Current and future pharmacological therapies for managing cirrhosis and its complications
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摘要
Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. Pub Med/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.
Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. Pub Med/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.
Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. Pub Med/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.
引文
1 Tsochatzis EA,Bosch J,Burroughs AK.Liver cirrhosis.Lancet 2014;383:1749-1761[PMID:24480518DOI:10.1016/S0140-6736(14)60121-5]
2 Blachier M,Leleu H,Peck-Radosavljevic M,Valla DC,Roudot-Thoraval F.The burden of liver disease in Europe:A review of available epidemiological data.J Hepatol 2013;58:593-608[PMID:23419824DOI:10.1016/j.jhep.2012.12.005]
3 Williams R,Aspinall R,Bellis M,Camps-Walsh G,Cramp M,Dhawan A,Ferguson J,Forton D,Foster G,Gilmore I,Hickman M,Hudson M,Kelly D,Langford A,Lombard M,Longworth L,Martin N,Moriarty K,Newsome P,O'Grady J,Pryke R,Rutter H,Ryder S,Sheron N,Smith T.Addressing liver disease in the UK:A blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol,obesity,and viral hepatitis.Lancet 2014;384:1953-1997[PMID:25433429 DOI:10.1016/S0140-6736(14)61838-9]
4 Moctezuma-Velazquez C,Kalainy S,Abraldes JG.Beta-blockers in patients with advanced liver disease:Has the dust settled?Liver Transpl 2017;23:1058-1069[PMID:28590564 DOI:10.1002/lt.24794]
5 de Franchis R;Baveno VI Faculty.Expanding consensus in portal hypertension:Report of the Baveno VIConsensus Workshop:Stratifying risk and individualizing care for portal hypertension.J Hepatol 2015;63:743-752[PMID:26047908 DOI:10.1016/j.jhep.2015.05.022]
6 Ge PS,Runyon BA.Treatment of Patients with Cirrhosis.N Engl J Med 2016;375:767-777[PMID:27557303 DOI:10.1056/NEJMra1504367]
7 Reiberger T,Mandorfer M.Beta adrenergic blockade and decompensated cirrhosis.J Hepatol 2017;66:849-859[PMID:27864004 DOI:10.1016/j.jhep.2016.11.001]
8 Gluud LL,Morgan MY.Endoscopic therapy and beta-blockers for secondary prevention in adults with cirrhosis and oesophageal varices Cochrane Database of systematic Reviews 2017;(6):Art.No.:CD012694.[DOI:10.1002/14651858.CD012694]
9 Groszmann RJ,Bosch J,Grace ND,Conn HO,Garcia-Tsao G,Navasa M,Alberts J,Rodes J,Fischer R,Bermann M.Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage.Gastroenterology 1990;99:1401-1407[PMID:2210246 DOI:10.1016/0016-5085(90)91168-6]
10 Poynard T,Calès P,Pasta L,Ideo G,Pascal JP,Pagliaro L,Lebrec D.Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices.An analysis of data and prognostic factors in 589 patients from four randomized clinical trials.Franco-Italian Multicenter Study Group.N Engl J Med 1991;324:1532-1538[PMID:1674104 DOI:10.1056/NEJM199105303242202]
11 Lebrec D,Poynard T,Hillon P,Benhamou JP.Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis:A controlled study.N Engl J Med 1981;305:1371-1374[PMID:7029276 DOI:10.1056/NEJM198112033052302]
12 SerstéT,Melot C,Francoz C,Durand F,Rautou PE,Valla D,Moreau R,Lebrec D.Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites.Hepatology 2010;52:1017-1022[PMID:20583214 DOI:10.1002/hep.23775]
13 SerstéT,Njimi H,DegréD,Deltenre P,Schreiber J,Lepida A,Trépo E,Gustot T,Moreno C.The use of beta-blockers is associated with the occurrence of acute kidney injury in severe alcoholic hepatitis.Liver Int 2015;35:1974-1982[PMID:25611961 DOI:10.1111/liv.12786]
14 Mandorfer M,Bota S,Schwabl P,Bucsics T,Pfisterer N,Kruzik M,Hagmann M,Blacky A,Ferlitsch A,Sieghart W,Trauner M,Peck-Radosavljevic M,Reiberger T.Nonselectiveβblockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis.Gastroenterology 2014;146:1680-90.e1[PMID:24631577 DOI:10.1053/j.gastro.2014.03.005]
15 Bang UC,Benfield T,Hyldstrup L,Jensen JE,Bendtsen F.Effect of propranolol on survival in patients with decompensated cirrhosis:A nationwide study based Danish patient registers.Liver Int 2016;36:1304-1312[PMID:26992041 DOI:10.1111/liv.13119]
16 Krag A,Wiest R,Albillos A,Gluud LL.The window hypothesis:haemodynamic and non-haemodynamic effects ofβ-blockers improve survival of patients with cirrhosis during a window in the disease.Gut 2012;61:967-969[PMID:22234982 DOI:10.1136/gutjnl-2011-301348]
17 Groszmann RJ,Garcia-Tsao G,Bosch J,Grace ND,Burroughs AK,Planas R,Escorsell A,Garcia-Pagan JC,Patch D,Matloff DS,Gao H,Makuch R;Portal Hypertension Collaborative Group.Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.N Engl J Med 2005;353:2254-2261[PMID:16306522 DOI:10.1056/NEJMoa044456]
18 Villanueva C,Aracil C,Colomo A,Lopez-Balaguer JM,Piqueras M,Gonzalez B,Torras X,Guarner C,Balanzo J.Clinical trial:A randomized controlled study on prevention of variceal rebleeding comparing nadolol+ligation vs.hepatic venous pressure gradient-guided pharmacological therapy.Aliment Pharmacol Ther 2009;29:397-408[PMID:19006538 DOI:10.1111/j.1365-2036.2008.03880.x]
19 Mandorfer M,Reiberger T.Beta blockers and cirrhosis,2016.Dig Liver Dis 2017;49:3-10[PMID:27717792 DOI:10.1016/j.dld.2016.09.013]
20 Kumar A,Sharma P,Anikhindi SA,Prajapati R,Agarwal R,Sharma B,Bansal N,Singla V,Arora A.Can Non-Selective Beta-Blockers(NSBBs)Prevent Enlargement of Small Esophageal Varices in Patients with Cirrhosis?A Meta-analysis.J Clin Exp Hepatol 2017;7:275-283[PMID:29234190 DOI:10.1016/j.jceh.2017.09.003]
21 Engelmann C,Jalan R.Non selective beta-blocker in cirrhosis:Not‘whether’but‘who and how’.AMEMed J 2017;2:90[DOI:10.21037/amj.2017.06.13]
22 Kim SG,Larson JJ,Lee JS,Therneau TM,Kim WR.Beneficial and harmful effects of nonselective beta blockade on acute kidney injury in liver transplant candidates.Liver Transpl 2017;23:733-740[PMID:28187503 DOI:10.1002/lt.24744]
23 Bossen L,Krag A,Vilstrup H,Watson H,Jepsen P.Nonselectiveβ-blockers do not affect mortality in cirrhosis patients with ascites:Post Hoc analysis of three randomized controlled trials with 1198 patients.Hepatology 2016;63:1968-1976[PMID:26599983 DOI:10.1002/hep.28352]
24 Leithead JA,Rajoriya N,Tehami N,Hodson J,Gunson BK,Tripathi D,Ferguson JW.Non-selectiveβ-blockers are associated with improved survival in patients with ascites listed for liver transplantation.Gut2015;64:1111-1119[PMID:25281417 DOI:10.1136/gutjnl-2013-306502]
25 Onali S,Kalafateli M,Majumdar A,Westbrook R,O'Beirne J,Leandro G,Patch D,Tsochatzis EA.Nonselective beta-blockers are not associated with increased mortality in cirrhotic patients with ascites.Liver Int 2017;37:1334-1344[PMID:28296047 DOI:10.1111/liv.13409]
26 Facciorusso A,Roy S,Livadas S,Fevrier-Paul A,Wekesa C,Kilic ID,Chaurasia AK,Sadeq M,Muscatiello N.Nonselective Beta-Blockers Do Not Affect Survival in Cirrhotic Patients with Ascites.Dig Dis Sci 2018;63:1737-1746[PMID:29725793 DOI:10.1007/s10620-018-5092-6]
27 Njei B,Mc Carty TR,Garcia-Tsao G.Beta-blockers in patients with cirrhosis and ascites:type of betablocker matters.Gut 2016;65:1393-1394[PMID:27207973 DOI:10.1136/gutjnl-2016-312129]
28 Sinagra E,Perricone G,D'Amico M,TinèF,D'Amico G.Systematic review with meta-analysis:The haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis.Aliment Pharmacol Ther 2014;39:557-568[PMID:24461301 DOI:10.1111/apt.12634]
29 Reiberger T,Ulbrich G,Ferlitsch A,Payer BA,Schwabl P,Pinter M,Heinisch BB,Trauner M,Kramer L,Peck-Radosavljevic M;Vienna Hepatic Hemodynamic Lab.Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.Gut 2013;62:1634-1641[PMID:23250049 DOI:10.1136/gutjnl-2012-304038]
30 Sinha R,Lockman KA,Mallawaarachchi N,Robertson M,Plevris JN,Hayes PC.Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites.J Hepatol 2017;67:40-46[PMID:28213164 DOI:10.1016/j.jhep.2017.02.005]
31 Araújo Júnior RF,Garcia VB,Leit?o RF,Brito GA,Miguel Ede C,Guedes PM,de Araújo AA.Carvedilol Improves Inflammatory Response,Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells.PLo S One 2016;11:e0148868[PMID:26891124 DOI:10.1371/journal.pone.0148868]
32 Mandorfer M,Peck-Radosavljevic M,Reiberger T.Prevention of progression from small to large varices:are we there yet?An updated meta-analysis.Gut 2017;66:1347-1349[PMID:27694143 DOI:10.1136/gutjnl-2016-312814]
33 Bhardwaj A,Kedarisetty CK,Vashishtha C,Bhadoria AS,Jindal A,Kumar G,Choudhary A,Shasthry SM,Maiwall R,Kumar M,Bhatia V,Sarin SK.Carvedilol delays the progression of small oesophageal varices in patients with cirrhosis:A randomised placebo-controlled trial.Gut 2017;66:1838-1843[PMID:27298379 DOI:10.1136/gutjnl-2016-311735]
34 Zacharias AP,Jeyaraj R,Hobolth L,Bendtsen F,Gluud LL,Morgan MY.Carvedilol versus traditional,non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices.Cochrane Database Syst Rev 2018;10:CD011510[PMID:30372514 DOI:10.1002/14651858.CD011510.pub2]
35 Senzolo M,Cholongitas E,Burra P,Leandro G,Thalheimer U,Patch D,Burroughs AK.beta-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients:A meta-analysis.Liver Int 2009;29:1189-1193[PMID:19508620 DOI:10.1111/j.1478-3231.2009.02038.x]
36 Merli M,Lucidi C,Di Gregorio V,Giannelli V,Giusto M,Ceccarelli G,Riggio O,Venditti M.The chronic use of beta-blockers and proton pump inhibitors may affect the rate of bacterial infections in cirrhosis.Liver Int 2015;35:362-369[PMID:24836902 DOI:10.1111/liv.12593]
37 Mookerjee RP,Pavesi M,Thomsen KL,Mehta G,Macnaughtan J,Bendtsen F,Coenraad M,Sperl J,Gines P,Moreau R,Arroyo V,Jalan R;CANONIC Study Investigators of the EASL-CLIF Consortium.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;64:574-582[PMID:26519600 DOI:10.1016/j.jhep.2015.10.018]
