Hepatorenal Syndrome
By:
Andrew DavenportUCL Department of Renal Medicine, Royal Free Hospital, University College London, London, United Kingdom

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  • 1

    Earley LE: Presentation of diagnostic criteria of the hepatorenal syndrome. In: Hepatorenal ascites formation in cirrhosis: role of atrial natriuretic factor. Syndrome, edited by Bartoli E, Chiandussi L, Padova, Piccin Medical Books, 1979, pp 495504

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  • 2

    Arroyo V, Ginès P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al..: Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology 23: 164176, 1996 PubMed

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  • 3

    Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V: Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut 56: 13101318, 2007 PubMed

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  • 4

    Angeli P, Ginès P, Wong F, Bernardi M, Boyer TD, Gerbes A, et al..: Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol 62: 968974, 2015 PubMed

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  • 5

    Trawalé JM, Paradis V, Rautou PE, Francoz C, Escolano S, Sallée M, et al..: The spectrum of renal lesions in patients with cirrhosis: a clinicopathological study. Liver Int 30: 725732, 2010 PubMed

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  • 6

    Davenport A, Sheikh MF, Lamb E, Agarwal B, Jalan R: Acute kidney injury in acute-on-chronic liver failure: where does hepatorenal syndrome fit? Kidney Int 92: 10581070, 2017 PubMed

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  • 7

    Martin P-Y, Ginès P, Schrier RW: Nitric oxide as a mediator of hemodynamic abnormalities and sodium and water retention in cirrhosis. N Engl J Med 339: 533541, 1998 PubMed

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  • 8

    Ginès P, Schrier RW: Renal failure in cirrhosis. N Engl J Med 361: 12791290, 2009 PubMed

  • 9

    Solà E, Ginès P: Renal and circulatory dysfunction in cirrhosis: current management and future perspectives. J Hepatol 53: 11351145, 2010 PubMed

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  • 10

    Kapoor D, Redhead DN, Hayes PC, Webb DJ, Jalan R: Systemic and regional changes in plasma endothelin following transient increase in portal pressure. Liver Transpl 9: 3239, 2003 PubMed

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  • 11

    Kastelan S, Ljubicic N, Kastelan Z, Ostojic R, Uravic M: The role of duplex-doppler ultrasonography in the diagnosis of renal dysfunction and hepatorenal syndrome in patients with liver cirrhosis. Hepatogastroenterology 51: 14081412, 2004 PubMed

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  • 12

    Koppel MH, Coburn JW, Mims MM, Goldstein H, Boyle JD, Rubini ME: Transplantation of cadaveric kidneys from patients with hepatorenal syndrome. Evidence for the functionalnature of renal failure in advanced liver disease. N Engl J Med 280: 13671371, 1969 PubMed

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  • 13

    Iwatsuki S, Popovtzer MM, Corman JL, Ishikawa M, Putnam CW, Katz FH, et al..: Recovery from “hepatorenal syndrome” after orthotopic liver transplantation. N Engl J Med 289: 11551159, 1973 PubMed

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  • 14

    Kalambokis GN, Tsiakas I, Christaki M, et al..: Systemic hemodynamic response to terlipressin predicts development of hepatorenal syndrome and survival in advanced cirrhosis. Eur J Gastroenterol Hepatol 30: 659667, 2018.

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  • 15

    Salerno F, Navickis RJ, Wilkes MM: Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis. BMC Gastroenterol 15: 167, 2015 PubMed

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  • 16

    Fabrizi F, Dixit V, Martin P: Meta-analysis: terlipressin therapy for the hepatorenal syndrome. Aliment Pharmacol Ther 24: 935944, 2006 PubMed

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  • 17

    Krag A, Bendtsen F, Henriksen JH, Møller S: Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites. Gut 59: 105110, 2010 PubMed

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  • 18

    Sersté T, Melot C, Francoz C, Durand F, Rautou PE, Valla D, et al..: Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology 52: 10171022, 2010 PubMed

