Medical Management of Portal Hypertension and Its Complications

Abstract

Portal hypertension, most commonly caused by cirrhosis, is defined as an elevated hepatic venous pressure gradient that can lead to complications including ascites, hepatic, esophageal/gastric varices, hepatic encephalopathy, and hepatorenal syndrome. While these complications are initially managed by medical and endoscopic treatments, progressive decompensation of liver disease may lead to liver transplantation.

Keywords

portal hypertension - cirrhosis - medical management

• References

• 1 Volk ML, Tocco RS, Bazick J, Rakoski MO, Lok AS. Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol 2012; 107 (02) 247-252
• 2 Kochanek KD, Xu J, Murphy SL, Miniño AM, Kung H-C. Deaths: final data for 2009. Natl Vital Stat Rep 2011; 60 (03) 1-116
• 3 Armonis A, Patch D, Burroughs A. Hepatic venous pressure measurement: an old test as a new prognostic marker in cirrhosis?. Hepatology 1997; 25 (01) 245-248
• 4 Sanyal AJ, Bosch J, Blei A, Arroyo V. Portal hypertension and its complications. Gastroenterology 2008; 134 (06) 1715-1728
• 5 Vorobioff J, Bredfeldt JE, Groszmann RJ. Increased blood flow through the portal system in cirrhotic rats. Gastroenterology 1984; 87 (05) 1120-1126
• 6 Pizcueta MP, Piqué JM, Bosch J, Whittle BJ, Moncada S. Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension. Br J Pharmacol 1992; 105 (01) 184-190
• 7 Bosch J, Abraldes JG, Groszmann R. Current management of portal hypertension. J Hepatol 2003; 38 (Suppl. 01) S54-S68
• 8 Bataller R, Ginès P, Nicolás JM. , et al. Angiotensin II induces contraction and proliferation of human hepatic stellate cells. Gastroenterology 2000; 118 (06) 1149-1156
• 9 Gupta TK, Toruner M, Chung MK, Groszmann RJ. Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats. Hepatology 1998; 28 (04) 926-931
• 10 Gupta TK, Toruner M, Groszmann RJ. Intrahepatic modulation of portal pressure and its role in portal hypertension. Role of nitric oxide. Digestion 1998; 59 (04) 413-415
• 11 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. Hepatotlogy 2017; 65 (01) 310-335
• 12 Ripoll C, Groszmann R, Garcia-Tsao G. , et al; Portal Hypertension Collaborative Group. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology 2007; 133 (02) 481-488
• 13 Casado M, Bosch J, García-Pagán JC. , et al. Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings. Gastroenterology 1998; 114 (06) 1296-1303
• 14 Garcia-Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickman M. Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology 1985; 5 (03) 419-424
• 15 Ripoll C, Bañares R, Rincón D. , et al. Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era. Hepatology 2005; 42 (04) 793-801
• 16 Ginés P, Quintero E, Arroyo V. , et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology 1987; 7 (01) 122-128
• 17 Fernández-Esparrach G, Sánchez-Fueyo A, Ginès P. , et al. A prognostic model for predicting survival in cirrhosis with ascites. J Hepatol 2001; 34 (01) 46-52
• 18 Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodés J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology 1988; 8 (05) 1151-1157
• 19 Arroyo V, Bosch J, Mauri M, Ribera F, Navarro-López F, Rodés J. Effect of angiotensin-II blockade on systemic and hepatic haemodynamics and on the renin-angiotensin-aldosterone system in cirrhosis with ascites. Eur J Clin Invest 1981; 11 (03) 221-229
• 20 Bosch J, Arroyo V, Betriu A. , et al. Hepatic hemodynamics and the renin-angiotensin-aldosterone system in cirrhosis. Gastroenterology 1980; 78 (01) 92-99
• 21 Witte MH, Witte CL, Dumont AE. Progress in liver disease: physiological factors involved in the causation of cirrhotic ascites. Gastroenterology 1971; 61 (05) 742-750
• 22 Runyon BA. . AASLD PRACTICE GUIDELINE. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis. Hepatology. 2013; 57 (04) 1651-1653
• 23 Pérez-Ayuso RM, Arroyo V, Planas R. , et al. Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites. Relationship between the diuretic response and the activity of the renin-aldosterone system. Gastroenterology 1983; 84 (5 Pt 1): 961-968
• 24 Santos J, Planas R, Pardo A. , et al. Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety. J Hepatol 2003; 39 (02) 187-192
• 25 Angeli P, Fasolato S, Mazza E. , et al. Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial. Gut 2010; 59 (01) 98-104
• 26 Angeli P, Dalla Pria M, De Bei E. , et al. Randomized clinical study of the efficacy of amiloride and potassium canrenoate in nonazotemic cirrhotic patients with ascites. Hepatology 1994; 19 (01) 72-79