38 Facciorusso A,Villani R,Bellanti F,Bruno R,Fioravanti G,Vendemiale G,Serviddio G.In-hospital mortality and length of stay in cirrhotic patients with sepsis treated with non-selective beta-blockers.Digest Liver Dis 2017;49:e15[DOI:10.1016/j.dld.2017.01.033]
39 Reiberger T,Ferlitsch A,Payer BA,Mandorfer M,Heinisch BB,Hayden H,Lammert F,Trauner M,Peck-Radosavljevic M,Vogelsang H;Vienna Hepatic Hemodynamic Lab.Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis.JHepatol 2013;58:911-921[PMID:23262249 DOI:10.1016/j.jhep.2012.12.011]
40 Pérez-Paramo M,Mu?oz J,Albillos A,Freile I,Portero F,Santos M,Ortiz-Berrocal J.Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites.Hepatology 2000;31:43-48[PMID:10613726 DOI:10.1002/hep.510310109]
41 Gimenez P,Garcia-Martinez I,Francés R,Gonzalez-Navajas JM,Mauri M,Alfayate R,Almenara S,Miralles C,Palazon JM,Carnicer F,Pascual S,Such J,Horga JF,Zapater P.Treatment with non-selective beta-blockers affects the systemic inflammatory response to bacterial DNA in patients with cirrhosis.Liver Int 2018;38:2219-2227[PMID:29802788 DOI:10.1111/liv.13890]
42 Thiele M,Albillos A,Abazi R,Wiest R,Gluud LL,Krag A.Non-selective beta-blockers may reduce risk of hepatocellular carcinoma:A meta-analysis of randomized trials.Liver Int 2015;35:2009-2016[PMID:25581713 DOI:10.1111/liv.12782]
43 Herrera I,Pascual S,Zapater P,Carnicer F,Bellot P,María Palazón J.The use ofβ-blockers is associated with a lower risk of developing hepatocellular carcinoma in patients with cirrhosis.Eur J Gastroenterol Hepatol 2016;28:1194-1197[PMID:27294486 DOI:10.1097/MEG.0000000000000677]
44 Thiele M,Wiest R,Gluud LL,Albillos A,Krag A.Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?Med Hypotheses 2013;81:871-874[PMID:24060485 DOI:10.1016/j.mehy.2013.08.026]
45 Feu F,García-Pagán JC,Bosch J,Luca A,Terés J,Escorsell A,Rodés J.Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis.Lancet1995;346:1056-1059[PMID:7564785 DOI:10.1016/S0140-6736(95)91740-3]
46 D’Amico G,Malizia G,Bosch J.Beta-blockers in 2016:Still the safest and most useful drugs for portal hypertension?Hepatology 2016;63:1771-1773[PMID:26890689 DOI:10.1002/hep.28502]
47 Peeraphatdit TB,Kamath PS,Shah VH.Beta-blockers in patients with advanced cirrhosis:Red light,green light,yellow light….Liver Transpl 2017;23:725-726[PMID:28452116 DOI:10.1002/lt.24780]
48 Garcia-Tsao G,Abraldes JG,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;65:310-335[PMID:27786365 DOI:10.1002/hep.28906]
49 European Association for the Study of the Liver.Electronic address:easloffice@easloffice.eu.;European Association for the Study of the Liver.EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis.J Hepatol 2018;69:406-460[PMID:29653741 DOI:10.1016/j.jhep.2018.03.024]
50 Conn HO,Leevy CM,Vlahcevic ZR,Rodgers JB,Maddrey WC,Seeff L,Levy LL.Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy.A double blind controlled trial.Gastroenterology 1977;72:573-583[PMID:14049]
51 Als-Nielsen B,Gluud LL,Gluud C.Non-absorbable disaccharides for hepatic encephalopathy:Systematic review of randomised trials.BMJ 2004;328:1046[PMID:15054035 DOI:10.1136/bmj.38048.506134.EE]
52 Gluud LL,Vilstrup H,Morgan MY.Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis.Cochrane Database Syst Rev 2016;4:CD003044[PMID:27089005 DOI:10.1002/14651858.CD003044.pub3]
53 Elkington SG.Lactulose.Gut 1970;11:1043-1048[PMID:4929274]
54 Sharma BC,Sharma P,Agrawal A,Sarin SK.Secondary prophylaxis of hepatic encephalopathy:An open-label randomized controlled trial of lactulose versus placebo.Gastroenterology 2009;137:885-891,891.e1[PMID:19501587 DOI:10.1053/j.gastro.2009.05.056]
55 Agrawal A,Sharma BC,Sharma P,Sarin SK.Secondary prophylaxis of hepatic encephalopathy in cirrhosis:An open-label,randomized controlled trial of lactulose,probiotics,and no therapy.Am JGastroenterol 2012;107:1043-1050[PMID:22710579 DOI:10.1038/ajg.2012.113]
56 Sharma P,Sharma BC,Agrawal A,Sarin SK.Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis:An open labeled randomized controlled trial of lactulose versus no lactulose.JGastroenterol Hepatol 2012;27:1329-1335[PMID:22606978 DOI:10.1111/j.1440-1746.2012.07186.x]
57 Prasad S,Dhiman RK,Duseja A,Chawla YK,Sharma A,Agarwal R.Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy.Hepatology 2007;45:549-559[PMID:17326150 DOI:10.1002/hep.21533]
58 Mittal VV,Sharma BC,Sharma P,Sarin SK.A randomized controlled trial comparing lactulose,probiotics,and L-ornithine L-aspartate in treatment of minimal hepatic encephalopathy.Eur JGastroenterol Hepatol 2011;23:725-732[PMID:21646910 DOI:10.1097/MEG.0b013e32834696f5]
59 Vilstrup H,Amodio P,Bajaj J,Cordoba J,Ferenci P,Mullen KD,Weissenborn K,Wong P.Hepatic encephalopathy in chronic liver disease:2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.Hepatology 2014;60:715-735[PMID:25042402 DOI:10.1002/hep.27210]
60 Iadevaia MD,Prete AD,Cesaro C,Gaeta L,Zulli C,Loguercio C.Rifaximin in the treatment of hepatic encephalopathy.Hepat Med 2011;3:109-117[PMID:24367227 DOI:10.2147/HMER.S11988]
61 Zullo A,Hassan C,Ridola L,Lorenzetti R,Campo SM,Riggio O.Rifaximin therapy and hepatic encephalopathy:Pros and cons.World J Gastrointest Pharmacol Ther 2012;3:62-67[PMID:22966484DOI:10.4292/wjgpt.v3.i4.62]
62 Mullen KD,Sanyal AJ,Bass NM,Poordad FF,Sheikh MY,Frederick RT,Bortey E,Forbes WP.Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy.Clin Gastroenterol Hepatol 2014;12:1390-7.e2[PMID:24365449 DOI:10.1016/j.cgh.2013.12.021]
63 Mas A,Rodés J,Sunyer L,Rodrigo L,Planas R,Vargas V,Castells L,Rodríguez-Martínez D,FernándezRodríguez C,Coll I,Pardo A;Spanish Association for the Study of the Liver Hepatic Encephalopathy Cooperative Group.Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy:Results of a randomized,double-blind,double-dummy,controlled clinical trial.J Hepatol 2003;38:51-58[PMID:12480560 DOI:10.1016/S0168-8278(02)00350-1]
64 Bass NM,Mullen KD,Sanyal A,Poordad F,Neff G,Leevy CB,Sigal S,Sheikh MY,Beavers K,Frederick T,Teperman L,Hillebrand D,Huang S,Merchant K,Shaw A,Bortey E,Forbes WP.Rifaximin treatment in hepatic encephalopathy.N Engl J Med 2010;362:1071-1081[PMID:20335583 DOI:10.1056/NEJMoa0907893]
65 Kimer N,Gluud LL,Morris RW,Morgan MY.Rifaximin for the prevention and treatment of hepatic encephalopathy:A systematic review with meta-analyses of randomised controlled trials.J Clin Exp Hepatol 2017;7:S78-S79[DOI:10.1016/j.jceh.2017.01.105]
66 Wu D,Wu SM,Lu J,Zhou YQ,Xu L,Guo CY.Rifaximin versus Nonabsorbable Disaccharides for the Treatment of Hepatic Encephalopathy:A Meta-Analysis.Gastroenterol Res Pract 2013;2013:236963[PMID:23653636 DOI:10.1155/2013/236963]
67 Kang SH,Lee YB,Lee JH,Nam JY,Chang Y,Cho H,Yoo JJ,Cho YY,Cho EJ,Yu SJ,Kim MY,Kim YJ,Baik SK,Yoon JH.Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.Aliment Pharmacol Ther2017;46:845-855[PMID:28836723 DOI:10.1111/apt.14275]
68 Kabeshova A,Ben Hariz S,Tsakeu E,Benamouzig R,Launois R.Cost-effectiveness analysis of rifaximin-αadministration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France.Therap Adv Gastroenterol 2016;9:473-482[PMID:27366216 DOI:10.1177/1756283X16644249]
69 Vlachogiannakos J,Viazis N,Vasianopoulou P,Vafiadis I,Karamanolis DG,Ladas SD.Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis.JGastroenterol Hepatol 2013;28:450-455[PMID:23216382 DOI:10.1111/jgh.12070]
70 Hanouneh MA,Hanouneh IA,Hashash JG,Law R,Esfeh JM,Lopez R,Hazratjee N,Smith T,Zein NN.The role of rifaximin in the primary prophylaxis of spontaneous bacterial peritonitis in patients with liver cirrhosis.J Clin Gastroenterol 2012;46:709-715[PMID:22878533 DOI:10.1097/MCG.0b013e3182506dbb]
71 Runyon BA;AASLD Practice Guidelines Committee.Management of adult patients with ascites due to cirrhosis:An update.Hepatology 2009;49:2087-2107[PMID:19475696 DOI:10.1002/hep.22853]
72 European Association for the Study of the Liver.EASL clinical practice guidelines on the management of ascites,spontaneous bacterial peritonitis,and hepatorenal syndrome in cirrhosis.J Hepatol 2010;53:397-417[PMID:20633946 DOI:10.1016/j.jhep.2010.05.004]
73 Praharaj D,Taneja S,Duseja A,Chawla Y,Dhiman RK.Randomized Control Trial of Rifaximin and Norfloxacin in Primary and Secondary Prophylaxis of Spontaneous Bacterial Peritonitis(SBP)in Cirrhotic Patients.J Clin Exp Hepatol 2017;7:S71[DOI:10.1016/j.jceh.2017.05.133]
74 Sidhu GS,Go A,Attar BM,Mutneja HR,Arora S,Patel SA.Rifaximin versus norfloxacin for prevention of spontaneous bacterial peritonitis:A systematic review.BMJ Open Gastroenterol 2017;4:e000154[PMID:28944070 DOI:10.1136/bmjgast-2017-000154]
75 Kalambokis GN,Mouzaki A,Rodi M,Pappas K,Fotopoulos A,Xourgia X,Tsianos EV.Rifaximin improves systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites.Clin Gastroenterol Hepatol 2012;10:815-818[PMID:22391344 DOI:10.1016/j.cgh.2012.02.025]
76 Baik S,Lim Y,Cho Y,Kim M,Jang Y,Suk K,Cheon G,Kim Y,Choi D.G03:Rifaximin and propranolol combination therapy is more effective than propranolol monotherapy in the hepatic venous pressure gradient response and propranolol dose reduction-A pilot study.J Hepatol 2015;62:S188[DOI:10.1016/S0168-8278(15)30004-0]
77 Kimer N,Pedersen JS,Busk TM,Gluud LL,Hobolth L,Krag A,M?ller S,Bendtsen F;Copenhagen Rifaximin(Co Rif)Study Group.Rifaximin has no effect on hemodynamics in decompensated cirrhosis:Arandomized,double-blind,placebo-controlled trial.Hepatology 2017;65:592-603[PMID:27775818 DOI:10.1002/hep.28898]
78 Nathwani R.Rifaximin to reduce infection in decompensated cirrhosis.[accessed 2017 Sep 11].In:ISRCTN registry[Internet].Available from:https://doi.org/10.1186/ISRCTN10994757 ISRCTN number:ISRCTN10994757.