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  • 19

    Mandorfer M, Bota S, Schwabl P, Bucsics T, Pfisterer N, Kruzik M, et al..: Nonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology 146: 168090.e1, 2014 PubMed

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  • 20

    Acevedo J, Fernández J, Prado V, Silva A, Castro M, Pavesi M, et al..: Relative adrenal insufficiency in decompensated cirrhosis: Relationship to short-term risk of severe sepsis, hepatorenal syndrome, and death. Hepatology 58: 17571765, 2013 PubMed

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  • 21

    Theocharidou E, Krag A, Bendtsen F, Møller S, Burroughs AK: Cardiac dysfunction in cirrhosis: does adrenal function play a role? A hypothesis. Liver Int 32: 13271332, 2012 PubMed

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  • 22

    Navasa M, Follo A, Filella X, Jiménez W, Francitorra A, Planas R, et al..: Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in cirrhosis: relationship with the development of renal impairment and mortality. Hepatology 27: 12271232, 1998 PubMed

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  • 23

    Weichselbaum L, Gustot T: The organs in acute-on-chronic liver failure. Semin Liver Dis 36: 174180, 2016 PubMed

  • 24

    Davenport A, Argawal B, Wright G, Mantzoukis K, Dimitrova R, Davar J, et al.: Can non-invasive measurements aid clinical assessment of volume in patients with cirrhosis? World J Hepatol 5: 433438, 2013 PubMed

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  • 25

    Umgelter A, Reindl W, Franzen M, Lenhardt C, Huber W, Schmid RM: Renal resistive index and renal function before and after paracentesis in patients with hepatorenal syndrome and tense ascites. Intensive Care Med 35: 152156, 2009 PubMed

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  • 26

    Shah N, Mohamed FE, Jover-Cobos M, Macnaughtan J, Davies N, Moreau R, et al..: Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis. Liver Int 33: 398409, 2013 PubMed

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  • 27

    Barreto R, Fagundes C, Guevara M, Solà E, Pereira G, Rodríguez E, et al..: Type-1 hepatorenal syndrome associated with infections in cirrhosis: natural history, outcome of kidney function, and survival. Hepatology 59: 15051513, 2014 PubMed

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  • 28

    Klein CL, Hoke TS, Fang WF, Altmann CJ, Douglas IS, Faubel S: Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy. Kidney Int 74: 901909, 2008 PubMed

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  • 29

    Skrypnyk NI, Gist KM, Okamura K, Montford JR, You Z, Yang H, et al..: IL-6-mediated hepatocyte production is the primary source of plasma and urine neutrophil gelatinase-associated lipocalin during acute kidney injury. Kidney Int 97: 966979, 2020 PubMed

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  • 30

    Savino JA, Cerabona T, Agarwal N, Byrne D: Manipulation of ascitic fluid pressure in cirrhotics to optimize hemodynamic and renal function. Ann Surg 208: 504511, 1988 PubMed

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  • 31

    Davenport A, Ahmad J, Al-Khafaji A, Kellum JA, Genyk YS, Nadim MK: Medical management of hepatorenal syndrome. Nephrol Dial Transplant 27: 3441, 2012 PubMed

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  • 32

    Wong F, Nadim MK, Kellum JA, Salerno F, Bellomo R, Gerbes A, et al..: Working party proposal for a revised classification system of renal dysfunction in patients with cirrhosis. Gut 60: 702709, 2011 PubMed

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  • 33

    Piano S, Rosi S, Maresio G, Fasolato S, Cavallin M, Romano A, et al..: Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites. J Hepatol 59: 482489, 2013 PubMed

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  • 34

    Garcia-Tsao G, Parikh CR, Viola A: Acute kidney injury in cirrhosis. Hepatology 48: 20642077, 2008 PubMed

  • 35

    Fang J-T, Tsai M-H, Tian Y-C, Jenq CC, Lin CY, Chen YC, et al..: Outcome predictors and new score of critically ill cirrhotic patients with acute renal failure. Nephrol Dial Transplant 23: 19611969, 2008 PubMed

