Pathophysiological-based treatments of complications of cirrhosis

References

• Mokdad AA, Lopez AD, Shahraz S, et al. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Med. 2014;12(1):145.
   PubMed Web of Science ®Google Scholar
• Blachier M, Leleu H, Peck-Radosavljevic M, et al. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013;58(3):593–608.
   PubMed Web of Science ®Google Scholar
• Jepsen P, Lash TL, Vilstrup H. The clinical course of alcoholic cirrhosis: development of comorbid diseases. A Danish nationwide cohort study. Liver Int. 2016;36(11):1696–1703.
   PubMed Web of Science ®Google Scholar
• Allen AM, Kim WR, Moriarty JP, et al. Time trends in the Hhalthcare burden and mortality of acute on chronic liver failure (ACLF) in the United States. Hepatology. 2016;64(6):2165–2172.
   PubMed Web of Science ®Google Scholar
• Tandon P, Garcia-Tsao G. Bacterial infections, sepsis, and multiorgan failure in cirrhosis. Semin Liver Dis. 2008;28(1):026–042.
   PubMed Web of Science ®Google Scholar
• Møller S, Bendtsen F. Cirrhotic multiorgan syndrome. Dig Dis Sci. 2015;60(11):3209–3225.
   PubMed Web of Science ®Google Scholar
• Das UN. Beneficial role of bioactive lipids in the pathobiology, prevention, and management of HBV, HCV and alcoholic hepatitis, NAFLD, and liver cirrhosis: a review. J Adv Res. 2019;17:17–29.
   PubMed Web of Science ®Google Scholar
• Pimpin L, Cortez-Pinto H, Negro F, et al. Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies. J Hepatol. 2018;69(3):718–735.
   PubMed Web of Science ®Google Scholar
• Levy S, Samuel D. Prevention of decompensation in cirrhosis: a new youth for beta blockers. Lancet. 2019;393(10181):1571–1572.
   PubMed Web of Science ®Google Scholar
• Vilaseca M, Guixe-Muntet S, Fernandez-Iglesias A, et al. Advances in therapeutic options for portal hypertension. Therap Adv Gastroenterol. 2018;11:175628481881129.
   Web of Science ®Google Scholar
• Becker U, Deis A, Sorensen TIA, et al. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology. 1996;23(5):1025–1029.
   PubMed Web of Science ®Google Scholar
• Dam MK, Flensborg-Madsen T, Eliasen M, et al. Smoking and risk of liver cirrhosis: a population-based cohort study. Scand J Gastroenterol. 2013;48(5):585–591.
   PubMed Web of Science ®Google Scholar
• Dam-Larsen S, Franzmann MB, Christoffersen P, et al. Histological characteristics and prognosis in patients with fatty liver. Scand J Gastroenterol. 2005;40(4):460–467.
   PubMed Web of Science ®Google Scholar
• Stickel F, Datz C, Hampe J, et al. Pathophysiology and management of alcoholic liver disease: update 2016. Gut Liver. 2017;11(2):173–188.
   PubMed Web of Science ®Google Scholar
• Laursen TL, Hagemann CA, Wei C, et al. Bariatric surgery in patients with non-alcoholic fatty liver disease – from pathophysiology to clinical effects. WJH. 2019;11(2):138–149.
   PubMed Web of Science ®Google Scholar
• Friedman SL, Neuschwander-Tetri BA, Rinella M, et al. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24(7):908–922.
   PubMed Web of Science ®Google Scholar
• Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1):S47–S64.
   PubMed Web of Science ®Google Scholar
• Traussnigg S, Kienbacher C, Halilbasic E, et al. Challenges and management of liver cirrhosis: practical issues in the therapy of patients with cirrhosis due to NAFLD and NASH. Dig Dis. 2015;33(4):598–607.
   PubMed Web of Science ®Google Scholar
• Jahn D, Rau M, Wohlfahrt J, et al. Non-alcoholic steatohepatitis: from pathophysiology to novel therapies. Dig Dis. 2016;34(4):356–363.