79 Goh ET,Stokes CS,Sidhu SS,Vilstrup H,Gluud LL,Morgan MY.L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis.Cochrane Database Syst Rev 2018;5:CD012410[PMID:29762873 DOI:10.1002/14651858.CD012410.pub2]
80 Bai M,Yang Z,Qi X,Fan D,Han G.l-ornithine-l-aspartate for hepatic encephalopathy in patients with cirrhosis:A meta-analysis of randomized controlled trials.J Gastroenterol Hepatol 2013;28:783-792[PMID:23425108 DOI:10.1111/jgh.12142]
81 Sidhu SS.L-ornithine L-aspartate in Overt Hepatic Encephalopathy(HEAL).[accessed 2017 Aug 2].In:Clinical Trials.gov[Internet].Bethesda(MD):U.S.National Library of Medicine.Available from:https://clinicaltrials.gov/ct2/show/NCT01722578 Clinical Trials.gov Identifier:NCT01722578.L-ornithine L-aspartate in Overt Hepatic Encephalopathy(HEAL).[accessed
82 Gentile S,Guarino G,Romano M,Alagia IA,Fierro M,Annunziata S,Magliano PL,Gravina AG,Torella R.A randomized controlled trial of acarbose in hepatic encephalopathy.Clin Gastroenterol Hepatol 2005;3:184-191[PMID:15704053 DOI:10.1016/S1542-3565(04)00667-6]
83 Mullen KD,Howard R.Is acarbose an effective drug for treating patients with cirrhosis and hepatic encephalopathy?Nat Clin Pract Gastroenterol Hepatol 2005;2:264-265[PMID:16265229 DOI:10.1038/ncpgasthep0194]
84 Ventura-Cots M,Santos B,GenescàJ.α1 andα2-adrenergic agonists on cirrhotic patients with refractory ascites.Liver Int 2016;36:177-180[PMID:26284943 DOI:10.1111/liv.12941]
85 Moore KP,Aithal GP.Guidelines on the management of ascites in cirrhosis.Gut 2006;55 Suppl 6:vi1-v12[PMID:16966752 DOI:10.1136/gut.2006.099580]
86 Piano S,Tonon M,Angeli P.Management of ascites and hepatorenal syndrome.Hepatol Int 2018;12:122-134[PMID:28836115 DOI:10.1007/s12072-017-9815-0]
87 Ginès P,Cárdenas A,Arroyo V,Rodés J.Management of cirrhosis and ascites.N Engl J Med 2004;350:1646-1654[PMID:15084697 DOI:10.1056/NEJMra035021]
88 Moore KP,Wong F,Gines P,Bernardi M,Ochs A,Salerno F,Angeli P,Porayko M,Moreau R,GarciaTsao G,Jimenez W,Planas R,Arroyo V.The management of ascites in cirrhosis:Report on the consensus conference of the International Ascites Club.Hepatology 2003;38:258-266[PMID:12830009 DOI:10.1053/jhep.2003.50315]
89 Sherlock S,Walker JG,Senewiratne B,Scott A.The complications of diuretic therapy in patients with cirrhosis.Ann N Y Acad Sci 1966;139:497-505[PMID:5230290 DOI:10.1111/j.1749-6632.1966.tb41223.x]
90 Laffi G,La Villa G,Carloni V,Foschi M,Bartoletti L,Quartini M,Gentilini P.Loop diuretic therapy in liver cirrhosis with ascites.J Cardiovasc Pharmacol 1993;22 Suppl 3:S51-S58[PMID:7506337 DOI:10.1097/00005344-199322003-00007]
91 Tsochatzis EA,Gerbes AL.Diagnosis and treatment of ascites.J Hepatol 2017;67:184-185[PMID:28119010 DOI:10.1016/j.jhep.2017.01.011]
92 Senousy BE,Draganov PV.Evaluation and management of patients with refractory ascites.World JGastroenterol 2009;15:67-80[PMID:19115470 DOI:10.3748/wjg.15.67]
93 Mukerji AN,Patel V,Jain A.Improving survival in decompensated cirrhosis.Int J Hepatol 2012;2012:318627[PMID:22811919 DOI:10.1155/2012/318627]
94 Singh V,Singh A,Singh B,Vijayvergiya R,Sharma N,Ghai A,Bhalla A.Midodrine and clonidine in patients with cirrhosis and refractory or recurrent ascites:A randomized pilot study.Am J Gastroenterol2013;108:560-567[PMID:23419385 DOI:10.1038/ajg.2013.9]
95 Singh V,Dhungana SP,Singh B,Vijayverghia R,Nain CK,Sharma N,Bhalla A,Gupta PK.Midodrine in patients with cirrhosis and refractory or recurrent ascites:A randomized pilot study.J Hepatol 2012;56:348-354[PMID:21749847 DOI:10.1016/j.jhep.2011.04.027]
96 Guo TT,Yang Y,Song Y,Ren Y,Liu ZX,Cheng G.Effects of midodrine in patients with ascites due to cirrhosis:Systematic review and meta-analysis.J Dig Dis 2016;17:11-19[PMID:26630543 DOI:10.1111/1751-2980.12304]
97 Patel S,Nguyen DS,Rastogi A,Nguyen MK,Nguyen MK.Treatment of Cirrhosis-Associated Hyponatremia with Midodrine and Octreotide.Front Med(Lausanne)2017;4:17[PMID:28352627 DOI:10.3389/fmed.2017.00017]
98 Lenaerts A,Codden T,Meunier JC,Henry JP,Ligny G.Effects of clonidine on diuretic response in ascitic patients with cirrhosis and activation of sympathetic nervous system.Hepatology 2006;44:844-849[PMID:17006921 DOI:10.1002/hep.21355]
99 SansoèG,Aragno M,Mastrocola R,Parola M.Dose-dependency of clonidine's effects in ascitic cirrhotic rats:Comparison withα1-adrenergic agonist midodrine.Liver Int 2016;36:205-211[PMID:26121993DOI:10.1111/liv.12905]
100 Yan L,Xie F,Lu J,Ni Q,Shi C,Tang C,Yang J.The treatment of vasopressin V2-receptor antagonists in cirrhosis patients with ascites:A meta-analysis of randomized controlled trials.BMC Gastroenterol 2015;15:65[PMID:26054761 DOI:10.1186/s12876-015-0297-z]
101 Pose E,Cardenas A.Translating Our Current Understanding of Ascites Management into New Therapies for Patients with Cirrhosis and Fluid Retention.Dig Dis 2017;35:402-410[PMID:28468013 DOI:10.1159/000456595]
102 Wong F,Watson H,Gerbes A,Vilstrup H,Badalamenti S,Bernardi M,Ginès P;Satavaptan Investigators Group.Satavaptan for the management of ascites in cirrhosis:Efficacy and safety across the spectrum of ascites severity.Gut 2012;61:108-116[PMID:21836029 DOI:10.1136/gutjnl-2011-300157]
103 Vargas JI,Arrese M,Shah VH,Arab JP.Use of Statins in Patients with Chronic Liver Disease and Cirrhosis:Current Views and Prospects.Curr Gastroenterol Rep 2017;19:43[PMID:28752475 DOI:10.1007/s11894-017-0584-7]
104 Cabrera L,Abraldes JG.Statins:The Panacea of Cirrhosis?Curr Hepatol Rep 2016;15:1-7[DOI:10.1007/s11901-016-0287-9]
105 Zafra C,Abraldes JG,Turnes J,Berzigotti A,Fernández M,Garca-Pagán JC,Rodés J,Bosch J.Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis.Gastroenterology 2004;126:749-755[PMID:14988829 DOI:10.1053/j.gastro.2003.12.007]
106 Abraldes JG,Albillos A,Ba?ares R,Turnes J,González R,García-Pagán JC,Bosch J.Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension:A randomized controlled trial.Gastroenterology 2009;136:1651-1658[PMID:19208350 DOI:10.1053/j.gastro.2009.01.043]
107 Kumar S,Grace ND,Qamar AA.Statin use in patients with cirrhosis:A retrospective cohort study.Dig Dis Sci 2014;59:1958-1965[PMID:24838495 DOI:10.1007/s10620-014-3179-2]
108 Mohanty A,Tate JP,Garcia-Tsao G.Statins Are Associated With a Decreased Risk of Decompensation and Death in Veterans With Hepatitis C-Related Compensated Cirrhosis.Gastroenterology 2016;150:430-40.e1[PMID:26484707 DOI:10.1053/j.gastro.2015.10.007]
109 Chang FM,Wang YP,Lang HC,Tsai CF,Hou MC,Lee FY,Lu CL.Statins decrease the risk of decompensation in hepatitis B virus-and hepatitis C virus-related cirrhosis:A population-based study.Hepatology 2017;66:896-907[PMID:28318053 DOI:10.1002/hep.29172]
110 Abraldes JG,Villanueva C,Aracil C,Turnes J,Hernandez-Guerra M,Genesca J,Rodriguez M,Castellote J,García-Pagán JC,Torres F,Calleja JL,Albillos A,Bosch J;BLEPS Study Group.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;150:1160-1170.e3[PMID:26774179 DOI:10.1053/j.gastro.2016.01.004]
111 Kamal S,Khan MA,Seth A,Cholankeril G,Gupta D,Singh U,Kamal F,Howden CW,Stave C,Nair S,Satapathy SK,Ahmed A.Beneficial Effects of Statins on the Rates of Hepatic Fibrosis,Hepatic Decompensation,and Mortality in Chronic Liver Disease:A Systematic Review and Meta-Analysis.Am JGastroenterol 2017;112:1495-1505[PMID:28585556 DOI:10.1038/ajg.2017.170]
112 Kim RG,Loomba R,Prokop LJ,Singh S.Statin Use and Risk of Cirrhosis and Related Complications in Patients With Chronic Liver Diseases:A Systematic Review and Meta-analysis.Clin Gastroenterol Hepatol 2017;15:1521-1530.e8[PMID:28479502 DOI:10.1016/j.cgh.2017.04.039]
113 Singh S,Singh PP,Singh AG,Murad MH,Sanchez W.Statins are associated with a reduced risk of hepatocellular cancer:A systematic review and meta-analysis.Gastroenterology 2013;144:323-332[PMID:23063971 DOI:10.1053/j.gastro.2012.10.005]
114 Tsochatzis EA,Bosch J.Statins in cirrhosis-Ready for prime time.Hepatology 2017;66:697-699[PMID:28543643 DOI:10.1002/hep.29277]
115 Chalasani N,Aljadhey H,Kesterson J,Murray MD,Hall SD.Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity.Gastroenterology 2004;126:1287-1292[PMID:15131789 DOI:10.1053/j.gastro.2004.02.015]
116 Lewis JH,Mortensen ME,Zweig S,Fusco MJ,Medoff JR,Belder R;Pravastatin in Chronic Liver Disease Study Investigators.Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease:Results of a prospective,randomized,double-blind,placebocontrolled,multicenter trial.Hepatology 2007;46:1453-1463[PMID:17668878 DOI:10.1002/hep.21848]
117 Chalasani N,Younossi Z,Lavine JE,Charlton M,Cusi K,Rinella M,Harrison SA,Brunt EM,Sanyal AJ.The diagnosis and management of nonalcoholic fatty liver disease:Practice guidance from the American Association for the Study of Liver Diseases.Hepatology 2018;67:328-357[PMID:28714183 DOI:10.1002/hep.29367]
