Bru C, Gilabert R, Moitinho E, Garcia-Pagan JC, et al. Wedged hepatic venous pressure adequately reflects portal pressure in hepatitis C virus-related cirrhosis. Hepatology. 1999;30:1393–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Groszmann RJ, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Planas R, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med. 2005;353:2254–61.CrossRefPubMedGoogle Scholar
  10. 10.
    Ripoll C, Groszmann R, Garcia-Tsao G, Grace N, Burroughs A, Planas R, et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133(2):481–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Ripoll C, Groszmann RJ, Garcia-Tsao G, Bosch J, Grace N, Burroughs A, et al. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis. J Hepatol. 2009;50(5):923–8.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Garcia-Tsao G, Abraldes J, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis and management – 2016 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2017;65(1):310–35.CrossRefPubMedGoogle Scholar
  13. 13.
    Nagula S, Jain D, Groszmann RJ, Garcia-Tsao G. Histological-hemodynamic correlation in cirrhosis—a histological classification of the severity of cirrhosis. J Hepatol. 2006;44(1):111–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Kumar M, Sakhuja P, Kumar A, Manglik N, Choudhury A, Hissar S, et al. Histological subclassification of cirrhosis based on histological-haemodynamic correlation. Aliment Pharmacol Ther. 2008;27(9):771–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Sethasine S, Jain D, Groszmann RJ, Garcia-Tsao G. Quantitative histological-hemodynamic correlations in cirrhosis. Hepatology. 2012;55(4):1146–53.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Villanueva C, Albillos A, Genesca J, Abraldes JG, Calleja JL, Aracil C, et al. Development of hyperdynamic circulation and response to beta-blockers in compensated cirrhosis with portal hypertension. Hepatology. 2016;63(1):197–206.CrossRefPubMedGoogle Scholar
  17. 17.
    Mandorfer M, Kozbial K, Schwabl P, Freissmuth C, Schwarzer R, Stern R, et al. Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension. J Hepatol. 2016;65(4):692–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Bruno S, Zuin M, Crosignani A, Rossi S, Zadra F, Roffi L, et al. Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study. Am J Gastroenterol. 2009;104(5):1147–58.CrossRefPubMedGoogle Scholar
  19. 19.
    Zipprich A, Garcia-Tsao G, Rogowski S, Fleig WE, Seufferlein T, Dollinger MM. Prognostic indicators of survival in patients with compensated and decompensated cirrhosis. Liver Int. 2012;32(9):1407–14.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Lebrec D, De Fleury P, Rueff B, Nahum H, Benhamou JP. Portal hypertension, size of esophageal varices, and risk of gastrointestinal bleeding in alcoholic cirrhosis. Gastroenterology. 1980;79:1139–44.PubMedGoogle Scholar
  21. 21.
    Garcia-Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickman M. Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology. 1985;5(3):419–24.CrossRefPubMedGoogle Scholar
  22. 22.
    Villanueva C, et al. . β-Blockers to prevent the decompensation of cirrhosis in patients with clinically significant portal hypertension. AASLD 2016 abstract.Google Scholar
  23. 23.
    Poynard T, Cales P, Pasta L, Ideo G, Pascal JP, Pagliaro L, et al. Beta-adrenergic antagonists in the prevention of first gastrointestinal bleeding in patients with cirrhosis and oesophageal varices. An analysis of data and prognostic factors in 598 patients from four randomized clinical trials. N Engl J Med. 1991;324:1532–8.CrossRefPubMedGoogle Scholar
  24. 24.
    D’Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis. 1999;19:475–505.CrossRefPubMedGoogle Scholar
  25. 25.
    Villanueva C, Aracil C, Colomo A, Hernandez-Gea V, Lopez-Balaguer JM, Alvarez-Urturi C, et al. Acute hemodynamic response to beta-blockers and prediction of long-term outcome in primary prophylaxis of variceal bleeding. Gastroenterology. 2009;137(1):119–28.CrossRefPubMedGoogle Scholar
  26. 26.
    Hernandez-Gea V, Aracil C, Colomo A, Garupera I, Poca M, Torras X, et al. Development of ascites in compensated cirrhosis with severe portal hypertension treated with beta-blockers. Am J Gastroenterol. 2012;107(3):418–27.CrossRefPubMedGoogle Scholar
  27. 27.
    Turco L, et al. A reduction in the hepatic venous pressure gradient (HVPG) prevents clinical outcomes in compensated and decompensated cirrhosis: A meta-analysis. EASL 2017 abstract.Google Scholar
  28. 28.
    Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology. 2006;43(2 Suppl 1):S121–31.CrossRefPubMedGoogle Scholar
  29. 29.
    Bruno S, Saibeni S, Bagnardi V, Vandelli C, De LM, Felder M, et al. Mortality risk according to different clinical characteristics of first episode of liver decompensation in cirrhotic patients: a nationwide, prospective, 3-year follow-up study in Italy. Am J Gastroenterol. 2013;108(7):1112–22.CrossRefPubMedGoogle Scholar
  30. 30.