   PubMed Web of Science ®Google Scholar
• Adams LA. End-points for drug treatment in NASH. Hepatol Int. 2019;13(3):253–258.
   PubMed Web of Science ®Google Scholar
• Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis – current status and future directions. J Hepatol. 2014;61(4):912–924.
   PubMed Web of Science ®Google Scholar
• Greuter T, Shah VH. Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights. J Gastroenterol. 2016;51(6):511–519.
   PubMed Web of Science ®Google Scholar
• Ames PR, Guardascione M, Batuca JR, et al. Nitric oxide metabolites, nitrative stress, and paraoxonase activity in hepatopulmonary syndrome. Scand J Gastroenterol. 2016;51(1):73–77.
   PubMed Web of Science ®Google Scholar
• Abraldes JG, Iwakiri Y, Loureiro-Silva M, et al. Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. Am J Physiol Gastrointest Liver Physiol. 2006;290(5):G980–G987.
   PubMed Web of Science ®Google Scholar
• Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008;88(1):125–172.
   PubMed Web of Science ®Google Scholar
• Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol. 2011;25(2):195–206.
   PubMed Web of Science ®Google Scholar
• Friedman SL, Sheppard D, Duffield JS, et al. Therapy for fibrotic diseases: nearing the starting line. Sci Transl Med. 2013;5(167):167sr1–167sr1.
   PubMed Web of Science ®Google Scholar
• Schuppan D, Surabattula R, Wang XY. Determinants of fibrosis progression and regression in NASH. J Hepatol. 2018;68(2):238–250.
   PubMed Web of Science ®Google Scholar
• Rockey DC. Hepatic fibrosis, stellate cells, and portal hypertension. Clin Liver Dis. 2006;10(3):459–479.
   PubMedGoogle Scholar
• Puche JE, Saiman Y, Friedman SL. Hepatic stellate cells and liver fibrosis. Compr Physiol. 2013;3(4):1473–1492.
   PubMed Web of Science ®Google Scholar
• DeLeve LD. Liver sinusoidal endothelial cells and liver regeneration. J Clin Invest. 2013;123(5):1861–1866.
   PubMed Web of Science ®Google Scholar
• Gracia-Sancho J, Marrone G, Fernández-Iglesias A. Hepatic microcirculation and mechanisms of portal hypertension. Nat Rev Gastroenterol Hepatol. 2019;16(4):221–234.
   PubMed Web of Science ®Google Scholar
• Hammoutene A, Rautou PE. Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. J Hepatol. 2019;70(6):1278–1291.
   PubMed Web of Science ®Google Scholar
• Braet F, Wisse E. Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review. Comp Hepatol. 2002;1(1):1.
   PubMedGoogle Scholar
• Iwakiri Y, Kim MY. Nitric oxide in liver diseases. Trends Pharmacol Sci. 2015;36(8):524–536.
   PubMed Web of Science ®Google Scholar
• Banales JM, Marzioni M, Larusso NF, et al. Cholangiocytes in health and disease: from basic science to novel treatments. Biochim Biophys Acta Mol Basis Dis. 2018;1864(4):1217–1219.
   PubMed Web of Science ®Google Scholar
• Luo B, Tang L, Wang Z, et al. Cholangiocyte endothelin 1 and transforming growth factor beta1 production in rat experimental hepatopulmonary syndrome. Gastroenterology. 2005;129(2):682–695.
   PubMed Web of Science ®Google Scholar
• Lukacs-Kornek V, Lammert F. The progenitor cell dilemma: cellular and functional heterogeneity in assistance or escalation of liver injury. J Hepatol. 2017;66(3):619–630.
   PubMed Web of Science ®Google Scholar
• Lleo A, Maroni L, Glaser S, et al. Role of cholangiocytes in primary biliary cirrhosis. Semin Liver Dis. 2014;34(03):273–284.
   PubMedGoogle Scholar
• 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(1):S121–S130.
   PubMedGoogle Scholar
• Pinzani M. Pathophysiology of liver fibrosis. Dig Dis. 2015;33(4):492–497.