118 European Association for the Study of the Liver(EASL).;European Association for the Study of Diabetes(EASD);European Association for the Study of Obesity(EASO).EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease.Obes Facts 2016;9:65-90[PMID:27055256 DOI:10.1159/000443344]
119 Moctezuma-Velázquez C,Abraldes JG,Montano-Loza AJ.The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis.Curr Treat Options Gastroenterol 2018;16:226-240[PMID:29572618 DOI:10.1007/s11938-018-0180-4]
120 Lodato F,Azzaroli F,Di Girolamo M,Feletti V,Cecinato P,Lisotti A,Festi D,Roda E,Mazzella G.Proton pump inhibitors in cirrhosis:Tradition or evidence based practice?World J Gastroenterol 2008;14:2980-2985[PMID:18494046 DOI:10.3748/wjg.14.2980]
121 Dam G,Vilstrup H,Watson H,Jepsen P.Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites.Hepatology2016;64:1265-1272[PMID:27474889 DOI:10.1002/hep.28737]
122 Dultz G,Piiper A,Zeuzem S,Kronenberger B,Waidmann O.Proton pump inhibitor treatment is associated with the severity of liver disease and increased mortality in patients with cirrhosis.Aliment Pharmacol Ther 2015;41:459-466[PMID:25523381 DOI:10.1111/apt.13061]
123 Trikudanathan G,Israel J,Cappa J,O'Sullivan DM.Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients-a systematic review and meta-analysis.Int J Clin Pract 2011;65:674-678[PMID:21564440 DOI:10.1111/j.1742-1241.2011.02650.x]
124 Khan MA,Cholankeril G,Howden CW.Are proton pump inhibitors a threat for spontaneous bacterial peritonitis and hepatic encephalopathy in cirrhosis?Not so fast.Hepatology 2017;65:393[PMID:27688049 DOI:10.1002/hep.28858]
125 Tsai CF,Chen MH,Wang YP,Chu CJ,Huang YH,Lin HC,Hou MC,Lee FY,Su TP,Lu CL.Proton Pump Inhibitors Increase Risk for Hepatic Encephalopathy in Patients With Cirrhosis in A Population Study.Gastroenterology 2017;152:134-141[PMID:27639806 DOI:10.1053/j.gastro.2016.09.007]
126 Woodhouse CA,Patel VC,Singanayagam A,Shawcross DL.Review article:the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.Aliment Pharmacol Ther2018;47:192-202[PMID:29083037 DOI:10.1111/apt.14397]
127 Bajaj JS,Acharya C,Fagan A,White MB,Gavis E,Heuman DM,Hylemon PB,Fuchs M,Puri P,Schubert ML,Sanyal AJ,Sterling RK,Stravitz RT,Siddiqui MS,Luketic V,Lee H,Sikaroodi M,Gillevet PM.Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis.Am J Gastroenterol 2018;113:1177-1186[PMID:29872220 DOI:10.1038/s41395-018-0085-9]
128 Ratuapli SK,Ellington TG,O'Neill MT,Umar SB,Harris LA,Foxx-Orenstein AE,Burdick GE,Dibaise JK,Lacy BE,Crowell MD.Proton pump inhibitor therapy use does not predispose to small intestinal bacterial overgrowth.Am J Gastroenterol 2012;107:730-735[PMID:22334250 DOI:10.1038/ajg.2012.4]
129 Assaraf J,Weiss N,Thabut D.Proton Pump Inhibitor Administration Triggers Encephalopathy in Cirrhotic Patients by Modulating Blood-Brain Barrier Drug Transport.Gastroenterology 2017;152:2077[PMID:28478148 DOI:10.1053/j.gastro.2016.10.049]
130 Khan MA,Cholankeril G,Howden CW.Proton Pump Inhibitors and the Possible Development of Hepatic Encephalopathy in Cirrhotic Patients:True Association or Residual Confounding?Gastroenterology 2017;152:2076[PMID:28478154 DOI:10.1053/j.gastro.2016.10.050]
131 Terg R,Casciato P,Garbe C,Cartier M,Stieben T,Mendizabal M,Niveyro C,Benavides J,Marino M,Colombato L,Berbara D,Silva M,Salgado P,Barreyro F,Fassio E,Gadano A;Study Group of Cirrhosis Complications of the Argentine Association for the Study of Liver Disease.Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis:A multicenter prospective study.J Hepatol 2015;62:1056-1060[PMID:25481567 DOI:10.1016/j.jhep.2014.11.036]
132 Yu T,Tang Y,Jiang L,Zheng Y,Xiong W,Lin L.Proton pump inhibitor therapy and its association with spontaneous bacterial peritonitis incidence and mortality:A meta-analysis.Dig Liver Dis 2016;48:353-359[PMID:26795544 DOI:10.1016/j.dld.2015.12.009]
133 Dhar A,Mullish BH,Thursz MR.Anticoagulation in chronic liver disease.J Hepatol 2017;66:1313-1326[PMID:28088580 DOI:10.1016/j.jhep.2017.01.006]
134 Leonardi F,Maria N,Villa E.Anticoagulation in cirrhosis:A new paradigm?Clin Mol Hepatol 2017;23:13-21[PMID:28288507 DOI:10.3350/cmh.2016.0110]
135 Bitto N,Liguori E,La Mura V.Coagulation,Microenvironment and Liver Fibrosis.Cells 2018;7:pii:E85[PMID:30042349 DOI:10.3390/cells7080085]
136 Dabbagh O,Oza A,Prakash S,Sunna R,Saettele TM.Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease.Chest 2010;137:1145-1149[PMID:20040609 DOI:10.1378/chest.09-2177]
137 Villa E,CammàC,Marietta M,Luongo M,Critelli R,Colopi S,Tata C,Zecchini R,Gitto S,Petta S,Lei B,Bernabucci V,Vukotic R,De Maria N,Schepis F,Karampatou A,Caporali C,Simoni L,Del Buono M,Zambotto B,Turola E,Fornaciari G,Schianchi S,Ferrari A,Valla D.Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis.Gastroenterology 2012;143:1253-1260.e4[PMID:22819864 DOI:10.1053/j.gastro.2012.07.018]
138 Senzolo M,M Sartori T,Rossetto V,Burra P,Cillo U,Boccagni P,Gasparini D,Miotto D,Simioni P,Tsochatzis E,A Burroughs K.Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis.Liver Int 2012;32:919-927[PMID:22435854 DOI:10.1111/j.1478-3231.2012.02785.x]
139 Chen H,Liu L,Qi X,He C,Wu F,Fan D,Han G.Efficacy and safety of anticoagulation in more advanced portal vein thrombosis in patients with liver cirrhosis.Eur J Gastroenterol Hepatol 2016;28:82-89[PMID:26513611 DOI:10.1097/MEG.0000000000000482]
140 Delgado MG,Seijo S,Yepes I,Achécar L,Catalina MV,García-Criado A,Abraldes JG,de la Pe?a J,Ba?ares R,Albillos A,Bosch J,García-Pagán JC.Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis.Clin Gastroenterol Hepatol 2012;10:776-783[PMID:22289875DOI:10.1016/j.cgh.2012.01.012]
141 Amitrano L,Guardascione MA,Menchise A,Martino R,Scaglione M,Giovine S,Romano L,Balzano A.Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis.J Clin Gastroenterol 2010;44:448-451[PMID:19730112DOI:10.1097/MCG.0b013e3181b3ab44]
142 Bernardi M,Maggioli C,Zaccherini G.Human albumin in the management of complications of liver cirrhosis.Crit Care 2012;16:211[PMID:22429536]
143 Arroyo V,García-Martinez R,Salvatella X.Human serum albumin,systemic inflammation,and cirrhosis.J Hepatol 2014;61:396-407[PMID:24751830 DOI:10.1016/j.jhep.2014.04.012]
144 Garcia-Martinez R,Caraceni P,Bernardi M,Gines P,Arroyo V,Jalan R.Albumin:Pathophysiologic basis of its role in the treatment of cirrhosis and its complications.Hepatology 2013;58:1836-1846[PMID:23423799 DOI:10.1002/hep.26338]
145 Salerno F,Navickis RJ,Wilkes MM.Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis:A meta-analysis of randomized trials.Clin Gastroenterol Hepatol 2013;11:123-30.e1[PMID:23178229 DOI:10.1016/j.cgh.2012.11.007]
146 Sanyal AJ,Boyer T,Garcia-Tsao G,Regenstein F,Rossaro L,Appenrodt B,Blei A,Gülberg V,Sigal S,Teuber P;Terlipressin Study Group.A randomized,prospective,double-blind,placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome.Gastroenterology 2008;134:1360-1368[PMID:18471513DOI:10.1053/j.gastro.2008.02.014]
147 Bernardi M,Caraceni P,Navickis RJ,Wilkes MM.Albumin infusion in patients undergoing largevolume paracentesis:A meta-analysis of randomized trials.Hepatology 2012;55:1172-1181[PMID:22095893 DOI:10.1002/hep.24786]
148 Caraceni P,Riggio O,Angeli P,Alessandria C,Neri S,Foschi FG,Levantesi F,Airoldi A,Boccia S,Svegliati-Baroni G,Fagiuoli S,Romanelli RG,Cozzolongo R,Di Marco V,Sangiovanni V,Morisco F,Toniutto P,Tortora A,De Marco R,Angelico M,Cacciola I,Elia G,Federico A,Massironi S,Guarisco R,Galioto A,Ballardini G,Rendina M,Nardelli S,Piano S,Elia C,Prestianni L,Cappa FM,Cesarini L,Simone L,Pasquale C,Cavallin M,Andrealli A,Fidone F,Ruggeri M,Roncadori A,Baldassarre M,Tufoni M,Zaccherini G,Bernardi M;ANSWER Study Investigators.Long-term albumin administration in decompensated cirrhosis(ANSWER):An open-label randomised trial.Lancet 2018;391:2417-2429[PMID:29861076 DOI:10.1016/S0140-6736(18)30840-7]
149 Mullish BH,Quraishi MN,Segal JP,Mc Cune VL,Baxter M,Marsden GL,Moore DJ,Colville A,Bhala N,Iqbal TH,Settle C,Kontkowski G,Hart AL,Hawkey PM,Goldenberg SD,Williams HRT.The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications:Joint British Society of Gastroenterology(BSG)and Healthcare Infection Society(HIS)guidelines.Gut 2018;67:1920-1941[PMID:30154172 DOI:10.1136/gutjnl-2018-316818]
150 Bajaj JS,Kassam Z,Fagan A,Gavis EA,Liu E,Cox IJ,Kheradman R,Heuman D,Wang J,Gurry T,Williams R,Sikaroodi M,Fuchs M,Alm E,John B,Thacker LR,Riva A,Smith M,Taylor-Robinson SD,Gillevet PM.Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy:Arandomized clinical trial.Hepatology 2017;66:1727-1738[PMID:28586116 DOI:10.1002/hep.29306]
151 Woodhouse C.Trial of faecal microbiota transplantation in cirrhosis.ISRCTN registry.[accessed 2018May 21].In:ISRCTN registry[Internet].Available from:https://doi.org/10.1186/ISRCTN11814003ISRCTN number:ISRCTN11814003.