• 27 Ginés P, Arroyo V, Quintero E. , et al. Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study. Gastroenterology 1987; 93 (02) 234-241
• 28 Bernardi M, Caraceni P, Navickis RJ, Wilkes MM. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology 2012; 55 (04) 1172-1181
• 29 Sersté T, Melot C, Francoz C. , et al. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology 2010; 52 (03) 1017-1022
• 30 Bang UC, Benfield T, Hyldstrup L, Jensen J-EB, Bendtsen F. Effect of propranolol on survival in patients with decompensated cirrhosis: a nationwide study based Danish patient registers. Liver Int 2016; 36 (09) 1304-1312
• 31 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 (01) 40-46
• 32 Garbuzenko DV, Arefyev NO. Hepatic hydrothorax: an update and review of the literature. World J Hepatol 2017; 9 (31) 1197-1204
• 33 Abbasi A, Bhutto AR, Alam MT, Aurangzaib M, Masroor M. Frequency of hepatic hydrothorax and its association with Child–Pugh class in liver cirrhosis patients. J Coll Physicians Surg Pak 2016; 26 (07) 566-569
• 34 Sharaf-Eldin M, Bediwy AS, Kobtan A. , et al. Pigtail catheter: a less invasive option for pleural drainage in egyptian patients with recurrent hepatic hydrothorax. Gastroenterol Res Pract 2016; 2016: 4013052
• 35 Coelho-Prabhu N, Kamath PS. Current staging and diagnosis of gastroesophageal varices. Clin Liver Dis 2010; 14 (02) 195-208
• 36 Moitinho E, Escorsell A, Bandi JC. , et al. Prognostic value of early measurements of portal pressure in acute variceal bleeding. Gastroenterology 1999; 117 (03) 626-631
• 37 de Franchis R. ; Baveno VI Faculty. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63 (03) 743-752
• 38 Groszmann RJ, Garcia-Tsao G, Bosch J. , et al; Portal Hypertension Collaborative Group. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005; 353 (21) 2254-2261
• 39 D'Amico G, Garcia-Pagan JC, Luca A, Bosch J. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: a systematic review. Gastroenterology 2006; 131 (05) 1611-1624
• 40 Calés P, Oberti F, Payen JL. , et al; French-Speaking Club for the Study of Portal Hypertension. Lack of effect of propranolol in the prevention of large oesophageal varices in patients with cirrhosis: a randomized trial. Eur J Gastroenterol Hepatol 1999; 11 (07) 741-745
• 41 Bhardwaj A, Kedarisetty CK, Vashishtha C. , et al. Carvedilol delays the progression of small oesophageal varices in patients with cirrhosis: a randomised placebo-controlled trial. Gut 2017; 66 (10) 1838-1843
• 42 Merkel C, Marin R, Angeli P. , et al; Gruppo Triveneto per l'Ipertensione Portale. A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis. Gastroenterology 2004; 127 (02) 476-484
• 43 Sarin SK, Lamba GS, Kumar M, Misra A, Murthy NS. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. N Engl J Med 1999; 340 (13) 988-993
• 44 Gluud LL, Krag A. Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults. Cochrane Database Syst Rev 2012; (08) CD004544
• 45 Khuroo MS, Khuroo NS, Farahat KLC, Khuroo YS, Sofi AA, Dahab ST. Meta-analysis: endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleeding. Aliment Pharmacol Ther 2005; 21 (04) 347-361
• 46 Shah HA, Azam Z, Rauf J. , et al. Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: a multicentre randomized controlled trial. J Hepatol 2014; 60 (04) 757-764
• 47 Sarin SK, Wadhawan M, Agarwal SR, Tyagi P, Sharma BC. Endoscopic variceal ligation plus propranolol versus endoscopic variceal ligation alone in primary prophylaxis of variceal bleeding. Am J Gastroenterol 2005; 100 (04) 797-804
• 48 Villanueva C, Colomo A, Bosch A. , et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368 (01) 11-21
• 49 Wells M, Chande N, Adams P. , et al. Meta-analysis: vasoactive medications for the management of acute variceal bleeds. Aliment Pharmacol Ther 2012; 35 (11) 1267-1278
• 50 Hwang JH, Shergill AK, Acosta RD. , et al; American Society for Gastrointestinal Endoscopy. The role of endoscopy in the management of variceal hemorrhage. Gastrointest Endosc 2014; 80 (02) 221-227
• 51 García-Pagán JC, Caca K, Bureau C. , et al; Early TIPS (Transjugular Intrahepatic Portosystemic Shunt) Cooperative Study Group. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 2010; 362 (25) 2370-2379
• 52 Albillos A, Zamora J, Martínez J. , et al; Baveno Cooperation. Stratifying risk in the prevention of recurrent variceal hemorrhage: results of an individual patient meta-analysis. Hepatology 2017; 66 (04) 1219-1231