   PubMed Web of Science ®Google Scholar
• Berzigotti A, De Gottardi A, Vukotic R, et al. Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension. PLoS One. 2013;8(3):e58742.
   PubMed Web of Science ®Google Scholar
• Iwakiri Y. The molecules: mechanisms of arterial vasodilatation observed in the splanchnic and systemic circulation in portal hypertension. J Clin Gastroenterol. 2007;41(Supplement 3):S288–S294.
   PubMedGoogle Scholar
• Bolognesi M, Di Pascoli M, Verardo A, et al. Splanchnic vasodilation and hyperdynamic circulatory syndrome in cirrhosis. WJG. 2014;20(10):2555–2563.
   PubMed Web of Science ®Google Scholar
• Wiese S, Bendtsen F, Møller S. Cardiac biomarkers in cirrhotis and portal hypertension: relation to circulatory and cardiac dysfunction. In: Patel VB, Preedy VR, editors. Biomarkers in cardiovascular disease. 1st ed. Dordrecht: Springer; 2016. p. 573–599.
   Google Scholar
• Wiese S, Mortensen C, Gotze JP, et al. Cardiac and proinflammatory markers predict prognosis in cirrhosis. Liver Int. 2014;34(6):e19–e30.
   PubMed Web of Science ®Google Scholar
• Kimer N, Goetze JP, Bendtsen F, et al. New vasoactive peptides in cirrhosis: organ extraction and relation to the vasodilatory state. Eur J Clin Invest. 2014;44(5):441–452.
   PubMed Web of Science ®Google Scholar
• Di PM, Sacerdoti D, Pontisso P, et al. Molecular mechanisms leading to splanchnic vasodilation in liver cirrhosis. J Vasc Res. 2017;54(2):92–99.
   PubMed Web of Science ®Google Scholar
• Hobolth L, Bendtsen F, Møller S. Indications for portal pressure measurement in chronic liver disease. Scand J Gastroenterol. 2012;47(8-9):887–892.
   PubMed Web of Science ®Google Scholar
• de Franchis R. Expanding censensus in portal hypertension. Report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743–752.
   PubMed Web of Science ®Google Scholar
• Thabut D, Bureau C, Layese R, et al. Validation of Baveno VI criteria for screening and surveillance of esophageal varices in patients with compensated cirrhosis and a sustained response to antiviral therapy. Gastroenterology. 2019;156(4):997–1009.e5.
   PubMed Web of Science ®Google Scholar
• de Franchis R, Dell’era A. Invasive and noninvasive methods to diagnose portal hypertension and esophageal varices. Clin Liver Dis. 2014;18(2):293–302.
   PubMed Web of Science ®Google Scholar
• Bendtsen F, Krag A, Møller S. Treatment of acute variceal bleeding. Dig Liver Dis. 2008;40(5):328–336.
   PubMedGoogle Scholar
• D’amico G, Morabito A, D’Amico M, et al. Clinical states of cirrhosis and competing risks. J Hepatol. 2018;68(3):563–576.
   PubMed Web of Science ®Google Scholar
• Turco L, Villanueva C, La M,V, et al. Lowering portal pressure improves outcomes of patients with cirrhosis, with or without ascites: a meta-analysis. Clin Gastroenterol Hepatol. 2019;18(2):313–327.e6.
   PubMed Web of Science ®Google Scholar
• La MV, Abraldes JG, Raffa S, et al. Prognostic value of acute hemodynamic response to i.v. propranolol in patients with cirrhosis and portal hypertension. J Hepatol. 2009;51(2):274–287.
   Web of Science ®Google Scholar
• Villanueva C, Aracil C, Colomo A, et al. Acute hemodynamic response to beta-blockers and prediction of long-term outcome in primary prophylaxis of variceal bleeding. Gastroenterology. 2009;137(1):119–128.
   PubMed Web of Science ®Google Scholar
• D’amico G, Malizia G, Bosch J. Beta-blockers in 2016: still the safest and most useful drugs for portal hypertension? Hepatology. 2016;63(6):1771–1773.