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  • 36

    Tsien CD, Rabie R, Wong F: Acute kidney injury in decompensated cirrhosis. Gut 62: 131137, 2013 PubMed

  • 37

    Amin AA, Alabsawy EI, Jalan R, Davenport A: Epidemiology, pathophysiology, and management of hepatorenal syndrome. Semin Nephrol 39: 1730, 2019 PubMed

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  • 38

    Wong F, Pappas SC, Curry MP, Reddy KR, Rubin RA, Porayko MK, et al.; CONFIRM Study Investigators: Terlipressin plus albumin. N Engl J Med 384: 818828, 2021 PubMed

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  • 39

    Wong F, Boyer TD, Sanyal AJ, Pappas SC, Escalante S, Jamil K: Reduction in acute kidney injury stage predicts survival in patients with type-1 hepatorenal syndrome. Nephrol Dial Transplant 35: 15541561, 2020 PubMed

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  • 40

    Davenport A, Cholongitas E, Xirouchakis E, Burroughs AK: Pitfalls in assessing renal function in patients with cirrhosis: potential inequity for access to treatment of hepatorenal failure and liver transplantation. Nephrol Dial Transplant 26: 27352742, 2011 PubMed

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  • 41

    Davenport A: AKI in a patient with cirrhosis and ascites. Clin J Am Soc Nephrol 7: 20412048, 2012 PubMed

  • 42

    Stevens LA, Coresh J, Greene T, Levey AS: Assessing kidney function: measured and estimated glomerular filtration rate. N Engl J Med 354: 24732483, 2006 PubMed

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  • 43

    Nadim MK, Kellum JA, Davenport A, Wong F, Davis C, Pannu N, et al.; ADQI Workgroup: Hepatorenal syndrome: the 8th International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 16: R23, 2012 PubMed

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  • 44

    Seo YS, Park SY, Kim MY, Kim SG, Park JY, Yim HJ, et al..: Serum cystatin C level: an excellent predictor of mortality in patients with cirrhotic ascites. J Gastroenterol Hepatol 33: 910917, 2018 PubMed

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  • 45

    Krones E, Fickert P, Zitta S, Neunherz S, Artinger K, Reibnegger G, et al..: The chronic kidney disease epidemiology collaboration equation combining creatinine and cystatin C accurately assesses renal function in patients with cirrhosis. BMC Nephrol 16: 196, 2015 PubMed

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  • 46

    Belcher JM, Sanyal AJ, Peixoto AJ, Perazella MA, Lim J, Thiessen-Philbrook H, et al.; TRIBE-AKI Consortium: Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology 60: 622632, 2014 PubMed

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  • 47

    Alsaad AA, Wadei HM: Fractional excretion of sodium in hepatorenal syndrome: clinical and pathological correlation. World J Hepatol 8: 14971501, 2016 PubMed

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  • 48

    Carvounis CP, Nisar S, Guro-Razuman S: Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure. Kidney Int 62: 22232229, 2002 PubMed

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  • 49

    Patidar KR, Kang L, Bajaj JS, Carl D, Sanyal AJ: Fractional excretion of urea: a simple tool for the differential diagnosis of acute kidney injury in cirrhosis. Hepatology 68: 224233, 2018 PubMed

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  • 50

    Sanguankeo A, Upala S: Limitations of fractional excretion of urea in clinical practice. Hepatology 69: 1357, 2019 PubMed

  • 51

    Belcher JM, Sanyal AJ, Garcia-Tsao G, Ansari N, Coca SG, Shlipak MG, et al..: Early trends in cystatin C and outcomes in patients with cirrhosis and acute kidney injury. Int J Nephrol 2014: 708585, 2014 PubMed

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  • 52

    Ariza X, Solà E, Elia C, Barreto R, Moreira R, Morales-Ruiz M, et al..: Analysis of a urinary biomarker panel for clinical outcomes assessment in cirrhosis. PLoS One 10: e0128145, 2015 PubMed

