This article is part of the Topical Collection on Management of Cirrhotic Patient
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While portal hypertension (PHT) treatment strategies for patients with advanced chronic liver disease (ACLD) are well established, studies on the management of PHT after orthotopic liver transplantation (OLT) are limited. This is due to the heterogeneous causes of portal hypertension in the OLT setting.
Specific recommendations for the management of non-alcoholic steatohepatitis (NASH), including medical and surgical therapeutic options, and hepatitis C virus (HCV) infection after OLT, are available with most of them applying to transplanted patients. Important concepts to prevent and manage portal vein thrombosis (PVT)—including anticoagulation and TIPS implantation—have been developed. Surgical approaches to resolve PVT, when encountered intraoperatively, have been refined. Finally, interventional treatment options for PHT-related complications and hepatic venous outflow obstruction are available.
NASH has a high recurrence rate and causes considerable postoperative morbidity. HCV can be successfully treated in most cases. Specific medical and interventional as well as surgical treatment options are available for PHT after OLT—including for PHT due to surgical complications.
de Franchis R, Baveno VIF. Expanding consensus in portal hypertension: report of the Baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743–52. CrossRef
Graziadei I, Zoller H, Fickert P, Schneeberger S, Finkenstedt A, Peck-Radosavljevic M, et al. Indications for liver transplantation in adults : recommendations of the Austrian Society for Gastroenterology and Hepatology (OGGH) in cooperation with the Austrian Society for Transplantation, Transfusion and Genetics (ATX). Wien Klin Wochenschr. 2016;128(19–20):679–90. CrossRef
Unger LW, Berlakovich GA, Trauner M, Reiberger T. Management of portal hypertension before and after liver transplantation. Liver Transpl. 2018;24(1):112–21. CrossRef
Reiberger T, Puspok A, Schoder M, Baumann-Durchschein F, Bucsics T, Datz C, et al. Austrian consensus guidelines on the management and treatment of portal hypertension (Billroth III). Wien Klin Wochenschr. 2017;129(Suppl 3):135–58. CrossRef
Mandorfer M, Schwabl P, Steiner S, Reiberger T, Peck-Radosavljevic M. Advances in the management of HIV/HCV coinfection. Hepatol Int. 2016;10(3):424–35. CrossRef
Ferenci P, Kozbial K, Mandorfer M, Hofer H. HCV targeting of patients with cirrhosis. J Hepatol. 2015;63(4):1015–22. CrossRef
Mandorfer M, Kozbial K, Schwabl P, Freissmuth C, Schwarzer R, Stern R, et al. Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension. J Hepatol. 2016;65(4):692–9. CrossRef
Schwabl P, Mandorfer M, Steiner S, Scheiner B, Chromy D, Herac M, et al. Interferon-free regimens improve portal hypertension and histological necroinflammation in HIV/HCV patients with advanced liver disease. Aliment Pharmacol Ther. 2017;45(1):139–49. CrossRef
Lens S, Alvarado-Tapias E, Marino Z, Londono MC, LL E, Martinez J, et al. Effects of all-oral anti-viral therapy on HVPG and systemic hemodynamics in patients with hepatitis C virus-associated cirrhosis. Gastroenterology. 2017;153(5):1273–83 e1271. CrossRef
Afdhal N, Everson GT, Calleja JL, McCaughan GW, Bosch J, Brainard DM, et al. Effect of viral suppression on hepatic venous pressure gradient in hepatitis C with cirrhosis and portal hypertension. J Viral Hepat. 2017;24(10):823–31. CrossRef
•• Ripoll C, Groszmann R, Garcia-Tsao G, Grace N, Burroughs A, Planas R, et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133(2):481–8. This study identified a HVPG of 10 mmHg as an independent predictor for subsequent hepatic decompensation. CrossRef
Scheiner B, Steininger L, Semmler G, Unger LW, Schwabl P, Bucsics T, et al. Controlled attenuation parameter (CAP) does not predict hepatic decompensation in patients with advanced chronic liver disease. Liver Int. 2019;39(1):127–35. https://doi.org/10.1111/liv.13943.