    Moitinho E, Escorsell A, Bandi JC, Salmeron JM, Garcia-Pagan JC, Rodes J, et al. Prognostic value of early measurements of portal pressure in acute variceal bleeding. Gastroenterology. 1999;117:626–31.CrossRefPubMedGoogle Scholar
  31. 31.
    Abraldes JG, Villanueva C, Banares R, Aracil C, Catalina MV, Garci A-P, et al. Hepatic venous pressure gradient and prognosis in patients with acute variceal bleeding treated with pharmacologic and endoscopic therapy. J Hepatol. 2008;48(2):229–36.CrossRefPubMedGoogle Scholar
  32. 32.
    Abraldes JG, Albillos A, Banares R, Turnes J, Gonzalez R, Garcia-Pagan JC, et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009;136(5):1651–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Abraldes JG, Villanueva C, Aracil C, Turnes J, Hernandez-Guerra M, Genesca J, et al. Addition of simvastatin to standard therapy for the prevention of variceal rebleeding does not reduce rebleeding but increases survival in patients with cirrhosis. Gastroenterology. 2016;150(5):1160–70.CrossRefPubMedGoogle Scholar
  34. 34.
    Garcia-Pagan JC, Di PM, Caca K, Laleman W, Bureau C, Appenrodt B, 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.CrossRefPubMedGoogle Scholar
  35. 35.
    Laleman W, Simon-Talero M, Maleux G, Perez M, Ameloot K, Soriano G, et al. Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy. Hepatology. 2013;57(6):2448–57.CrossRefPubMedGoogle Scholar
  36. 36.
    Albillos A, Zamora J, Martinez J, Arroyo D, Ahmad I, de la Pena J, et al. Stratifying risk in the prevention of recurrent variceal hemorrhage: results of an individual patient meta-analysis. Hepatology. 2017;66(4):1219–31.CrossRefPubMedGoogle Scholar
  37. 37.
    Salerno F, Borroni G, Moser P, Badalamenti S, Cassara L, Maggi M, et al. Survival and prognostic factors of cirrhotic patients with ascites: a study of 134 outpatients. Am J Gastroenterol. 1993;88:514–9.PubMedGoogle Scholar
  38. 38.
    Kim WR, Biggins SW, Kremers WK, Wiesner RH, Kamath PS, Benson JT, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med. 2008;359(10):1018–26.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Alessandria C, Ozdogan O, Guevara M, Restuccia T, Jimenez W, Arroyo V, et al. MELD score and clinical type predict prognosis in hepatorenal syndrome: relevance to liver transplantation. Hepatology. 2005;41(6):1282–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48(6):2064–77.CrossRefPubMedGoogle Scholar
  41. 41.
    Abraldes JG, Aracil C, Catalina MV, Monescillo A, Banares R, Villanueva C, et al. Value of HVPG predicting 5-day treatment failure in acute variceal bleeding. Comparison with clinical variables. J Hepatol. 2006;44(Suppl 2):S12. (abstract)CrossRefGoogle Scholar
  42. 42.
    Wiest R, Das S, Cadelina G, Garcia-Tsao G, Milstien S, Groszmann RJ. Bacterial translocation to lymph nodes of cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility. J Clin Invest. 1999;104:1223–33.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodes J. Peripheral arterial vasodilation hypothesis – a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8:1151–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Fernandez J, Navasa M, Planas R, Montoliu S, Monfort D, Soriano G, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133(3):818–24.CrossRefPubMedGoogle Scholar
  45. 45.
    Villa E, Camma C, Marietta M, Luongo M, Critelli R, Colopi S, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology. 2012;143(5):1253–60.CrossRefPubMedGoogle Scholar
  46. 46.
    Gluud LL, Christensen K, Christensen E, Krag A. Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome. Hepatology. 2010;51:576–84.CrossRefPubMedGoogle Scholar
  47. 47.
    Bureau C, Thabut D, Oberti F, Dharancy S, Carbonell N, Bouvier A, et al. Transjugular intrahepatic portosystemic shunts with covered stents increase transplant-free survival of patients with cirrhosis and recurrent ascites. Gastroenterology. 2017;152(1):157–63.CrossRefPubMedGoogle Scholar
  48. 48.
    Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144(7):1426–37.CrossRefPubMedGoogle Scholar
  49. 49.
    Bajaj JS, O’Leary JG, Reddy KR, Wong F, Biggins SW, Patton H, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology. 2014;60(1):250–6.  https://doi.org/10.1002/hep.27077.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Albillos A, Lario M, Alvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61(6):1385–96.CrossRefPubMedGoogle Scholar
  51. 51.
    Mookerjee RP, Pavesi M, Thomsen KL, Mehta G, MacNaughtan J, Bendtsen F, et al. Treatment with non-selective beta-blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure. J Hepatol. 2016;64(3):574–82. Epub 2015 Oct 28CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Section of Digestive DiseasesYale University School of MedicineNew HavenUSA
  2. 2.Digestive Diseases SectionVA-CT Healthcare SystemWest HavenUSA

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