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  • 53

    Watany MM, Hagag RY, Okda HI: Circulating miR-21, miR-210 and miR-146a as potential biomarkers to differentiate acute tubular necrosis from hepatorenal syndrome in patients with liver cirrhosis: a pilot study. Clin Chem Lab Med 56: 739747, 2018 PubMed

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  • 54

    Ariza X, Graupera I, Coll M, Solà E, Barreto R, García E, et al.; CANONIC Investigators, EASL CLIF Consortium: Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis. J Hepatol 65: 5765, 2016 PubMed

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  • 55

    Huelin P, Solà E, Elia C, Solé C, Risso A, Moreira R, et al..: Neutrophil gelatinase-associated lipocalin for assessment of acute kidney injury in cirrhosis: a prospective study. Hepatology 70: 319333, 2019 PubMed

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  • 56

    Arroyo V, Jiménez W: Complications of cirrhosis. II. Renal and circulatory dysfunction. Lights and shadows in an important clinical problem. J Hepatol 32[Suppl]: 157170, 2000 PubMed

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  • 57

    Ginès P, Arroyo V: Paracentesis in the management of cirrhotic ascites. J Hepatol 17[Suppl 2]: S14S18, 1993 PubMed

  • 58

    Sort P, Navasa M, Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, et al..: Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 341: 403409, 1999 PubMed

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  • 59

    China L, Freemantle N, Forrest E, Kallis Y, Ryder SD, Wright G, et al.; ATTIRE Trial Investigators: A randomized trial of albumin infusions in hospitalized patients with cirrhosis. N Engl J Med 384: 808817, 2021 PubMed

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  • 60

    Cade R, Wagemaker H, Vogel S, Mars D, Hood-Lewis D, Privette M, et al..: Hepatorenal syndrome: studies of the effect of vascular volume and intraperitoneal pressure on renal and hepatic function. Am J Med 82: 427438, 1987 PubMed

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  • 61

    Jalan R, Redhead DN, Thomas HW, Henderson N, O’Rourke K, Dillon JF, et al..: Mechanisms of changes in renal handling of sodium following transjugular intrahepatic portal systemic stent-shunt (TIPSS). Eur J Gastroenterol Hepatol 8: 11111116, 1996 PubMed

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  • 62

    Jalan R, Lui HF, Redhead DN, Hayes PC: TIPSS 10 years on. Gut 46: 578581, 2000 PubMed

  • 63

    Kang DJ, Kakiyama G, Betrapally NS, Herzog J, Nittono H, Hylemon PB, et al..: Rifaximin exerts beneficial effects independent of its ability to alter microbiota composition. Clin Transl Gastroenterol 7: e187, 2016 PubMed

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  • 64

    Caraceni P, Vargas V, Solà E, Alessandria C, de Wit K, Trebicka J, et al.; Liverhope Consortium: The use of rifaximin in patients with cirrhosis. Hepatology 74: 16601673, 2021 10.1002/hep.31708PubMed

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  • 65

    Sanyal AJ, Boyer TD, Frederick RT, Wong F, Rossaro L, Araya V, et al..: Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies. Aliment Pharmacol Ther 45: 13901402, 2017 PubMed

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  • 66

    Adebayo D, Morabito V, Davenport A, Jalan R: Renal dysfunction in cirrhosis is not just a vasomotor nephropathy. Kidney Int 87: 509515, 2015 PubMed

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  • 67

    Nadim MK, Durand F, Kellum JA, Levitsky J, O’Leary JG, Karvellas CJ, et al..: Management of the critically ill patient with cirrhosis: a multidisciplinary perspective. J Hepatol 64: 717735, 2016 PubMed

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  • 68

    Zheng J-N, Han Y-J, Zou T-T, Zhou YJ, Sun DQ, Zhong JH, et al..: Comparative efficacy of vasoconstrictor therapies for type 1 hepatorenal syndrome: a network meta-analysis. Expert Rev Gastroenterol Hepatol 11: 10091018, 2017 PubMed

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  • 69

    European Association for the Study of Liver Diseases: EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol 33: 591598, 2018

