Hepatopulmonary syndrome
an update
Keywords:
Hepatopulmonary syndrome, Liver transplantation, Liver cirrhosis, Hypertension, portal, Echocardiography, Liver cirrhosis, experimentalAbstract
Hepatopulmonary syndrome (HPS) is a clinical threesome composed of liver disease, intrapulmonary vascular dilatation (IPVD) and arterial gas abnormalities. Its occurrence has been described in up to 32% of cirrhotic candidates for liver transplantation. It also affects non-cirrhotic patients with portal hypertension. Its pathogenesis is not well defined, but an association of factors such as imbalance in the endothelin receptor response, pulmonary microvascular remodeling and genetic predisposition is thought to lead to IPVD. Diagnosis is based on imaging methods that identify these dilatations, such as contrast echocardiography or perfusion scintigraphy with 99mTc, as well as analysis of arterial gases to identify elevated alveolar-arterial differences in O2 or hypoxemia. There is no effective pharmacological treatment and complete resolution only occurs through liver transplantation. The importance of diagnosing HPS lies in prioritizing transplant candidates, since presence of HPS is associated with worse prognosis. The aim of this paper was to review the pathogenetic theories and current diagnostic criteria regarding HPS, and to critically analyze the prioritization of patients with HPS on the liver transplant waiting list. Searches were carried out in the Medline (Medical Literature Analysis and Retrieval System Online) via PubMed, Cochrane Library and Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) databases for articles published between January 2002 and December 2007 involving adults and written either in English or in Portuguese, using the term hepatopulmonary syndrome. The studies of greatest relevance were included in the review, along with text books and articles cited in references that were obtained through the review.
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References
Krowka MJ, Cortese DA. Hepatopulmonary syndrome. Current concepts in diagnostic and therapeutic considerations. Chest. 1994;105(5):1528-37.
Kennedy TC, Knudson RJ. Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis. Chest. 1977;72(3):305-9.
Abrams GA, Sanders MK, Fallon MB. Utility of pulse oximetry in the detection of arterial hypoxemia in liver transplant candidates. Liver Transpl. 2002;8(4):391-6.
Fallon MB, Abrams GA. Pulmonary dysfunction in chronic liver disease. Hepatology. 2000;32(4 Pt 1):859-65.
Rodríguez-Roisin R, Krowka MJ, Hervé P, Fallon MB; ERS Task Force Pulmonary-Hepatic Vas- cular Disorders (PHD) Scientific Committee. Pulmonary-Hepatic vascular Disorders (PHD). Eur Respir J. 2004;24(5):861-80.
Krowka MJ. Hepatopulmonary syndrome and portopulmonary hypertension: implications for liver transplantation. Clin Chest Med. 2005;26(4):587-97, vi.
Mandell MS. Clinical controversies surrounding the diagnosis and treatment of hepatopul- monary syndrome. Minerva Anestesiol. 2007;73(6):347-55.
Przybyłowski T, Krenke R, Fangrat A, et al. Gas exchange abnormalities in patients listed for liver transplantation. J Physiol Pharmacol. 2006;57(Suppl 4):313-23.
Schenk P, Fuhrmann V, Madl C, et al. Hepatopulmonary syndrome: prevalence and predic- tive value of various cut offs for arterial oxygenation and their clinical consequences. Gut. 2002;51(6):853-9.
Parolin MB, Coelho JC, Puccinelli V, Schulz GJ, de Souza AM, de Barros JA. Prevalência da síndrome hepatopulmonar em candidatos a transplante hepático [Hepatopulmonary syn- drome in liver transplantation candidates]. Arq Gastroenterol. 2002;39(1):11-6.
Lima BL, França AV, Pazin-Filho A, et al. Frequency, clinical characteristics, and respiratory parameters of hepatopulmonary syndrome. Mayo Clin Proc. 2004;79(1):42-8.