152 Dranoff JA.Coffee Consumption and Prevention of Cirrhosis:In Support of the Caffeine Hypothesis.Gene Expr 2018;18:1-3[PMID:28893365 DOI:10.3727/105221617X15046391179559]
153 Salomone F,Galvano F,Li Volti G.Molecular Bases Underlying the Hepatoprotective Effects of Coffee.Nutrients 2017;9:pii:E85[PMID:28124992 DOI:10.3390/nu9010085]
154 Petta S,Marchesini G.Coffee and tea breaks for liver health.J Hepatol 2017;67:221-223[PMID:28578838 DOI:10.1016/j.jhep.2017.04.014]
155 Corrao G,Zambon A,Bagnardi V,D'Amicis A,Klatsky A;Collaborative SIDECIR Group.Coffee,caffeine,and the risk of liver cirrhosis.Ann Epidemiol 2001;11:458-465[PMID:11557177 DOI:10.1016/S1047-2797(01)00223-X]
156 Alferink LJM,Fittipaldi J,Kiefte-de Jong JC,Taimr P,Hansen BE,Metselaar HJ,Schoufour JD,Ikram MA,Janssen HLA,Franco OH,Darwish Murad S.Coffee and herbal tea consumption is associated with lower liver stiffness in the general population:The Rotterdam study.J Hepatol 2017;67:339-348[PMID:28578837 DOI:10.1016/j.jhep.2017.03.013]
157 Yu C,Cao Q,Chen P,Yang S,Deng M,Wang Y,Li L.An updated dose-response meta-analysis of coffee consumption and liver cancer risk.Sci Rep 2016;6:37488[PMID:27910873 DOI:10.1038/srep37488]
158 Freedman ND,Everhart JE,Lindsay KL,Ghany MG,Curto TM,Shiffman ML,Lee WM,Lok AS,Di Bisceglie AM,Bonkovsky HL,Hoefs JC,Dienstag JL,Morishima C,Abnet CC,Sinha R;HALT-C Trial Group.Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C.Hepatology 2009;50:1360-1369[PMID:19676128 DOI:10.1002/hep.23162]
2 Blachier M,Leleu H,Peck-Radosavljevic M,Valla DC,Roudot-Thoraval F.The burden of liver disease in Europe:A review of available epidemiological data.J Hepatol 2013;58:593-608[PMID:23419824DOI:10.1016/j.jhep.2012.12.005]
3 Williams R,Aspinall R,Bellis M,Camps-Walsh G,Cramp M,Dhawan A,Ferguson J,Forton D,Foster G,Gilmore I,Hickman M,Hudson M,Kelly D,Langford A,Lombard M,Longworth L,Martin N,Moriarty K,Newsome P,O'Grady J,Pryke R,Rutter H,Ryder S,Sheron N,Smith T.Addressing liver disease in the UK:A blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol,obesity,and viral hepatitis.Lancet 2014;384:1953-1997[PMID:25433429 DOI:10.1016/S0140-6736(14)61838-9]
4 Moctezuma-Velazquez C,Kalainy S,Abraldes JG.Beta-blockers in patients with advanced liver disease:Has the dust settled?Liver Transpl 2017;23:1058-1069[PMID:28590564 DOI:10.1002/lt.24794]
5 de Franchis R;Baveno VI Faculty.Expanding consensus in portal hypertension:Report of the Baveno VIConsensus Workshop:Stratifying risk and individualizing care for portal hypertension.J Hepatol 2015;63:743-752[PMID:26047908 DOI:10.1016/j.jhep.2015.05.022]
6 Ge PS,Runyon BA.Treatment of Patients with Cirrhosis.N Engl J Med 2016;375:767-777[PMID:27557303 DOI:10.1056/NEJMra1504367]
7 Reiberger T,Mandorfer M.Beta adrenergic blockade and decompensated cirrhosis.J Hepatol 2017;66:849-859[PMID:27864004 DOI:10.1016/j.jhep.2016.11.001]
8 Gluud LL,Morgan MY.Endoscopic therapy and beta-blockers for secondary prevention in adults with cirrhosis and oesophageal varices Cochrane Database of systematic Reviews 2017;(6):Art.No.:CD012694.[DOI:10.1002/14651858.CD012694]
9 Groszmann RJ,Bosch J,Grace ND,Conn HO,Garcia-Tsao G,Navasa M,Alberts J,Rodes J,Fischer R,Bermann M.Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage.Gastroenterology 1990;99:1401-1407[PMID:2210246 DOI:10.1016/0016-5085(90)91168-6]
10 Poynard T,Calès P,Pasta L,Ideo G,Pascal JP,Pagliaro L,Lebrec D.Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices.An analysis of data and prognostic factors in 589 patients from four randomized clinical trials.Franco-Italian Multicenter Study Group.N Engl J Med 1991;324:1532-1538[PMID:1674104 DOI:10.1056/NEJM199105303242202]
11 Lebrec D,Poynard T,Hillon P,Benhamou JP.Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis:A controlled study.N Engl J Med 1981;305:1371-1374[PMID:7029276 DOI:10.1056/NEJM198112033052302]
12 SerstéT,Melot C,Francoz C,Durand F,Rautou PE,Valla D,Moreau R,Lebrec D.Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites.Hepatology 2010;52:1017-1022[PMID:20583214 DOI:10.1002/hep.23775]
13 SerstéT,Njimi H,DegréD,Deltenre P,Schreiber J,Lepida A,Trépo E,Gustot T,Moreno C.The use of beta-blockers is associated with the occurrence of acute kidney injury in severe alcoholic hepatitis.Liver Int 2015;35:1974-1982[PMID:25611961 DOI:10.1111/liv.12786]
14 Mandorfer M,Bota S,Schwabl P,Bucsics T,Pfisterer N,Kruzik M,Hagmann M,Blacky A,Ferlitsch A,Sieghart W,Trauner M,Peck-Radosavljevic M,Reiberger T.Nonselectiveβblockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis.Gastroenterology 2014;146:1680-90.e1[PMID:24631577 DOI:10.1053/j.gastro.2014.03.005]
15 Bang UC,Benfield T,Hyldstrup L,Jensen JE,Bendtsen F.Effect of propranolol on survival in patients with decompensated cirrhosis:A nationwide study based Danish patient registers.Liver Int 2016;36:1304-1312[PMID:26992041 DOI:10.1111/liv.13119]
16 Krag A,Wiest R,Albillos A,Gluud LL.The window hypothesis:haemodynamic and non-haemodynamic effects ofβ-blockers improve survival of patients with cirrhosis during a window in the disease.Gut 2012;61:967-969[PMID:22234982 DOI:10.1136/gutjnl-2011-301348]
17 Groszmann RJ,Garcia-Tsao G,Bosch J,Grace ND,Burroughs AK,Planas R,Escorsell A,Garcia-Pagan JC,Patch D,Matloff DS,Gao H,Makuch R;Portal Hypertension Collaborative Group.Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.N Engl J Med 2005;353:2254-2261[PMID:16306522 DOI:10.1056/NEJMoa044456]
18 Villanueva C,Aracil C,Colomo A,Lopez-Balaguer JM,Piqueras M,Gonzalez B,Torras X,Guarner C,Balanzo J.Clinical trial:A randomized controlled study on prevention of variceal rebleeding comparing nadolol+ligation vs.hepatic venous pressure gradient-guided pharmacological therapy.Aliment Pharmacol Ther 2009;29:397-408[PMID:19006538 DOI:10.1111/j.1365-2036.2008.03880.x]
19 Mandorfer M,Reiberger T.Beta blockers and cirrhosis,2016.Dig Liver Dis 2017;49:3-10[PMID:27717792 DOI:10.1016/j.dld.2016.09.013]
20 Kumar A,Sharma P,Anikhindi SA,Prajapati R,Agarwal R,Sharma B,Bansal N,Singla V,Arora A.Can Non-Selective Beta-Blockers(NSBBs)Prevent Enlargement of Small Esophageal Varices in Patients with Cirrhosis?A Meta-analysis.J Clin Exp Hepatol 2017;7:275-283[PMID:29234190 DOI:10.1016/j.jceh.2017.09.003]
21 Engelmann C,Jalan R.Non selective beta-blocker in cirrhosis:Not‘whether’but‘who and how’.AMEMed J 2017;2:90[DOI:10.21037/amj.2017.06.13]
22 Kim SG,Larson JJ,Lee JS,Therneau TM,Kim WR.Beneficial and harmful effects of nonselective beta blockade on acute kidney injury in liver transplant candidates.Liver Transpl 2017;23:733-740[PMID:28187503 DOI:10.1002/lt.24744]
23 Bossen L,Krag A,Vilstrup H,Watson H,Jepsen P.Nonselectiveβ-blockers do not affect mortality in cirrhosis patients with ascites:Post Hoc analysis of three randomized controlled trials with 1198 patients.Hepatology 2016;63:1968-1976[PMID:26599983 DOI:10.1002/hep.28352]
24 Leithead JA,Rajoriya N,Tehami N,Hodson J,Gunson BK,Tripathi D,Ferguson JW.Non-selectiveβ-blockers are associated with improved survival in patients with ascites listed for liver transplantation.Gut2015;64:1111-1119[PMID:25281417 DOI:10.1136/gutjnl-2013-306502]
25 Onali S,Kalafateli M,Majumdar A,Westbrook R,O'Beirne J,Leandro G,Patch D,Tsochatzis EA.Nonselective beta-blockers are not associated with increased mortality in cirrhotic patients with ascites.Liver Int 2017;37:1334-1344[PMID:28296047 DOI:10.1111/liv.13409]
26 Facciorusso A,Roy S,Livadas S,Fevrier-Paul A,Wekesa C,Kilic ID,Chaurasia AK,Sadeq M,Muscatiello N.Nonselective Beta-Blockers Do Not Affect Survival in Cirrhotic Patients with Ascites.Dig Dis Sci 2018;63:1737-1746[PMID:29725793 DOI:10.1007/s10620-018-5092-6]
27 Njei B,Mc Carty TR,Garcia-Tsao G.Beta-blockers in patients with cirrhosis and ascites:type of betablocker matters.Gut 2016;65:1393-1394[PMID:27207973 DOI:10.1136/gutjnl-2016-312129]
28 Sinagra E,Perricone G,D'Amico M,TinèF,D'Amico G.Systematic review with meta-analysis:The haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis.Aliment Pharmacol Ther 2014;39:557-568[PMID:24461301 DOI:10.1111/apt.12634]
29 Reiberger T,Ulbrich G,Ferlitsch A,Payer BA,Schwabl P,Pinter M,Heinisch BB,Trauner M,Kramer L,Peck-Radosavljevic M;Vienna Hepatic Hemodynamic Lab.Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.Gut 2013;62:1634-1641[PMID:23250049 DOI:10.1136/gutjnl-2012-304038]
30 Sinha R,Lockman KA,Mallawaarachchi N,Robertson M,Plevris JN,Hayes PC.Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites.J Hepatol 2017;67:40-46[PMID:28213164 DOI:10.1016/j.jhep.2017.02.005]
31 Araújo Júnior RF,Garcia VB,Leit?o RF,Brito GA,Miguel Ede C,Guedes PM,de Araújo AA.Carvedilol Improves Inflammatory Response,Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells.PLo S One 2016;11:e0148868[PMID:26891124 DOI:10.1371/journal.pone.0148868]
32 Mandorfer M,Peck-Radosavljevic M,Reiberger T.Prevention of progression from small to large varices:are we there yet?An updated meta-analysis.Gut 2017;66:1347-1349[PMID:27694143 DOI:10.1136/gutjnl-2016-312814]
33 Bhardwaj A,Kedarisetty CK,Vashishtha C,Bhadoria AS,Jindal A,Kumar G,Choudhary A,Shasthry SM,Maiwall R,Kumar M,Bhatia V,Sarin SK.Carvedilol delays the progression of small oesophageal varices in patients with cirrhosis:A randomised placebo-controlled trial.Gut 2017;66:1838-1843[PMID:27298379 DOI:10.1136/gutjnl-2016-311735]
34 Zacharias AP,Jeyaraj R,Hobolth L,Bendtsen F,Gluud LL,Morgan MY.Carvedilol versus traditional,non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices.Cochrane Database Syst Rev 2018;10:CD011510[PMID:30372514 DOI:10.1002/14651858.CD011510.pub2]
35 Senzolo M,Cholongitas E,Burra P,Leandro G,Thalheimer U,Patch D,Burroughs AK.beta-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients:A meta-analysis.Liver Int 2009;29:1189-1193[PMID:19508620 DOI:10.1111/j.1478-3231.2009.02038.x]
36 Merli M,Lucidi C,Di Gregorio V,Giannelli V,Giusto M,Ceccarelli G,Riggio O,Venditti M.The chronic use of beta-blockers and proton pump inhibitors may affect the rate of bacterial infections in cirrhosis.Liver Int 2015;35:362-369[PMID:24836902 DOI:10.1111/liv.12593]