Crespo G, Trota N, Londono MC, Mauro E, Baliellas C, Castells L, et al. The efficacy of direct anti-HCV drugs improves early post-liver transplant survival and induces significant changes in waiting list composition. J Hepatol. 2018;69(1):11–7. CrossRef
•• Belli LS, Perricone G, Adam R, Cortesi PA, Strazzabosco M, Facchetti R, et al. Impact of DAAs on liver transplantation: major effects on the evolution of indications and results. An ELITA study based on the ELTR registry. J Hepatol. 2018;69(4):810–7. This study presents the current epidemiologic trends for liver transplant indications with a rapid decline of OLT due to viral hepatitis C virus infection. CrossRef
Belli LS, Berenguer M, Cortesi PA, Strazzabosco M, Rockenschaub SR, Martini S, et al. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: a European study. J Hepatol. 2016;65(3):524–31. CrossRef
Perricone G, Duvoux C, Berenguer M, Cortesi PA, Vinaixa C, Facchetti R, et al. Delisting HCV-infected liver transplant candidates who improved after viral eradication: outcome 2 years after delisting. Liver Int. 2018;38:2170–7. CrossRef
Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, Brown RS Jr, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149(3):649–59. CrossRef
Manns M, Samuel D, Gane EJ, Mutimer D, McCaughan G, Buti M, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis. 2016;16(6):685–97. CrossRef
Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373(27):2618–28. CrossRef
European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018;69(2):461–511. CrossRef
Kwong AJ, Kim WR, Flemming JA. De novo hepatocellular carcinoma among liver transplant registrants in the direct acting antiviral era. Hepatology. 2018;68(4):1288–97. https://doi.org/10.1002/hep.30045.
Huang AC, Mehta N, Dodge JL, Yao FY, Terrault NA. Direct-acting antivirals do not increase the risk of hepatocellular carcinoma recurrence after local-regional therapy or liver transplant waitlist dropout. Hepatology. 2018;68(2):449–61. CrossRef
• Mauro E, Crespo G, Montironi C, Londono MC, Hernandez-Gea V, Ruiz P, et al. Portal pressure and liver stiffness measurements in the prediction of fibrosis regression after sustained virological response in recurrent hepatitis C. Hepatology. 2018;67(5):1683–94. The study showed that SVR after OLT induces fibrosis regression and assessed potential determinants for the likelihood of fibrosis regression. CrossRef
Mandorfer M, Schwabl P, Peck-Radosavljevic M, Reiberger T, Vienna HIV, Liver Study G, et al. Letter: sustained virological response and liver healing - authors’ reply. Aliment Pharmacol Ther. 2017;45(8):1173–4. CrossRef
Jacobson IM, Lim JK, Fried MW. American Gastroenterological Association Institute clinical practice update-expert review: care of patients who have achieved a sustained virologic response after antiviral therapy for chronic hepatitis C infection. Gastroenterology. 2017;152(6):1578–87. CrossRef
Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148(3):547–55. CrossRef
Unger LW, Herac M, Staufer K, Salat A, Silberhumer G, Hofmann M, et al. The post-transplant course of patients undergoing liver transplantation for nonalcoholic steatohepatitis versus cryptogenic cirrhosis: a retrospective case-control study. Eur J Gastroenterol Hepatol. 2017;29(3):309–16. CrossRef
Wong RJ, Chou C, Bonham CA, Concepcion W, Esquivel CO, Ahmed A. Improved survival outcomes in patients with non-alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002-2012 United Network for Organ Sharing data. Clin Transpl. 2014;28(6):713–21. CrossRef
• Malik SM, de Vera ME, Fontes P, Shaikh O, Ahmad J. Outcome after liver transplantation for NASH cirrhosis. Am J Transplant. 2009;9(4):782–93. While OLT for NASH in general was associated with similar post-transplant mortality as other indications but NASH patients with morbid obesity, age > 60 years, diabetes, and arterial hypertension presented a 50% risk of 1-year post-OLT mortality. CrossRef
• Vallin M, Guillaud O, Boillot O, Hervieu V, Scoazec JY, Dumortier J. Recurrent or de novo nonalcoholic fatty liver disease after liver transplantation: natural history based on liver biopsy analysis. Liver Transpl. 2014;20(9):1064–71. This work suggests that patients with recurrent NASH show a worse clinical course than patients with de novo NASH after OLT. CrossRef
Dulai PS, Singh S, Patel J, Soni M, Prokop LJ, Younossi Z, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017;65(5):1557–65. CrossRef
McPherson S, Hardy T, Henderson E, Burt AD, Day CP, Anstee QM. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol. 2015;62(5):1148–55. CrossRef
Pais R, Charlotte F, Fedchuk L, Bedossa P, Lebray P, Poynard T, et al. A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver. J Hepatol. 2013;59(3):550–6. CrossRef
Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13(4):643–54 e641–649; quiz e639–640. CrossRef
Schuppan D, Surabattula R, Wang XY. Determinants of fibrosis progression and regression in NASH. J Hepatol. 2018;68(2):238–50. CrossRef
von Schonfels W, Beckmann JH, Ahrens M, Hendricks A, Rocken C, Szymczak S, et al. Histologic improvement of NAFLD in patients with obesity after bariatric surgery based on standardized NAS (NAFLD activity score). Surg Obes Relat Dis. 2018;14(10):1607–16. https://doi.org/10.1016/j.soard.2018.07.012.