• 53 Trebicka J, Hennenberg M, Laleman W. , et al. Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology 2007; 46 (01) 242-253
• 54 Zafra C, Abraldes JG, Turnes J. , et al. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology 2004; 126 (03) 749-755
• 55 Abraldes JG, Villanueva C, Aracil C. , et al; 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 (05) 1160-1170.e3
• 56 Lo EAG, Wilby KJ, Ensom MHH. Use of proton pump inhibitors in the management of gastroesophageal varices: a systematic review. Ann Pharmacother 2015; 49 (02) 207-219
• 57 Sarin SK, Lahoti D, Saxena SP, Murthy NS, Makwana UK. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology 1992; 16 (06) 1343-1349
• 58 Ríos Castellanos E, Seron P, Gisbert JP, Bonfill Cosp X. Endoscopic injection of cyanoacrylate glue versus other endoscopic procedures for acute bleeding gastric varices in people with portal hypertension. Cochrane Database Syst Rev 2015; (05) CD010180
• 59 Gentilini P, Laffi G, La Villa G. , et al. Long course and prognostic factors of virus-induced cirrhosis of the liver. Am J Gastroenterol 1997; 92 (01) 66-72
• 60 Bajaj JS. Review article: potential mechanisms of action of rifaximin in the management of hepatic encephalopathy and other complications of cirrhosis. Aliment Pharmacol Ther 2016; 43 (Suppl. 01) 11-26
• 61 Parekh PJ, Balart LA. Ammonia and its role in the pathogenesis of hepatic encephalopathy. Clin Liver Dis 2015; 19 (03) 529-537
• 62 Aldridge DR, Tranah EJ, Shawcross DL. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. J Clin Exp Hepatol 2015; 5 (Suppl. 01) S7-S20
• 63 Watanabe M, Ozaki T, Hirata Y. , et al. Mechanism for lowering blood ammonia levels by lactitol. Jpn J Pharmacol 1995; 67 (04) 369-374
• 64 Schiano TD. Treatment options for hepatic encephalopathy. Pharmacotherapy 2010; 30 (5 Pt 2): 16S-21S
• 65 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; CD003044
• 66 Di Piazza S, Gabriella Filippazzo M, Valenza LM. , et al. Rifaximine versus neomycin in the treatment of portosystemic encephalopathy. Ital J Gastroenterol 1991; 23 (07) 403-407
• 67 Mullen KD, Sanyal AJ, Bass NM. , et al. Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy. Clin Gastroenterol Hepatol 2014; 12 (08) 1390-7.e2
• 68 Pedretti G, Calzetti C, Missale G, Fiaccadori F. Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial. Ital J Gastroenterol 1991; 23 (04) 175-178
• 69 Bass NM, Mullen KD, Sanyal A. , et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 2010; 362 (12) 1071-1081
• 70 Sharma BC, Sharma P, Lunia MK, Srivastava S, Goyal R, Sarin SKA. A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol 2013; 108 (09) 1458-1463
• 71 Kabeshova A, Ben Hariz S, Tsakeu E, Benamouzig R, Launois R. Cost-effectiveness analysis of rifaximin-α administration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France. Therap Adv Gastroenterol 2016; 9 (04) 473-482
• 72 Poo JL, Rosas-Romero R, Rodríguez F. , et al. Serum zinc concentrations in two cohorts of 153 healthy subjects and 100 cirrhotic patients from Mexico City. Dig Dis 1995; 13 (02) 136-142
• 73 Rahelić D, Kujundzić M, Romić Z, Brkić K, Petrovecki M. Serum concentration of zinc, copper, manganese and magnesium in patients with liver cirrhosis. Coll Antropol 2006; 30 (03) 523-528
• 74 Jawaro T, Yang A, Dixit D, Bridgeman MB. Management of Hepatic Encephalopathy: A Primer. Ann Pharmacother 2016; 50 (07) 569-577
• 75 Chavez-Tapia NC, Cesar-Arce A, Barrientos-Gutiérrez T, Villegas-López FA, Méndez-Sanchez N, Uribe M. A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy. Nutr J 2013; 12: 74
• 76 Dalal R, McGee RG, Riordan SM, Webster AC. Probiotics for people with hepatic encephalopathy. Cochrane Database Syst Rev 2017; CD008716
• 77 Saab S, Suraweera D, Au J, Saab EG, Alper TS, Tong MJ. Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials. Liver Int 2016; 36 (07) 986-993
• 78 Bian J, Wang A, Lin J. , et al. Association between proton pump inhibitors and hepatic encephalopathy: a meta-analysis. Medicine (Baltimore) 2017; 96 (17) e6723
• 79 Tsai C-F, Chen M-H, Wang Y-P. , et al. Proton. Gastroenterology 2017; 152 (01) 134-141
• 80 Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Postgrad Med J 2008; 84 (998) 662-670
• 81 Israelsen M, Krag A, Allegretti AS. , et al. Terlipressin versus other vasoactive drugs for hepatorenal syndrome. Cochrane Database Syst Rev 2017; 9: CD011532
• 82 Nanda A, Reddy R, Safraz H, Habeeb S, Singal AK. Pharmacological therapies for hepatorenal syndrome: a systematic review and meta-analysis. J Clin Gastroenterol 2017; ;(Oct): 1