   PubMed Web of Science ®Google Scholar
• Villanueva C, Albillos A, Genesca J, et al. Development of hyperdynamic circulation and response to beta-blockers in compensated cirrhosis with portal hypertension. Hepatology. 2016;63(1):197–206.
   PubMed Web of Science ®Google Scholar
• Oben JA, Roskams T, Yang S, et al. Hepatic fibrogenesis requires sympathetic neurotransmitters. Gut. 2004;53(3):438–445.
   PubMed Web of Science ®Google Scholar
• Trebicka J, Hennenberg M, Schulze PA, et al. Role of beta3-adrenoceptors for intrahepatic resistance and portal hypertension in liver cirrhosis. Hepatology. 2009;50(6):1924–1935.
   PubMed Web of Science ®Google Scholar
• Zacharias AP, Jeyaraj R, Hobolth L, et al. Carvedilol versus traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices. Cochrane Database Syst Rev. 2018;(10):CD011510.
   PubMedGoogle Scholar
• Malandris K, Paschos P, Katsoula A, et al. Carvedilol for prevention of variceal bleeding: a systematic review and meta-analysis. Ann Gastroenterol. 2019;32(3):287–297.
   PubMed Web of Science ®Google Scholar
• Hobolth L, Bendtsen F, Hansen EF, et al. Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis: a randomised study. Dig Liver Dis. 2014;46(3):251–256.
   PubMedGoogle Scholar
• Trebicka J, von HM, Lehmann J, et al. Assessment of beta-blocker response by expression of beta-Arrestin2 and RhoA/ROCK2 in antrum mucosa in cirrhotic patients. J Hepatol. 2016;64(6):1265–1273.
   PubMed Web of Science ®Google Scholar
• Augustin S, Gonzalez A, Badia L, et al. Long-term follow-up of hemodynamic responders to pharmacological therapy after variceal bleeding. Hepatology. 2012;56(2):706–714.
   PubMed Web of Science ®Google Scholar
• Tripathi D, Hayes P. Beta blockers in portal hypertension: new developments and controversies. Liver Int. 2014;34(5):655–667.
   PubMed Web of Science ®Google Scholar
• Bendtsen F, Møller S, Krag A. Variceal rebleeding: drugs, endoscopy or both? In: de Franchis R, Dell’era A, editors. Variceal hemorrhage. 1st ed. London: Springer; 2014. p. 213–228.
   Google Scholar
• Nevens F. Novel approaches to reducing the risk of variceal hemorrhage. Dig Dis. 2017;35(4):397–401.
   PubMed Web of Science ®Google Scholar
• Ioannou G, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev. 2003;(1):CD002147.
   PubMedGoogle Scholar
• Zhou X, Tripathi D, Song T, et al. Terlipressin for the treatment of acute variceal bleeding: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018;97(48):e13437.
   PubMed Web of Science ®Google Scholar
• Pose E, Trebicka J, Mookerjee RP, et al. Statins: old drugs as new therapy for liver diseases? J Hepatol. 2019;70(1):194–202.
   PubMed Web of Science ®Google Scholar
• Abraldes JG, Villanueva C, Aracil C, 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):1160–1170.
   PubMed Web of Science ®Google Scholar
• Tripathi DM, Vilaseca M, Lafoz E, et al. Simvastatin prevents progression of acute on chronic liver failure in rats with cirrhosis and portal hypertension. Gastroenterology. 2018;155(5):1564–1577.
   PubMed Web of Science ®Google Scholar
• Schwabl P, Hambruch E, Seeland BA, et al. The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction. J Hepatol. 2017;66(4):724–733.
   PubMed Web of Science ®Google Scholar
• Tandon P, Inayat I, Tal M, et al. Sildenafil has no effect on portal pressure but lowers arterial pressure in patients with compensated cirrhosis. Clin Gastroenterol Hepatol. 2010;8(6):546–549.
   PubMed Web of Science ®Google Scholar
• Tandon P, Abraldes JG, Berzigotti A, et al. Renin-angiotensin-aldosterone inhibitors in the reduction of portal pressure: a systematic review and meta-analysis. J Hepatol. 2010;52(2):273–282.