37 Mookerjee RP,Pavesi M,Thomsen KL,Mehta G,Macnaughtan J,Bendtsen F,Coenraad M,Sperl J,Gines P,Moreau R,Arroyo V,Jalan R;CANONIC Study Investigators of the EASL-CLIF Consortium.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;64:574-582[PMID:26519600 DOI:10.1016/j.jhep.2015.10.018]
38 Facciorusso A,Villani R,Bellanti F,Bruno R,Fioravanti G,Vendemiale G,Serviddio G.In-hospital mortality and length of stay in cirrhotic patients with sepsis treated with non-selective beta-blockers.Digest Liver Dis 2017;49:e15[DOI:10.1016/j.dld.2017.01.033]
39 Reiberger T,Ferlitsch A,Payer BA,Mandorfer M,Heinisch BB,Hayden H,Lammert F,Trauner M,Peck-Radosavljevic M,Vogelsang H;Vienna Hepatic Hemodynamic Lab.Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis.JHepatol 2013;58:911-921[PMID:23262249 DOI:10.1016/j.jhep.2012.12.011]
40 Pérez-Paramo M,Mu?oz J,Albillos A,Freile I,Portero F,Santos M,Ortiz-Berrocal J.Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites.Hepatology 2000;31:43-48[PMID:10613726 DOI:10.1002/hep.510310109]
41 Gimenez P,Garcia-Martinez I,Francés R,Gonzalez-Navajas JM,Mauri M,Alfayate R,Almenara S,Miralles C,Palazon JM,Carnicer F,Pascual S,Such J,Horga JF,Zapater P.Treatment with non-selective beta-blockers affects the systemic inflammatory response to bacterial DNA in patients with cirrhosis.Liver Int 2018;38:2219-2227[PMID:29802788 DOI:10.1111/liv.13890]
42 Thiele M,Albillos A,Abazi R,Wiest R,Gluud LL,Krag A.Non-selective beta-blockers may reduce risk of hepatocellular carcinoma:A meta-analysis of randomized trials.Liver Int 2015;35:2009-2016[PMID:25581713 DOI:10.1111/liv.12782]
43 Herrera I,Pascual S,Zapater P,Carnicer F,Bellot P,María Palazón J.The use ofβ-blockers is associated with a lower risk of developing hepatocellular carcinoma in patients with cirrhosis.Eur J Gastroenterol Hepatol 2016;28:1194-1197[PMID:27294486 DOI:10.1097/MEG.0000000000000677]
44 Thiele M,Wiest R,Gluud LL,Albillos A,Krag A.Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?Med Hypotheses 2013;81:871-874[PMID:24060485 DOI:10.1016/j.mehy.2013.08.026]
45 Feu F,García-Pagán JC,Bosch J,Luca A,Terés J,Escorsell A,Rodés J.Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis.Lancet1995;346:1056-1059[PMID:7564785 DOI:10.1016/S0140-6736(95)91740-3]
46 D’Amico G,Malizia G,Bosch J.Beta-blockers in 2016:Still the safest and most useful drugs for portal hypertension?Hepatology 2016;63:1771-1773[PMID:26890689 DOI:10.1002/hep.28502]
47 Peeraphatdit TB,Kamath PS,Shah VH.Beta-blockers in patients with advanced cirrhosis:Red light,green light,yellow light….Liver Transpl 2017;23:725-726[PMID:28452116 DOI:10.1002/lt.24780]
48 Garcia-Tsao G,Abraldes JG,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;65:310-335[PMID:27786365 DOI:10.1002/hep.28906]
49 European Association for the Study of the Liver.Electronic address:easloffice@easloffice.eu.;European Association for the Study of the Liver.EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis.J Hepatol 2018;69:406-460[PMID:29653741 DOI:10.1016/j.jhep.2018.03.024]
50 Conn HO,Leevy CM,Vlahcevic ZR,Rodgers JB,Maddrey WC,Seeff L,Levy LL.Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy.A double blind controlled trial.Gastroenterology 1977;72:573-583[PMID:14049]
51 Als-Nielsen B,Gluud LL,Gluud C.Non-absorbable disaccharides for hepatic encephalopathy:Systematic review of randomised trials.BMJ 2004;328:1046[PMID:15054035 DOI:10.1136/bmj.38048.506134.EE]
52 Gluud LL,Vilstrup H,Morgan MY.Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis.Cochrane Database Syst Rev 2016;4:CD003044[PMID:27089005 DOI:10.1002/14651858.CD003044.pub3]
53 Elkington SG.Lactulose.Gut 1970;11:1043-1048[PMID:4929274]
54 Sharma BC,Sharma P,Agrawal A,Sarin SK.Secondary prophylaxis of hepatic encephalopathy:An open-label randomized controlled trial of lactulose versus placebo.Gastroenterology 2009;137:885-891,891.e1[PMID:19501587 DOI:10.1053/j.gastro.2009.05.056]
55 Agrawal A,Sharma BC,Sharma P,Sarin SK.Secondary prophylaxis of hepatic encephalopathy in cirrhosis:An open-label,randomized controlled trial of lactulose,probiotics,and no therapy.Am JGastroenterol 2012;107:1043-1050[PMID:22710579 DOI:10.1038/ajg.2012.113]
56 Sharma P,Sharma BC,Agrawal A,Sarin SK.Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis:An open labeled randomized controlled trial of lactulose versus no lactulose.JGastroenterol Hepatol 2012;27:1329-1335[PMID:22606978 DOI:10.1111/j.1440-1746.2012.07186.x]
57 Prasad S,Dhiman RK,Duseja A,Chawla YK,Sharma A,Agarwal R.Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy.Hepatology 2007;45:549-559[PMID:17326150 DOI:10.1002/hep.21533]
58 Mittal VV,Sharma BC,Sharma P,Sarin SK.A randomized controlled trial comparing lactulose,probiotics,and L-ornithine L-aspartate in treatment of minimal hepatic encephalopathy.Eur JGastroenterol Hepatol 2011;23:725-732[PMID:21646910 DOI:10.1097/MEG.0b013e32834696f5]
59 Vilstrup H,Amodio P,Bajaj J,Cordoba J,Ferenci P,Mullen KD,Weissenborn K,Wong P.Hepatic encephalopathy in chronic liver disease:2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.Hepatology 2014;60:715-735[PMID:25042402 DOI:10.1002/hep.27210]
60 Iadevaia MD,Prete AD,Cesaro C,Gaeta L,Zulli C,Loguercio C.Rifaximin in the treatment of hepatic encephalopathy.Hepat Med 2011;3:109-117[PMID:24367227 DOI:10.2147/HMER.S11988]
61 Zullo A,Hassan C,Ridola L,Lorenzetti R,Campo SM,Riggio O.Rifaximin therapy and hepatic encephalopathy:Pros and cons.World J Gastrointest Pharmacol Ther 2012;3:62-67[PMID:22966484DOI:10.4292/wjgpt.v3.i4.62]
62 Mullen KD,Sanyal AJ,Bass NM,Poordad FF,Sheikh MY,Frederick RT,Bortey E,Forbes WP.Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy.Clin Gastroenterol Hepatol 2014;12:1390-7.e2[PMID:24365449 DOI:10.1016/j.cgh.2013.12.021]
63 Mas A,Rodés J,Sunyer L,Rodrigo L,Planas R,Vargas V,Castells L,Rodríguez-Martínez D,FernándezRodríguez C,Coll I,Pardo A;Spanish Association for the Study of the Liver Hepatic Encephalopathy Cooperative Group.Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy:Results of a randomized,double-blind,double-dummy,controlled clinical trial.J Hepatol 2003;38:51-58[PMID:12480560 DOI:10.1016/S0168-8278(02)00350-1]
64 Bass NM,Mullen KD,Sanyal A,Poordad F,Neff G,Leevy CB,Sigal S,Sheikh MY,Beavers K,Frederick T,Teperman L,Hillebrand D,Huang S,Merchant K,Shaw A,Bortey E,Forbes WP.Rifaximin treatment in hepatic encephalopathy.N Engl J Med 2010;362:1071-1081[PMID:20335583 DOI:10.1056/NEJMoa0907893]
65 Kimer N,Gluud LL,Morris RW,Morgan MY.Rifaximin for the prevention and treatment of hepatic encephalopathy:A systematic review with meta-analyses of randomised controlled trials.J Clin Exp Hepatol 2017;7:S78-S79[DOI:10.1016/j.jceh.2017.01.105]
66 Wu D,Wu SM,Lu J,Zhou YQ,Xu L,Guo CY.Rifaximin versus Nonabsorbable Disaccharides for the Treatment of Hepatic Encephalopathy:A Meta-Analysis.Gastroenterol Res Pract 2013;2013:236963[PMID:23653636 DOI:10.1155/2013/236963]
67 Kang SH,Lee YB,Lee JH,Nam JY,Chang Y,Cho H,Yoo JJ,Cho YY,Cho EJ,Yu SJ,Kim MY,Kim YJ,Baik SK,Yoon JH.Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.Aliment Pharmacol Ther2017;46:845-855[PMID:28836723 DOI:10.1111/apt.14275]
68 Kabeshova A,Ben Hariz S,Tsakeu E,Benamouzig R,Launois R.Cost-effectiveness analysis of rifaximin-αadministration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France.Therap Adv Gastroenterol 2016;9:473-482[PMID:27366216 DOI:10.1177/1756283X16644249]
69 Vlachogiannakos J,Viazis N,Vasianopoulou P,Vafiadis I,Karamanolis DG,Ladas SD.Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis.JGastroenterol Hepatol 2013;28:450-455[PMID:23216382 DOI:10.1111/jgh.12070]
70 Hanouneh MA,Hanouneh IA,Hashash JG,Law R,Esfeh JM,Lopez R,Hazratjee N,Smith T,Zein NN.The role of rifaximin in the primary prophylaxis of spontaneous bacterial peritonitis in patients with liver cirrhosis.J Clin Gastroenterol 2012;46:709-715[PMID:22878533 DOI:10.1097/MCG.0b013e3182506dbb]
71 Runyon BA;AASLD Practice Guidelines Committee.Management of adult patients with ascites due to cirrhosis:An update.Hepatology 2009;49:2087-2107[PMID:19475696 DOI:10.1002/hep.22853]
72 European Association for the Study of the Liver.EASL clinical practice guidelines on the management of ascites,spontaneous bacterial peritonitis,and hepatorenal syndrome in cirrhosis.J Hepatol 2010;53:397-417[PMID:20633946 DOI:10.1016/j.jhep.2010.05.004]
73 Praharaj D,Taneja S,Duseja A,Chawla Y,Dhiman RK.Randomized Control Trial of Rifaximin and Norfloxacin in Primary and Secondary Prophylaxis of Spontaneous Bacterial Peritonitis(SBP)in Cirrhotic Patients.J Clin Exp Hepatol 2017;7:S71[DOI:10.1016/j.jceh.2017.05.133]
74 Sidhu GS,Go A,Attar BM,Mutneja HR,Arora S,Patel SA.Rifaximin versus norfloxacin for prevention of spontaneous bacterial peritonitis:A systematic review.BMJ Open Gastroenterol 2017;4:e000154[PMID:28944070 DOI:10.1136/bmjgast-2017-000154]
75 Kalambokis GN,Mouzaki A,Rodi M,Pappas K,Fotopoulos A,Xourgia X,Tsianos EV.Rifaximin improves systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites.Clin Gastroenterol Hepatol 2012;10:815-818[PMID:22391344 DOI:10.1016/j.cgh.2012.02.025]
76 Baik S,Lim Y,Cho Y,Kim M,Jang Y,Suk K,Cheon G,Kim Y,Choi D.G03:Rifaximin and propranolol combination therapy is more effective than propranolol monotherapy in the hepatic venous pressure gradient response and propranolol dose reduction-A pilot study.J Hepatol 2015;62:S188[DOI:10.1016/S0168-8278(15)30004-0]
77 Kimer N,Pedersen JS,Busk TM,Gluud LL,Hobolth L,Krag A,M?ller S,Bendtsen F;Copenhagen Rifaximin(Co Rif)Study Group.Rifaximin has no effect on hemodynamics in decompensated cirrhosis:Arandomized,double-blind,placebo-controlled trial.Hepatology 2017;65:592-603[PMID:27775818 DOI:10.1002/hep.28898]
78 Nathwani R.Rifaximin to reduce infection in decompensated cirrhosis.[accessed 2017 Sep 11].In:ISRCTN registry[Internet].Available from:https://doi.org/10.1186/ISRCTN10994757 ISRCTN number:ISRCTN10994757.