Wong VW, Wong GL, Chan RS, Shu SS, Cheung BH, Li LS, et al. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol. 2018;69(6):1349–56. https://doi.org/10.1016/j.jhep.2018.08.011.
Debette-Gratien M, Tabouret T, Antonini MT, Dalmay F, Carrier P, Legros R, et al. Personalized adapted physical activity before liver transplantation: acceptability and results. Transplantation. 2015;99(1):145–50. CrossRef
Tandon P, Ismond KP, Riess K, Duarte-Rojo A, Al-Judaibi B, Dunn MA, et al. Exercise in cirrhosis: translating evidence and experience to practice. J Hepatol. 2018;69:1164–77. CrossRef
•• Anastacio LR, Ferreira SC. Nutrition, dietary intake, and eating behavior after liver transplantation. Curr Opin Clin Nutr Metab Care. 2018;21(5):381–7. This review summarizes a broad range of recent studies on nutrition after OLT.
Bonner K, Heimbach JK. Obesity management in the liver transplant recipient: the role of bariatric surgery. Curr Opin Organ Transplant. 2018;23(2):244–9.
Lainas P, Dupond-Athenor A, Tranchart H, Dagher I. Safety and feasibility of single-port sleeve gastrectomy following liver transplantation. Obes Surg. 2018;28(3):874–6. CrossRef
• Eilenberg M, Langer FB, Beer A, Trauner M, Prager G, Staufer K. Significant liver-related morbidity after bariatric surgery and its reversal-a case series. Obes Surg. 2018;28(3):812–9. The authors of this case series demonstrated the paradox of liver dysfunction after bariatric surgery and reversal thereof by bypass lenght reduction. CrossRef
• Berzigotti A, Albillos A, Villanueva C, Genesca J, Ardevol A, Augustin S, et al. Effects of an intensive lifestyle intervention program on portal hypertension in patients with cirrhosis and obesity: the SportDiet study. Hepatology. 2017;65(4):1293–305. The authors found that a reduction in body weight is associated with a decrease of portal pressure in overweight patients after diet and moderate exercise. CrossRef
Fujiki M, Hashimoto K, Palaios E, Quintini C, Aucejo FN, Uso TD, et al. Probability, management, and long-term outcomes of biliary complications after hepatic artery thrombosis in liver transplant recipients. Surgery. 2017;162(5):1101–11. CrossRef
Lui SK, Garcia CR, Mei X, Gedaly R. Re-transplantation for hepatic artery thrombosis: a national perspective. World J Surg. 2018;42:3357–63. CrossRef
Lee H, Lim CW, Yoo SH, Koo CH, Kwon WI, Suh KS, et al. The effect of Doppler ultrasound on early vascular interventions and clinical outcomes after liver transplantation. World J Surg. 2014;38(12):3202–9. CrossRef
Rather SA, Nayeem MA, Agarwal S, Goyal N, Gupta S. Vascular complications in living donor liver transplantation at a high-volume center: evolving protocols and trends observed over 10 years. Liver Transpl. 2017;23(4):457–64. CrossRef
Ye Q, Zeng C, Wang Y, Fang Z, Hu X, Xiong Y, et al. Risk factors for hepatic venous outflow obstruction in piggyback liver transplantation: the role of recipient’s pattern of hepatic veins drainage into the inferior vena cava. Ann Transplant. 2017;22:303–8. CrossRef
Wang Y, Xin Z, Pan B, Lv SC, Zhang XM, Zhang ZH et al. Venous anastomosis using a non-penetrating vascular closure system in orthotopic liver transplantation. Clin Transpl. 2017;31(12). https://doi.org/10.1111/ctr.13123.