   Google Scholar
• Shim KY, Eom YW, Kim MY, et al. Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension. Korean J Intern Med. 2018;33(3):453–461.
   PubMed Web of Science ®Google Scholar
• Bernardi M, Moreau R, Angeli P, et al. Mechanisms of decompensation and organ failure in cirrhosis: from peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol. 2015;63(1272):1284.
   Google Scholar
• Hernaez R, Sola E, Moreau R, et al. Acute-on-chronic liver failure: an update. Gut. 2017;66(3):541–553.
   PubMed Web of Science ®Google Scholar
• Møller S, Iversen JS, Henriksen JH, et al. Reduced baroreflex sensitivity in alcoholic cirrhosis:relations to hemodynamics and humoral systems. Am J Physiol Heart Circ Physiol. 2007;292(6):H2966–H2972.
   PubMed Web of Science ®Google Scholar
• Møller S, Mortensen C, Bendtsen F, et al. Cardiac sympathetic imaging with mIBG in cirrhosis and portal hypertension: relation to autonomic and cardiac function. Am J Physiol Gastrointest Liver Physiol. 2012;303(11):G1228–G1235.
   PubMed Web of Science ®Google Scholar
• Di SC, Milazzo V, Milan A, et al. The role of autonomic dysfunction in cirrhotic patients before and after liver transplantation. Review of the literature. Liver Int. 2016;36(8):1081–1089.
   PubMed Web of Science ®Google Scholar
• Tazi KA, Moreau R, Heller J, et al. Changes in protein kinase C isoforms in association with vascular hyporeactivity in cirrhotic rat aortas. Gastroenterology. 2000;119(1):201–210.
   PubMed Web of Science ®Google Scholar
• Ferlitsch A, Pleiner J, Mittermayer F, et al. Vasoconstrictor hyporeactivity can be reversed by antioxidants in patients with advanced alcoholic cirrhosis of the liver and ascites. Crit Care Med. 2005;33(9):2028–2033.
   PubMed Web of Science ®Google Scholar
• Wiest R, Groszmann RJ. Nitric oxide and portal hypertension: its role in the regulation of intrahepatic and splanchnic vascular resistance. Semin Liver Dis. 1999;19(04):411–426.
   PubMedGoogle Scholar
• Tazi KA, Barriere E, Moreau R, et al. Role of shear stress in aortic eNOS up-regulation in rats with biliary cirrhosis. Gastroenterology. 2002;122(7):1869–1877.
   PubMed Web of Science ®Google Scholar
• Lopez-Talavera JC, Merrill WW, Groszmann RJ. Tumor necrosis factor alpha: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats. Gastroenterology. 1995;108(3):761–767.
   PubMed Web of Science ®Google Scholar
• Munoz J, Albillos A, Perezparamo M, et al. Factors mediating the hemodynamic effects of tumor necrosis factor-alpha in portal hypertensive rats. Amer J Physiol Gastrointest L. 1999;39(3):G687–G693.
   Google Scholar
• Reiberger T, Ferlitsch A, Payer BA, et al. Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis. J Hepatol. 2013;58(5):911–921.
   PubMed Web of Science ®Google Scholar
• Wiest R, Lawson M, Geuking M. Pathological bacterial translocation in liver cirrhosis. J Hepatol. 2014;60(1):197–209.
   PubMed Web of Science ®Google Scholar
• Bajaj JS, O’Leary JG, Wong F, et al. Bacterial infections in end-stage liver disease: current challenges and future directions. Gut. 2012;61(8):1219–1225.
   PubMed Web of Science ®Google Scholar
• Leithead JA, Ferguson JW, Bates CM, et al. The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure. Gut. 2009;58(3):443–449.
   PubMed Web of Science ®Google Scholar
• Møller S, Henriksen JH, Bendtsen F. Ascites: pathogenesis and therapeutic principles. Scand J Gastroenterol. 2009;44(8):902–911.