79 Goh ET,Stokes CS,Sidhu SS,Vilstrup H,Gluud LL,Morgan MY.L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis.Cochrane Database Syst Rev 2018;5:CD012410[PMID:29762873 DOI:10.1002/14651858.CD012410.pub2]
80 Bai M,Yang Z,Qi X,Fan D,Han G.l-ornithine-l-aspartate for hepatic encephalopathy in patients with cirrhosis:A meta-analysis of randomized controlled trials.J Gastroenterol Hepatol 2013;28:783-792[PMID:23425108 DOI:10.1111/jgh.12142]
81 Sidhu SS.L-ornithine L-aspartate in Overt Hepatic Encephalopathy(HEAL).[accessed 2017 Aug 2].In:Clinical Trials.gov[Internet].Bethesda(MD):U.S.National Library of Medicine.Available from:https://clinicaltrials.gov/ct2/show/NCT01722578 Clinical Trials.gov Identifier:NCT01722578.L-ornithine L-aspartate in Overt Hepatic Encephalopathy(HEAL).[accessed
82 Gentile S,Guarino G,Romano M,Alagia IA,Fierro M,Annunziata S,Magliano PL,Gravina AG,Torella R.A randomized controlled trial of acarbose in hepatic encephalopathy.Clin Gastroenterol Hepatol 2005;3:184-191[PMID:15704053 DOI:10.1016/S1542-3565(04)00667-6]
83 Mullen KD,Howard R.Is acarbose an effective drug for treating patients with cirrhosis and hepatic encephalopathy?Nat Clin Pract Gastroenterol Hepatol 2005;2:264-265[PMID:16265229 DOI:10.1038/ncpgasthep0194]
84 Ventura-Cots M,Santos B,GenescàJ.α1 andα2-adrenergic agonists on cirrhotic patients with refractory ascites.Liver Int 2016;36:177-180[PMID:26284943 DOI:10.1111/liv.12941]
85 Moore KP,Aithal GP.Guidelines on the management of ascites in cirrhosis.Gut 2006;55 Suppl 6:vi1-v12[PMID:16966752 DOI:10.1136/gut.2006.099580]
86 Piano S,Tonon M,Angeli P.Management of ascites and hepatorenal syndrome.Hepatol Int 2018;12:122-134[PMID:28836115 DOI:10.1007/s12072-017-9815-0]
87 Ginès P,Cárdenas A,Arroyo V,Rodés J.Management of cirrhosis and ascites.N Engl J Med 2004;350:1646-1654[PMID:15084697 DOI:10.1056/NEJMra035021]
88 Moore KP,Wong F,Gines P,Bernardi M,Ochs A,Salerno F,Angeli P,Porayko M,Moreau R,GarciaTsao G,Jimenez W,Planas R,Arroyo V.The management of ascites in cirrhosis:Report on the consensus conference of the International Ascites Club.Hepatology 2003;38:258-266[PMID:12830009 DOI:10.1053/jhep.2003.50315]
89 Sherlock S,Walker JG,Senewiratne B,Scott A.The complications of diuretic therapy in patients with cirrhosis.Ann N Y Acad Sci 1966;139:497-505[PMID:5230290 DOI:10.1111/j.1749-6632.1966.tb41223.x]
90 Laffi G,La Villa G,Carloni V,Foschi M,Bartoletti L,Quartini M,Gentilini P.Loop diuretic therapy in liver cirrhosis with ascites.J Cardiovasc Pharmacol 1993;22 Suppl 3:S51-S58[PMID:7506337 DOI:10.1097/00005344-199322003-00007]
91 Tsochatzis EA,Gerbes AL.Diagnosis and treatment of ascites.J Hepatol 2017;67:184-185[PMID:28119010 DOI:10.1016/j.jhep.2017.01.011]
92 Senousy BE,Draganov PV.Evaluation and management of patients with refractory ascites.World JGastroenterol 2009;15:67-80[PMID:19115470 DOI:10.3748/wjg.15.67]
93 Mukerji AN,Patel V,Jain A.Improving survival in decompensated cirrhosis.Int J Hepatol 2012;2012:318627[PMID:22811919 DOI:10.1155/2012/318627]
94 Singh V,Singh A,Singh B,Vijayvergiya R,Sharma N,Ghai A,Bhalla A.Midodrine and clonidine in patients with cirrhosis and refractory or recurrent ascites:A randomized pilot study.Am J Gastroenterol2013;108:560-567[PMID:23419385 DOI:10.1038/ajg.2013.9]
95 Singh V,Dhungana SP,Singh B,Vijayverghia R,Nain CK,Sharma N,Bhalla A,Gupta PK.Midodrine in patients with cirrhosis and refractory or recurrent ascites:A randomized pilot study.J Hepatol 2012;56:348-354[PMID:21749847 DOI:10.1016/j.jhep.2011.04.027]
96 Guo TT,Yang Y,Song Y,Ren Y,Liu ZX,Cheng G.Effects of midodrine in patients with ascites due to cirrhosis:Systematic review and meta-analysis.J Dig Dis 2016;17:11-19[PMID:26630543 DOI:10.1111/1751-2980.12304]
97 Patel S,Nguyen DS,Rastogi A,Nguyen MK,Nguyen MK.Treatment of Cirrhosis-Associated Hyponatremia with Midodrine and Octreotide.Front Med(Lausanne)2017;4:17[PMID:28352627 DOI:10.3389/fmed.2017.00017]
98 Lenaerts A,Codden T,Meunier JC,Henry JP,Ligny G.Effects of clonidine on diuretic response in ascitic patients with cirrhosis and activation of sympathetic nervous system.Hepatology 2006;44:844-849[PMID:17006921 DOI:10.1002/hep.21355]
99 SansoèG,Aragno M,Mastrocola R,Parola M.Dose-dependency of clonidine's effects in ascitic cirrhotic rats:Comparison withα1-adrenergic agonist midodrine.Liver Int 2016;36:205-211[PMID:26121993DOI:10.1111/liv.12905]
100 Yan L,Xie F,Lu J,Ni Q,Shi C,Tang C,Yang J.The treatment of vasopressin V2-receptor antagonists in cirrhosis patients with ascites:A meta-analysis of randomized controlled trials.BMC Gastroenterol 2015;15:65[PMID:26054761 DOI:10.1186/s12876-015-0297-z]
101 Pose E,Cardenas A.Translating Our Current Understanding of Ascites Management into New Therapies for Patients with Cirrhosis and Fluid Retention.Dig Dis 2017;35:402-410[PMID:28468013 DOI:10.1159/000456595]
102 Wong F,Watson H,Gerbes A,Vilstrup H,Badalamenti S,Bernardi M,Ginès P;Satavaptan Investigators Group.Satavaptan for the management of ascites in cirrhosis:Efficacy and safety across the spectrum of ascites severity.Gut 2012;61:108-116[PMID:21836029 DOI:10.1136/gutjnl-2011-300157]
103 Vargas JI,Arrese M,Shah VH,Arab JP.Use of Statins in Patients with Chronic Liver Disease and Cirrhosis:Current Views and Prospects.Curr Gastroenterol Rep 2017;19:43[PMID:28752475 DOI:10.1007/s11894-017-0584-7]
104 Cabrera L,Abraldes JG.Statins:The Panacea of Cirrhosis?Curr Hepatol Rep 2016;15:1-7[DOI:10.1007/s11901-016-0287-9]
105 Zafra C,Abraldes JG,Turnes J,Berzigotti A,Fernández M,Garca-Pagán JC,Rodés J,Bosch J.Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis.Gastroenterology 2004;126:749-755[PMID:14988829 DOI:10.1053/j.gastro.2003.12.007]
106 Abraldes JG,Albillos A,Ba?ares R,Turnes J,González R,García-Pagán JC,Bosch J.Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension:A randomized controlled trial.Gastroenterology 2009;136:1651-1658[PMID:19208350 DOI:10.1053/j.gastro.2009.01.043]
107 Kumar S,Grace ND,Qamar AA.Statin use in patients with cirrhosis:A retrospective cohort study.Dig Dis Sci 2014;59:1958-1965[PMID:24838495 DOI:10.1007/s10620-014-3179-2]
108 Mohanty A,Tate JP,Garcia-Tsao G.Statins Are Associated With a Decreased Risk of Decompensation and Death in Veterans With Hepatitis C-Related Compensated Cirrhosis.Gastroenterology 2016;150:430-40.e1[PMID:26484707 DOI:10.1053/j.gastro.2015.10.007]
109 Chang FM,Wang YP,Lang HC,Tsai CF,Hou MC,Lee FY,Lu CL.Statins decrease the risk of decompensation in hepatitis B virus-and hepatitis C virus-related cirrhosis:A population-based study.Hepatology 2017;66:896-907[PMID:28318053 DOI:10.1002/hep.29172]
110 Abraldes JG,Villanueva C,Aracil C,Turnes J,Hernandez-Guerra M,Genesca J,Rodriguez M,Castellote J,García-Pagán JC,Torres F,Calleja JL,Albillos A,Bosch J;BLEPS Study Group.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;150:1160-1170.e3[PMID:26774179 DOI:10.1053/j.gastro.2016.01.004]
111 Kamal S,Khan MA,Seth A,Cholankeril G,Gupta D,Singh U,Kamal F,Howden CW,Stave C,Nair S,Satapathy SK,Ahmed A.Beneficial Effects of Statins on the Rates of Hepatic Fibrosis,Hepatic Decompensation,and Mortality in Chronic Liver Disease:A Systematic Review and Meta-Analysis.Am JGastroenterol 2017;112:1495-1505[PMID:28585556 DOI:10.1038/ajg.2017.170]
112 Kim RG,Loomba R,Prokop LJ,Singh S.Statin Use and Risk of Cirrhosis and Related Complications in Patients With Chronic Liver Diseases:A Systematic Review and Meta-analysis.Clin Gastroenterol Hepatol 2017;15:1521-1530.e8[PMID:28479502 DOI:10.1016/j.cgh.2017.04.039]
113 Singh S,Singh PP,Singh AG,Murad MH,Sanchez W.Statins are associated with a reduced risk of hepatocellular cancer:A systematic review and meta-analysis.Gastroenterology 2013;144:323-332[PMID:23063971 DOI:10.1053/j.gastro.2012.10.005]
114 Tsochatzis EA,Bosch J.Statins in cirrhosis-Ready for prime time.Hepatology 2017;66:697-699[PMID:28543643 DOI:10.1002/hep.29277]
115 Chalasani N,Aljadhey H,Kesterson J,Murray MD,Hall SD.Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity.Gastroenterology 2004;126:1287-1292[PMID:15131789 DOI:10.1053/j.gastro.2004.02.015]
116 Lewis JH,Mortensen ME,Zweig S,Fusco MJ,Medoff JR,Belder R;Pravastatin in Chronic Liver Disease Study Investigators.Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease:Results of a prospective,randomized,double-blind,placebocontrolled,multicenter trial.Hepatology 2007;46:1453-1463[PMID:17668878 DOI:10.1002/hep.21848]
117 Chalasani N,Younossi Z,Lavine JE,Charlton M,Cusi K,Rinella M,Harrison SA,Brunt EM,Sanyal AJ.The diagnosis and management of nonalcoholic fatty liver disease:Practice guidance from the American Association for the Study of Liver Diseases.Hepatology 2018;67:328-357[PMID:28714183 DOI:10.1002/hep.29367]
118 European Association for the Study of the Liver(EASL).;European Association for the Study of Diabetes(EASD);European Association for the Study of Obesity(EASO).EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease.Obes Facts 2016;9:65-90[PMID:27055256 DOI:10.1159/000443344]
119 Moctezuma-Velázquez C,Abraldes JG,Montano-Loza AJ.The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis.Curr Treat Options Gastroenterol 2018;16:226-240[PMID:29572618 DOI:10.1007/s11938-018-0180-4]
120 Lodato F,Azzaroli F,Di Girolamo M,Feletti V,Cecinato P,Lisotti A,Festi D,Roda E,Mazzella G.Proton pump inhibitors in cirrhosis:Tradition or evidence based practice?World J Gastroenterol 2008;14:2980-2985[PMID:18494046 DOI:10.3748/wjg.14.2980]