Freire R, Mangualde J, Vieira AM, et al. Síndrome hepatopulmonar em doentes com cirrose hepática: importância da sua pesquisa sistemática e impacto no prognóstico. J Port Gas- trenterol. 2007;14:176-83.
Swanson KL, Wiesner RH, Krowka MJ. Natural history of hepatopulmonary syndrome: Impact of liver transplantation. Hepatology. 2005;41(5):1122-9.
Arguedas MR, Abrams GA, Krowka MJ, Fallon MB. Prospective evaluation of outcomes and predictors of mortality in patients with hepatopulmonary syndrome undergoing liver trans- plantation. Hepatology. 2003;37(1):192-7.
Manzerbeitia C. Liver transplantation. eMedicine Journal. Available from: http://emedicine. medscape.com/article/431783-overview. Accessed in 2009 (Ago 12).
Marroni CA, Brandão ABM, Zanotelli ML, Cantisani GPC. Transplante hepático em adultos [Hepatic transplantation in adults]. Revista AMRIGS. 2003;47(1):29-37. Available from: http://www.amrigs.com.br/revista/47-01/Transplante%20hepático%20em%20adultos.pdf. Accessed in 2009 (Aug 12).
Sette Jr H, Barros MFA, Cury RA, Lopes Neto EPA, Pessôa MG. Transplante hepático: política de alocação de órgãos. In: Lopes AC, editor. Tratado de clínica médica. São Paulo: Roca; 2006. p. 1495-504.
United States Department of Health & Human Services. Welcome to the 2006 OPTN/SRTR Annual Report: Transplant Data 1996-2005. The U.S. Organ Procurement and Transplanta- tion Network and the Scientific Registry of Transplant Recipients. Available from: http://www.ustransplant.org/annual_reports/archives/2006/default.htm. Accessed in 2009 (Aug 12).
Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124(1):91-6.
Wiesner RH, McDiarmid SV, Kamath PS, et al. MELD and PELD: application of survival mo- dels to liver allocation. Liver Transpl. 2001;7(7):567-80.
Roberts JP, Dykstra DM, Goodrich NP, Rush SH, Merion RM, Port FK. Geographic di- fferences in event rates by model for end-stage liver disease score. Am J Transplant. 2006;6(10):2470-5.
Brasil. Ministério da Saúde. Portaria no 1.160 de 29 de maio de 2006. Modifica os critérios de distribuição de fígado de doadores cadáveres para transplante, implantando o critério de gravidade de estado clínico do paciente. Available from: http://dtr2001.saude.gov.br/sas/PORTARIAS/Port2006/GM/GM-1160.htm. Accessed in 2009 (Aug 12).
Brandão ABM, Marroni CA, Fleck Jr AM, Mariante Neto G. Cirrose. In: Lopes AC, editor. Trata- do de clínica médica. São Paulo: Roca; 2006. p. 1344-7.
Barbosa WF, Kondo M. Alterações vasculares pulmonares na hipertensão porta. Revista Virtual SOCESP. Available from: http://www.socesp.org.br/frameset.asp?destino=http://200.220.14.51/revistasocesp/index1.asp. Accessed in 2009 (Aug 12).
Strauss E. Hipertensão porta. In: Lopes AC, editor. Tratado de clínica médica. São Paulo: Roca; 2006. p. 1376-85.
Ferraz AAB, Ferraz EM. Esquistossomose. In: Lopes AC, editor. Tratado de clínica médica. São Paulo: Roca; 2006. p. 1448-57.
Domingues ALC, Silva G. Esquistossomose. In: Filgueira NA, Costa Júnior JI, Lucena VG, et al., editors. Condutas em clínica médica. 4a ed. Rio de Janeiro: Guanabara Koogan; 2007. p. 594-603.
Krasinskas AM, Eghtesad B, Kamath PS, Demetris AJ, Abraham SC. Liver transplantation for severe intrahepatic noncirrhotic portal hypertension. Liver Transpl. 2005;11(6):627-34; discussion 610-1.