   PubMed Web of Science ®Google Scholar
• Gines P, Angeli P, Lenz K, et al. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53(3):397–417.
   PubMed Web of Science ®Google Scholar
• Angeli P, Sanyal A, Møller S, et al. Current limits and future challenges in the management of renal dysfunction in patients with cirrhosis: report from the International Club of Ascites. Liver Int. 2013;33(1):16–23.
   PubMed Web of Science ®Google Scholar
• Schrier RW. Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. Am J Med. 2006;119(7):S47–S53.
   PubMedGoogle Scholar
• Henriksen JH, Kiszka-Kanowitz M, Bendtsen F, et al. Review article: volume expansion in patients with cirrhosis. Aliment Pharmacol Ther. 2002;16(s5):12–23.
   PubMedGoogle Scholar
• Bernardi M, Santi L. Renal sodium retention in pre-ascitic cirrhosis: the more we know about the puzzle, the more it becomes intricate. J Hepatol. 2010;53(5):790–792.
   PubMed Web of Science ®Google Scholar
• Bosch J, Iwakiri Y. The portal hypertension syndrome: etiology, classification, relevance, and animal models. Hepatol Int. 2018;12(S1):1–10.
   PubMedGoogle Scholar
• Claria J, Stauber RE, Coenraad MJ, et al. Systemic inflammation in decompensated cirrhosis: characterization and role in acute-on-chronic liver failure. Hepatology. 2016;64(4):1249–1264.
   PubMed Web of Science ®Google Scholar
• Liu H, Schuelert N, McDougall JJ, et al. Central neural activation of hyperdynamic circulation in portal hypertensive rats depends on vagal afferent nerves. Gut. 2008;57(7):966–973.
   PubMed Web of Science ®Google Scholar
• EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406–460.
   PubMed Web of Science ®Google Scholar
• Bureau C, Thabut D, Oberti F, et al. Transjugular Intrahepatic portosystemic shunts with covered stents increase transplant-free survival of patients with cirrhosis and recurrent ascites. Gastroenterology. 2017;152(1):157–163.
   PubMed Web of Science ®Google Scholar
• Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48(6):2064–2077.
   PubMed Web of Science ®Google Scholar
• Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.
   PubMed Web of Science ®Google Scholar
• Møller S, Krag A, Bendtsen F. Kidney injury in cirrhosis: pathophysiological and therapeutic aspects of hepatorenal syndromes. Liver Int. 2014;34(8):1153–1163.
   PubMed Web of Science ®Google Scholar
• Angeli P, Garcia-Tsao G, Nadim MK, et al. News in pathophysiology, definition and classification of hepatorenal syndrome: a step beyond the International Club of Ascites (ICA) consensus document. J Hepatol. 2019;71(811):822.
   Google Scholar
• Schrier RW, Shchekochikhin D, Gines P. Renal failure in cirrhosis: prerenal azotemia, hepatorenal syndrome and acute tubular necrosis. Nephrol Dial Transplant. 2012;27(7):2625–2628.
   PubMed Web of Science ®Google Scholar
• Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009;361(13):1279–1290.
   PubMed Web of Science ®Google Scholar
• Serste T, Gustot T, Rautou PE, et al. Severe hyponatremia is a better predictor of mortality than MELDNa in patients with cirrhosis and refractory ascites. J Hepatol. 2012;57(2):274–280.
   PubMed Web of Science ®Google Scholar
• Piano S, Tonon M, Angeli P. Management of ascites and hepatorenal syndrome. Hepatol Int. 2018;12(S1):122–134.
   PubMed Web of Science ®Google Scholar
• Bernardi M, Caraceni P. Novel perspectives in the management of decompensated cirrhosis. Nat Rev Gastroenterol Hepatol. 2018;15(12):753–764.
   PubMed Web of Science ®Google Scholar
• Stadlbauer VP, Wright GA, Banaji M, et al. Relationship between activation of the sympathetic nervous system and renal blood flow autoregulation in cirrhosis. Gastroenterology. 2008;134(1):111–119.