121 Dam G,Vilstrup H,Watson H,Jepsen P.Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites.Hepatology2016;64:1265-1272[PMID:27474889 DOI:10.1002/hep.28737]
122 Dultz G,Piiper A,Zeuzem S,Kronenberger B,Waidmann O.Proton pump inhibitor treatment is associated with the severity of liver disease and increased mortality in patients with cirrhosis.Aliment Pharmacol Ther 2015;41:459-466[PMID:25523381 DOI:10.1111/apt.13061]
123 Trikudanathan G,Israel J,Cappa J,O'Sullivan DM.Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients-a systematic review and meta-analysis.Int J Clin Pract 2011;65:674-678[PMID:21564440 DOI:10.1111/j.1742-1241.2011.02650.x]
124 Khan MA,Cholankeril G,Howden CW.Are proton pump inhibitors a threat for spontaneous bacterial peritonitis and hepatic encephalopathy in cirrhosis?Not so fast.Hepatology 2017;65:393[PMID:27688049 DOI:10.1002/hep.28858]
125 Tsai CF,Chen MH,Wang YP,Chu CJ,Huang YH,Lin HC,Hou MC,Lee FY,Su TP,Lu CL.Proton Pump Inhibitors Increase Risk for Hepatic Encephalopathy in Patients With Cirrhosis in A Population Study.Gastroenterology 2017;152:134-141[PMID:27639806 DOI:10.1053/j.gastro.2016.09.007]
126 Woodhouse CA,Patel VC,Singanayagam A,Shawcross DL.Review article:the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.Aliment Pharmacol Ther2018;47:192-202[PMID:29083037 DOI:10.1111/apt.14397]
127 Bajaj JS,Acharya C,Fagan A,White MB,Gavis E,Heuman DM,Hylemon PB,Fuchs M,Puri P,Schubert ML,Sanyal AJ,Sterling RK,Stravitz RT,Siddiqui MS,Luketic V,Lee H,Sikaroodi M,Gillevet PM.Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis.Am J Gastroenterol 2018;113:1177-1186[PMID:29872220 DOI:10.1038/s41395-018-0085-9]
128 Ratuapli SK,Ellington TG,O'Neill MT,Umar SB,Harris LA,Foxx-Orenstein AE,Burdick GE,Dibaise JK,Lacy BE,Crowell MD.Proton pump inhibitor therapy use does not predispose to small intestinal bacterial overgrowth.Am J Gastroenterol 2012;107:730-735[PMID:22334250 DOI:10.1038/ajg.2012.4]
129 Assaraf J,Weiss N,Thabut D.Proton Pump Inhibitor Administration Triggers Encephalopathy in Cirrhotic Patients by Modulating Blood-Brain Barrier Drug Transport.Gastroenterology 2017;152:2077[PMID:28478148 DOI:10.1053/j.gastro.2016.10.049]
130 Khan MA,Cholankeril G,Howden CW.Proton Pump Inhibitors and the Possible Development of Hepatic Encephalopathy in Cirrhotic Patients:True Association or Residual Confounding?Gastroenterology 2017;152:2076[PMID:28478154 DOI:10.1053/j.gastro.2016.10.050]
131 Terg R,Casciato P,Garbe C,Cartier M,Stieben T,Mendizabal M,Niveyro C,Benavides J,Marino M,Colombato L,Berbara D,Silva M,Salgado P,Barreyro F,Fassio E,Gadano A;Study Group of Cirrhosis Complications of the Argentine Association for the Study of Liver Disease.Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis:A multicenter prospective study.J Hepatol 2015;62:1056-1060[PMID:25481567 DOI:10.1016/j.jhep.2014.11.036]
132 Yu T,Tang Y,Jiang L,Zheng Y,Xiong W,Lin L.Proton pump inhibitor therapy and its association with spontaneous bacterial peritonitis incidence and mortality:A meta-analysis.Dig Liver Dis 2016;48:353-359[PMID:26795544 DOI:10.1016/j.dld.2015.12.009]
133 Dhar A,Mullish BH,Thursz MR.Anticoagulation in chronic liver disease.J Hepatol 2017;66:1313-1326[PMID:28088580 DOI:10.1016/j.jhep.2017.01.006]
134 Leonardi F,Maria N,Villa E.Anticoagulation in cirrhosis:A new paradigm?Clin Mol Hepatol 2017;23:13-21[PMID:28288507 DOI:10.3350/cmh.2016.0110]
135 Bitto N,Liguori E,La Mura V.Coagulation,Microenvironment and Liver Fibrosis.Cells 2018;7:pii:E85[PMID:30042349 DOI:10.3390/cells7080085]
136 Dabbagh O,Oza A,Prakash S,Sunna R,Saettele TM.Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease.Chest 2010;137:1145-1149[PMID:20040609 DOI:10.1378/chest.09-2177]
137 Villa E,CammàC,Marietta M,Luongo M,Critelli R,Colopi S,Tata C,Zecchini R,Gitto S,Petta S,Lei B,Bernabucci V,Vukotic R,De Maria N,Schepis F,Karampatou A,Caporali C,Simoni L,Del Buono M,Zambotto B,Turola E,Fornaciari G,Schianchi S,Ferrari A,Valla D.Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis.Gastroenterology 2012;143:1253-1260.e4[PMID:22819864 DOI:10.1053/j.gastro.2012.07.018]
138 Senzolo M,M Sartori T,Rossetto V,Burra P,Cillo U,Boccagni P,Gasparini D,Miotto D,Simioni P,Tsochatzis E,A Burroughs K.Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis.Liver Int 2012;32:919-927[PMID:22435854 DOI:10.1111/j.1478-3231.2012.02785.x]
139 Chen H,Liu L,Qi X,He C,Wu F,Fan D,Han G.Efficacy and safety of anticoagulation in more advanced portal vein thrombosis in patients with liver cirrhosis.Eur J Gastroenterol Hepatol 2016;28:82-89[PMID:26513611 DOI:10.1097/MEG.0000000000000482]
140 Delgado MG,Seijo S,Yepes I,Achécar L,Catalina MV,García-Criado A,Abraldes JG,de la Pe?a J,Ba?ares R,Albillos A,Bosch J,García-Pagán JC.Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis.Clin Gastroenterol Hepatol 2012;10:776-783[PMID:22289875DOI:10.1016/j.cgh.2012.01.012]
141 Amitrano L,Guardascione MA,Menchise A,Martino R,Scaglione M,Giovine S,Romano L,Balzano A.Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis.J Clin Gastroenterol 2010;44:448-451[PMID:19730112DOI:10.1097/MCG.0b013e3181b3ab44]
142 Bernardi M,Maggioli C,Zaccherini G.Human albumin in the management of complications of liver cirrhosis.Crit Care 2012;16:211[PMID:22429536]
143 Arroyo V,García-Martinez R,Salvatella X.Human serum albumin,systemic inflammation,and cirrhosis.J Hepatol 2014;61:396-407[PMID:24751830 DOI:10.1016/j.jhep.2014.04.012]
144 Garcia-Martinez R,Caraceni P,Bernardi M,Gines P,Arroyo V,Jalan R.Albumin:Pathophysiologic basis of its role in the treatment of cirrhosis and its complications.Hepatology 2013;58:1836-1846[PMID:23423799 DOI:10.1002/hep.26338]
145 Salerno F,Navickis RJ,Wilkes MM.Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis:A meta-analysis of randomized trials.Clin Gastroenterol Hepatol 2013;11:123-30.e1[PMID:23178229 DOI:10.1016/j.cgh.2012.11.007]
146 Sanyal AJ,Boyer T,Garcia-Tsao G,Regenstein F,Rossaro L,Appenrodt B,Blei A,Gülberg V,Sigal S,Teuber P;Terlipressin Study Group.A randomized,prospective,double-blind,placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome.Gastroenterology 2008;134:1360-1368[PMID:18471513DOI:10.1053/j.gastro.2008.02.014]
147 Bernardi M,Caraceni P,Navickis RJ,Wilkes MM.Albumin infusion in patients undergoing largevolume paracentesis:A meta-analysis of randomized trials.Hepatology 2012;55:1172-1181[PMID:22095893 DOI:10.1002/hep.24786]
148 Caraceni P,Riggio O,Angeli P,Alessandria C,Neri S,Foschi FG,Levantesi F,Airoldi A,Boccia S,Svegliati-Baroni G,Fagiuoli S,Romanelli RG,Cozzolongo R,Di Marco V,Sangiovanni V,Morisco F,Toniutto P,Tortora A,De Marco R,Angelico M,Cacciola I,Elia G,Federico A,Massironi S,Guarisco R,Galioto A,Ballardini G,Rendina M,Nardelli S,Piano S,Elia C,Prestianni L,Cappa FM,Cesarini L,Simone L,Pasquale C,Cavallin M,Andrealli A,Fidone F,Ruggeri M,Roncadori A,Baldassarre M,Tufoni M,Zaccherini G,Bernardi M;ANSWER Study Investigators.Long-term albumin administration in decompensated cirrhosis(ANSWER):An open-label randomised trial.Lancet 2018;391:2417-2429[PMID:29861076 DOI:10.1016/S0140-6736(18)30840-7]
149 Mullish BH,Quraishi MN,Segal JP,Mc Cune VL,Baxter M,Marsden GL,Moore DJ,Colville A,Bhala N,Iqbal TH,Settle C,Kontkowski G,Hart AL,Hawkey PM,Goldenberg SD,Williams HRT.The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications:Joint British Society of Gastroenterology(BSG)and Healthcare Infection Society(HIS)guidelines.Gut 2018;67:1920-1941[PMID:30154172 DOI:10.1136/gutjnl-2018-316818]
150 Bajaj JS,Kassam Z,Fagan A,Gavis EA,Liu E,Cox IJ,Kheradman R,Heuman D,Wang J,Gurry T,Williams R,Sikaroodi M,Fuchs M,Alm E,John B,Thacker LR,Riva A,Smith M,Taylor-Robinson SD,Gillevet PM.Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy:Arandomized clinical trial.Hepatology 2017;66:1727-1738[PMID:28586116 DOI:10.1002/hep.29306]
151 Woodhouse C.Trial of faecal microbiota transplantation in cirrhosis.ISRCTN registry.[accessed 2018May 21].In:ISRCTN registry[Internet].Available from:https://doi.org/10.1186/ISRCTN11814003ISRCTN number:ISRCTN11814003.
152 Dranoff JA.Coffee Consumption and Prevention of Cirrhosis:In Support of the Caffeine Hypothesis.Gene Expr 2018;18:1-3[PMID:28893365 DOI:10.3727/105221617X15046391179559]
153 Salomone F,Galvano F,Li Volti G.Molecular Bases Underlying the Hepatoprotective Effects of Coffee.Nutrients 2017;9:pii:E85[PMID:28124992 DOI:10.3390/nu9010085]
154 Petta S,Marchesini G.Coffee and tea breaks for liver health.J Hepatol 2017;67:221-223[PMID:28578838 DOI:10.1016/j.jhep.2017.04.014]
155 Corrao G,Zambon A,Bagnardi V,D'Amicis A,Klatsky A;Collaborative SIDECIR Group.Coffee,caffeine,and the risk of liver cirrhosis.Ann Epidemiol 2001;11:458-465[PMID:11557177 DOI:10.1016/S1047-2797(01)00223-X]
156 Alferink LJM,Fittipaldi J,Kiefte-de Jong JC,Taimr P,Hansen BE,Metselaar HJ,Schoufour JD,Ikram MA,Janssen HLA,Franco OH,Darwish Murad S.Coffee and herbal tea consumption is associated with lower liver stiffness in the general population:The Rotterdam study.J Hepatol 2017;67:339-348[PMID:28578837 DOI:10.1016/j.jhep.2017.03.013]
157 Yu C,Cao Q,Chen P,Yang S,Deng M,Wang Y,Li L.An updated dose-response meta-analysis of coffee consumption and liver cancer risk.Sci Rep 2016;6:37488[PMID:27910873 DOI:10.1038/srep37488]
158 Freedman ND,Everhart JE,Lindsay KL,Ghany MG,Curto TM,Shiffman ML,Lee WM,Lok AS,Di Bisceglie AM,Bonkovsky HL,Hoefs JC,Dienstag JL,Morishima C,Abnet CC,Sinha R;HALT-C Trial Group.Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C.Hepatology 2009;50:1360-1369[PMID:19676128 DOI:10.1002/hep.23162]