Pitchaimuthu M, Roll GR, Zia Z, Olliff S, Mehrzad H, Hodson J, et al. Long-term follow-up after endovascular treatment of hepatic venous outflow obstruction following liver transplantation. Transpl Int. 2016;29(10):1106–16. CrossRef
Unger LW, Matzek W, Berlakovich G. Rare late complication after percutaneous liver biopsy. Am J Transplant. 2017;17(8):2221–3. CrossRef
•• Draoua M, Titze N, Gupta A, Fernandez HT, Ramsay M, Saracino G, et al. Significance of measured intraoperative portal vein flows after thrombendvenectomy in deceased donor liver transplantations with portal vein thrombosis. Liver Transpl. 2017;23(8):1032–9. This study demonstrated significant differences in survival according to portal venous flow after thrombectomy during OLT and defined a flow > 1300 mL/min as an important cutoff predicting sufficient recanalization. CrossRef
Stine JG, Shah NL, Argo CK, Pelletier SJ, Caldwell SH, Northup PG. Increased risk of portal vein thrombosis in patients with cirrhosis due to nonalcoholic steatohepatitis. Liver Transpl. 2015;21(8):1016–21. CrossRef
•• Hibi T, Nishida S, Levi DM, Selvaggi G, Tekin A, Fan J, et al. When and why portal vein thrombosis matters in liver transplantation: a critical audit of 174 cases. Ann Surg. 2014;259(4):760–6. This study demonstrated the necessity of physiological portal vein reconstruction as compared to non-anatomical reconstruction. CrossRef
Ghabril M, Agarwal S, Lacerda M, Chalasani N, Kwo P, Tector AJ. Portal vein thrombosis is a risk factor for poor early outcomes after liver transplantation: analysis of risk factors and outcomes for portal vein thrombosis in waitlisted patients. Transplantation. 2016;100(1):126–33. CrossRef
•• Villa E, Camma C, Marietta M, Luongo M, Critelli R, Colopi S, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology. 2012;143(5):1253–60 e1251-1254. This study demonstrated that LMWH successfully prevented PVT and even improved survival in patients with cirrhosis. CrossRef
• Senzolo M, MS T, Rossetto V, Burra P, Cillo U, Boccagni P, et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis. Liver Int. 2012;32(6):919–27. This study evaluated a treatment algorithm of LMWH and TIPS implantation for the management of PVT. CrossRef
• Bianchini M, Cavani G, Bonaccorso A, Turco L, Vizzutti F, Sartini A, et al. Low molecular weight heparin does not increase bleeding and mortality post-endoscopic variceal band ligation in cirrhotic patients. Liver Int. 2018;38(7):1253–62 This study underlined the safety of LMWH in patients undergoing variceal band ligation of esophageal varices. CrossRef
La Mura V, Braham S, Tosetti G, Branchi F, Bitto N, Moia M, et al. Harmful and beneficial effects of anticoagulants in patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol. 2018;16(7):1146–52 e1144. CrossRef
Mazzarelli C, Vangeli M, Airoldi A. Reply to “Harmful and beneficial effects of anticoagulants in patients with cirrhosis and portal vein thrombosis”. Clin Gastroenterol Hepatol. 2018. https://doi.org/10.1016/j.cgh.2018.08.004.
Unger LW, Stork T, Bucsics T, Rasoul-Rockenschaub S, Staufer K, Trauner M, et al. The role of TIPS in the management of liver transplant candidates. United European Gastroenterol J. 2017;5(8):1100–7. CrossRef
Wang Z, Jiang MS, Zhang HL, Weng NN, Luo XF, Li X, et al. Is post-TIPS anticoagulation therapy necessary in patients with cirrhosis and portal vein thrombosis? A Randomized Controlled Trial. Radiology. 2016;279(3):943–51. CrossRef
Thornburg B, Desai K, Hickey R, Hohlastos E, Kulik L, Ganger D, et al. Pretransplantation portal vein recanalization and transjugular intrahepatic portosystemic shunt creation for chronic portal vein thrombosis: final analysis of a 61-patient cohort. J Vasc Interv Radiol. 2017;28(12):1714–21 e1712. CrossRef
Koh PS, Chan SC, Chok KS, Sharr WW, Wong TC, Sin SL, et al. The friendly incidental portal vein thrombus in liver transplantation. Liver Transpl. 2015;21(7):944–52. CrossRef
Qi X, Dai J, Jia J, Ren W, Yang M, Li H, et al. Association between portal vein thrombosis and survival of liver transplant recipients: a systematic review and meta-analysis of observational studies. J Gastrointestin Liver Dis. 2015;24(1):51–9 54 p following 59.
Zanetto A, Rodriguez-Kastro KI, Germani G, Ferrarese A, Cillo U, Burra P et al. Mortality in liver transplant recipients with portal vein thrombosis - an updated meta-analysis. Transpl Int. 2018;31(12):1318–29. https://doi.org/10.1111/tri.13353.
•• Reiberger T, Ulbrich G, Ferlitsch A, Payer BA, Schwabl P, Pinter M, et al. Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol. Gut. 2013;62(11):1634–41. This study demonstrated the superiority of carvedilol compared to propranolol in HVPG reduction and mortality reduction. CrossRef
Galioto A, Semplicini A, Zanus G, Fasolato S, Sticca A, Boccagni P, et al. Nifedipine versus carvedilol in the treatment of de novo arterial hypertension after liver transplantation: results of a controlled clinical trial. Liver Transpl. 2008;14(7):1020–8. CrossRef
Schepis F, Vukotic R, Berzigotti A, Carrion JA, Forns X, Abraldes JG, et al. Hemodynamic response to propranolol in patients with recurrent hepatitis C virus-related cirrhosis after liver transplantation: a case-control study. Liver Transpl. 2013;19(4):450–6. CrossRef
- Portal Hypertension after Liver Transplantation—Causes and Management
Lukas W. Unger
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