   PubMed Web of Science ®Google Scholar
• Schmidt LE, Ring-Larsen H. Vasoconstrictor therapy for hepatorenal syndrome in liver cirrhosis. CPD. 2006;12(35):4637–4647.
   Google Scholar
• Mattos AZ, Schacher FC, Mattos AA. Vasoconstrictors in hepatorenal syndrome – a critical review. Ann Hepatol. 2019;18(2):287–290.
   PubMed Web of Science ®Google Scholar
• Israelsen M, Krag A, Allegretti AS, et al. Terlipressin versus other vasoactive drugs for hepatorenal syndrome. Cochrane Database Syst Rev. 2017;(9):CD011532.
   PubMed Web of Science ®Google Scholar
• Krag A, Møller S. Safety of terlipressin for hepatorenal syndrome. In: Gerbes A, editor. Ascites, hyponatremia and hepatrenal syndrome: progress in treatment. 1st ed. Basel: Karger; 2011. p. 178–188.
   Google Scholar
• Francoz C, Durand F, Kahn JA, et al. Hepatorenal syndrome. CJASN. 2019;14(5):774–781.
   PubMed Web of Science ®Google Scholar
• Krag A, Bendtsen F, Pedersen EB, et al. Effects of terlipressin on the aquaretic system – evidence of antidiuretic effects. Am J Physiol Renal Physiol. 2008;295(5):F1295–F1300.
   PubMed Web of Science ®Google Scholar
• Paine CH, Biggins SW, Pichler RH. Albumin in cirrhosis: more than a colloid. Curr Treat Options Gastro. 2019;17(2):231–243.
   PubMedGoogle Scholar
• Wong F, Watson H, Gerbes A, et al. Satavaptan for the management of ascites in cirrhosis: efficacy and safety across the spectrum of ascites severity. Gut. 2012;61(1):108–116.
   PubMed Web of Science ®Google Scholar
• Lehrich RW, Ortiz-Melo DI, Patel MB, et al. Role of vaptans in the management of hyponatremia. Am J Kidney Dis. 2013;62(2):364–376.
   PubMed Web of Science ®Google Scholar
• Cartin-Ceba R, Krowka MJ. Pulmonary complications of portal hypertension. Clin Liver Dis. 2019;23(4):683–711.
   PubMed Web of Science ®Google Scholar
• Raevens S, Geerts A, Van Steenkiste C, et al. Hepatopulmonary syndrome and portopulmonary hypertension: recent knowledge in pathogenesis and overview of clinical assessment. Liver Int. 2015;35(6):1646–1660.
   PubMed Web of Science ®Google Scholar
• Zhang M, Luo B, Chen SJ, et al. Endothelin-1 stimulation of endothelial nitric oxide synthase in the pathogenesis of hepatopulmonary syndrome. Am J Physiol. 1999;277(5):G944–G952.
   PubMedGoogle Scholar
• Luo B, Liu L, Tang L, et al. Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: a potential mechanism in experimental hepatopulmonary syndrome. J Hepatol. 2003;38(5):556–563.
   PubMed Web of Science ®Google Scholar
• Zhang J, Ling Y, Luo B, et al. Analysis of pulmonary heme oxygenase-1 and nitric oxide synthase alterations in experimental hepatopulmonary syndrome. Gastroenterology. 2003;125(5):1441–1451.
   PubMed Web of Science ®Google Scholar
• Söderman C, Leone A, Furst V, et al. Endogenous nitric oxide in exhaled air from patients with liver cirrhosis. Scand J Gastroenterol. 1997;32(6):591–597.
   PubMed Web of Science ®Google Scholar
• Afzelius P, Bazeghi N, Bie P, et al. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension. Liver Int. 2011;31(9):1381–1387.
   PubMed Web of Science ®Google Scholar
• Arguedas MR, Drake BB, Kapoor A, et al. Carboxyhemoglobin levels in cirrhotic patients with and without hepatopulmonary syndrome. Gastroenterology. 2005;128(2):328–333.