Kaymakoglu S, Kahraman T, Kudat H, et al. Hepatopulmonary syndrome in noncirrhotic portal hypertensive patients. Dig Dis Sci. 2003;48(3):556-60.
De BK, Sen S, Sanyal R. Hepatopulmonary syndrome in noncirrhotic portal hypertension. Ann Intern Med. 2000;132(11):924.
Teuber G, Teupe C, Dietrich CF, Caspary WF, Buhl R, Zeuzem S. Pulmonary dysfunction in non-cirrhotic patients with chronic viral hepatitis. Eur J Intern Med. 2002;13(5):311-18.
Fuhrmann V, Madl C, Mueller C, et al. Hepatopulmonary syndrome in patients with hypoxic hepatitis. Gastroenterology. 2006;131(1):69-75.
Varghese J, Ilias-basha H, Dhanasekaran R, Singh S, Venkataraman J. Hepatopulmonary syndrome - past to present. Ann Hepatol. 2007;6(3):135-42.
Martínez-Palli G, Gómez FP, Barberà JA, et al. Sustained low diffusing capacity in hepa- topulmonary syndrome after liver transplantation. World J Gastroenterol. 2006;12(36): 5878-83.
Gómez FP, Barberà JA, Roca J, Burgos F, Gistau C, Rodríguez-Roisin R. Effects of nebulized N(G)-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome. Hepatology. 2006;43(5):1084-91.
Tieppo J, Vercelino R, Dias AS, Marroni CA, Marroni N. Ligadura de ducto biliar como mo- delo de estudo da síndrome hepatopulmonar e estresse oxidativo [Common bile duct li- gation as a model of hepatopulmonary syndrome and oxidative stress]. Arq Gastroenterol. 2005;42(4):244-8.
Luo B, Liu L, Tang L, Zhang J, Ling Y, Fallon MB. ET-1 and TNF-alpha in HPS: analysis in prehepatic portal hypertension and biliary and nonbiliary cirrhosis in rats. Am J Physiol Gastrointest Liver Physiol. 2004;286(2):G294-303.
Zhang HY, Han DW, Wang XG, Zhao YC, Zhou X, Zhao HZ. Experimental study on the role of endotoxin in the development of hepatopulmonary syndrome. World J Gastroenterol. 2005;11(4):567-72.
Luo B, Abrams GA, Fallon MB. Endothelin-1 in the rat bile duct ligation model of hepatopul- monary syndrome: correlation with pulmonary dysfunction. J Hepatol. 1998;29(4):571-8.
Filep JG. Endothelin peptides: biological actions and pathophysiological significance in the lung. Life Sci. 1993;52(2):119-33.
Vaughan RB, Angus PW, Chin-Dusting JP. Evidence for altered vascular responses to exo- genous endothelin-1 in patients with advanced cirrhosis with restoration of the normal vasoconstrictor response following successful liver transplantation. Gut. 2003;52(10): 1505-10.
Fallon MB. Mechanisms of pulmonary vascular complications of liver disease: hepatopul- monary syndrome. J Clin Gastroenterol. 2005;39(4 Suppl 2):S138-42.
Arguedas MR, Drake BB, Kapoor A, Fallon MB. Carboxyhemoglobin levels in cirrhotic patients with and without hepatopulmonary syndrome. Gastroenterology. 2005;128(2):328-33.
West JB. Fisiologia respiratória. 6a ed. São Paulo: Manole; 2002.
Chakraborty S, Balakotaiah V, Bidani A. Multiscale model for pulmonary oxygen uptake and its application to quantify hypoxemia in hepatopulmonary syndrome. J Theor Biol. 2007;244(2):190-207.
Hira HS, Kumar J, Tyagi SK, Jain SK. A study of hepatopulmonary syndrome among patients of cirrhosis of liver and portal hypertension. Indian J Chest Dis Allied Sci. 2003;45(3):165-71.