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  • 70

    Jamil K, Pappas SC, Devarakonda KR: In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V1 and V2. J Exp Pharmacol 10: 17, 2017 PubMed

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  • 71

    Fabrizi F, Aghemo A, Messa P: Hepatorenal syndrome and novel advances in its management. Kidney Blood Press Res 37: 588601, 2013 PubMed

  • 72

    Nassar Junior AP, Farias AQ, D’ Albuquerque LA, Carrilho FJ, Malbouisson LM: Terlipressin versus norepinephrine in the treatment of hepatorenal syndrome: a systematic review and meta-analysis. PLoS One 9: e107466, 2014 PubMed

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  • 73

    Mattos AZ, Mattos AA, Ribeiro RA: Terlipressin versus noradrenaline in the treatment of hepatorenal syndrome: systematic review with meta-analysis and full economic evaluation. Eur J Gastroenterol Hepatol 28: 345351, 2016 PubMed

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  • 74

    Wong F, Pantea L, Sniderman K: Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology 40: 5564, 2004 PubMed

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  • 75

    Cavallin M, Kamath PS, Merli M, Fasolato S, Toniutto P, Salerno F, et al.; Italian Association for the Study of the Liver Study Group on Hepatorenal Syndrome: Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: a randomized trial. Hepatology 62: 567574, 2015 PubMed

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  • 76

    Best LM, Freeman SC, Sutton AJ, Cooper NJ, Tng EL, Csenar M, et al..: Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev 9: CD013103, 2019 PubMed

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  • 77

    Reiberger T: When should we stop treatment with terlipressin and albumin for patients with hepatorenal syndrome? Clin Gastroenterol Hepatol 16: 17101711, 2018 PubMed

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  • 78

    Facciorusso A, Chandar AK, Murad MH, Prokop LJ, Muscatiello N, Kamath PS, et al..: Comparative efficacy of pharmacological strategies for management of type 1 hepatorenal syndrome: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol 2: 94102, 2017 PubMed

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  • 79

    Arora V, Maiwall R, Rajan V, Jindal A, Muralikrishna Shasthry S, Kumar G, et al..: Terlipressin is superior to noradrenaline in the management of acute kidney injury in acute on chronic liver failure. Hepatology 71: 600610, 2020 PubMed

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  • 80

    Thomson MJ, Taylor A, Sharma P, Lok AS, Tapper EB: Limited progress in hepatorenal syndrome (HRS) reversal and survival 2002-2018: a systematic review and meta-analysis. Dig Dis Sci 65: 15391548, 2020 PubMed

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  • 81

    Boyer TD, Sanyal AJ, Garcia-Tsao G, Blei A, Carl D, Bexon AS, et al.; Terlipressin Study Group: Predictors of response to terlipressin plus albumin in hepatorenal syndrome (HRS) type 1: relationship of serum creatinine to hemodynamics. J Hepatol 55: 315321, 2011 PubMed

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  • 82

    Snowdon VK, Lachlan NJ, Hoy AM, Hadoke PW, Semple SI, Patel D, et al..: Serelaxin as a potential treatment for renal dysfunction in cirrhosis: preclinical evaluation and results of a randomized phase 2 trial. PLoS Med 14: e1002248, 2017 PubMed

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  • 83

    Zhang Z, Maddukuri G, Jaipaul N, Cai CX: Role of renal replacement therapy in patients with type 1 hepatorenal syndrome receiving combination treatment of vasoconstrictor plus albumin. J Crit Care 30: 969974, 2015 PubMed

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  • 84

    Wong F, Raina N, Richardson R: Molecular adsorbent recirculating system is ineffective in the management of type 1 hepatorenal syndrome in patients with cirrhosis with ascites who have failed vasoconstrictor treatment. Gut 59: 381386, 2010 PubMed

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  • 85

    Valerio C, Theocharidou E, Davenport A, Agarwal B: Human albumin solution for patients with cirrhosis and acute on chronic liver failure: beyond simple volume expansion. World J Hepatol 8: 345354, 2016 PubMed

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