   PubMed Web of Science ®Google Scholar
• Raevens S, Geerts A, Paridaens A, et al. Placental growth factor inhibition targets pulmonary angiogenesis and represents a therapy for hepatopulmonary syndrome in mice. Hepatology. 2018;68(2):634–651.
   PubMed Web of Science ®Google Scholar
• Horvatits T, Drolz A, Roedl K, et al. vWF, a screening tool for detection of hepatopulmonary syndrome in patients with liver cirrhosis. J Hepatol. 2014;61(3):544–549.
   PubMed Web of Science ®Google Scholar
• Raevens S, Fallon MB. Potential clinical targets in hepatopulmonary syndrome: lessons from experimental models. Hepatology. 2018;68(5):2016–2028.
   PubMed Web of Science ®Google Scholar
• Brussino L, Bucca C, Morello M, et al. Effect on dyspnoea and hypoxaemia of inhaled N(G)-nitro-L-arginine methyl ester in hepatopulmonary syndrome. Lancet. 2003;362(9377):43–44.
   PubMed Web of Science ®Google Scholar
• Gomez FP, Barbera JA, Roca J, et al. Effects of nebulized N(G)-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome. Hepatology. 2006;43(5):1084–1091.
   PubMed Web of Science ®Google Scholar
• Gupta S, Faughnan ME, Lilly L, et al. Norfloxacin therapy for hepatopulmonary syndrome: a pilot randomized controlled trial. Clin Gastroenterol Hepatol. 2010;8(12):1095–1098.
   PubMed Web of Science ®Google Scholar
• Liu L, Liu N, Zhao Z, et al. TNF-alpha neutralization improves experimental hepatopulmonary syndrome in rats. Liver Int. 2012;32(6):1018–1026.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Roisin R, Krowka MJ, Herve P, et al. Pulmonary-hepatic vascular disorders (PHD). Eur Respir J. 2004;24(5):861–880.
   PubMed Web of Science ®Google Scholar
• Roberts KE, Fallon MB, Krowka MJ, et al. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. Am J Respir Crit Care Med. 2009;179(9):835–842.
   PubMed Web of Science ®Google Scholar
• Cody RJ, Haas GJ, Binkley PF, et al. Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure. Circulation. 1992;85(2):504–509.
   PubMed Web of Science ®Google Scholar
• Barnes PJ. Endothelins and pulmonary diseases. J Appl Physiol. 1994;77(3):1051–1059.
   PubMed Web of Science ®Google Scholar
• Talwalkar JA, Swanson KL, Krowka MJ, et al. Prevalence of spontaneous portosystemic shunts in patients with portopulmonary hypertension and effect on treatment. Gastroenterology. 2011;141(5):1673–1679.
   PubMed Web of Science ®Google Scholar
• Machicao VI, Balakrishnan M, Fallon MB. Pulmonary complications in chronic liver disease. Hepatology. 2014;59(4):1627–1637.
   PubMed Web of Science ®Google Scholar
• AbuHalimeh B, Krowka MJ, Tonelli AR. Treatment barriers in portopulmonary hypertension. Hepatology. 2019;69(1):431–443.
   PubMed Web of Science ®Google Scholar
• Kuntzen C, Gulberg V, Gerbes AL. Use of a mixed endothelin receptor antagonist in portopulmonary hypertension: a safe and effective therapy? Gastroenterology. 2005;128(1):164–168.
   PubMed Web of Science ®Google Scholar
• Hoeper MM, Halank M, Marx C, et al. Bosentan therapy for portopulmonary hypertension. Eur Respir J. 2005;25(3):502–508.
   PubMed Web of Science ®Google Scholar
• Reichenberger F, Voswinckel R, Steveling E, et al. Sildenafil treatment for portopulmonary hypertension. Eur Respir J. 2006;28(3):563–567.
   PubMed Web of Science ®Google Scholar
• Simbrunner B, Mandorfer M, Trauner M, et al. Gut-liver axis signaling in portal hypertension. Wjg. 2019;25(39):5897–5917.
   PubMed Web of Science ®Google Scholar