Collisson EA, Nourmand H, Fraiman MH, et al. Retrospective analysis of the results of liver transplantation for adults with severe hepatopulmonary syndrome. Liver Transpl. 2002;8(10):925-31.
Stoller JK, Lange PA, Westveer MK, Carey WD, Vogt D, Henderson JM. Prevalence and rever- sibility of the hepatopulmonary syndrome after liver transplantation. The Cleveland Clinic experience. West J Med. 1995;163(2):133-8.
Zamirian M, Aslani A, Shahrzad S. Left atrial volume: a novel predictor of hepatopulmonary syndrome. Am J Gastroenterol. 2007;102(7):1392-6.
Martínez GP, Barberà JA, Visa J, et al. Hepatopulmonary syndrome in candidates for liver transplantation. J Hepatol. 2001;34(5):651-7.
Deibert P, Allgaier H, Loesch S, et al. Hepatopulmonary syndrome in patients with chronic liver disease: role of pulse oximetry. BMC Gastroenterol. 2006;6:15.
Arguedas MR, Singh H, Faulk DK, Fallon MB. Utility of pulse oximetry screening for hepato- pulmonary syndrome. Clin Gastroenterol Hepatol. 2007;5(6):749-54.
Roberts DN, Arguedas MR, Fallon MB. Cost-effectiveness of screening for hepatopulmonary syndrome in liver transplant candidates. Liver Transpl. 2007;13(2):206-14.
Gómez FP, Martínez-Pallí G, Barberà JA, Roca J, Navasa M, Rodríguez-Roisin R. Gas exchange mechanism of orthodeoxia in hepatopulmonary syndrome. Hepatology. 2004;40(3):660-6.
Naeije R. Hepatopulmonary syndrome and portopulmonary hypertension. Swiss Med Wkly. 2003;133(11-12):163-9.
Charalabopoulos K, Peschos D, Zoganas L, et al. Alterations in arterial blood parameters in patients with liver cirrhosis and ascites. Int J Med Sci. 2007;4(2):94-7.
Aller R, Moya JL, Avila S, et al. Implications of estradiol and progesterone in pulmonary vasodilatation in cirrhotic patients. J Endocrinol Invest. 2002;25(1):4-10.
Mazzeo AT, Bottari G, Praticò C, Penna O, Mandolfino T, Santamaria LB. Significance of hy- poxemia screening in candidates for liver transplantation: our experience. Transplant Proc. 2006;38(3):793-4.
Schiffer E, Majno P, Mentha G, et al. Hepatopulmonary syndrome increases the postopera- tive mortality rate following liver transplantation: a prospective study in 90 patients. Am J Transplant. 2006;6(6):1430-7.
Stickland MK, Welsh RC, Haykowsky MJ, et al. Intra-pulmonary shunt and pulmonary gas exchange during exercise in humans. J Physiol. 2004;561(Pt 1):321-9.
Hervé P, Lebrec D, Brenot F, et al. Pulmonary vascular disorders in portal hypertension. Eur Respir J. 1998;11(5):1153-66.
Abrams GA, Jaffe CC, Hoffer PB, Binder HJ, Fallon MB. Diagnostic utility of contrast echocar- diography and lung perfusion scan in patients with hepatopulmonary syndrome. Gastroen- terology. 1995;109(4):1283-8.
Krowka MJ, Wiseman GA, Burnett OL, et al. Hepatopulmonary syndrome: a prospective study of relationships between severity of liver disease, PaO(2) response to 100% oxygen, and brain uptake after (99m)Tc MAA lung scanning. Chest. 2000;118(3):615-24.
Lange PA, Stoller JK. The hepatopulmonary syndrome. Ann Intern Med. 1995;122(7): 521-9.
Lee DF, Lepler LS. Severe intrapulmonary shunting associated with metastatic carcinoid. Chest. 1999;115(4):1203-7.
Köksal D, Kaçar S, Köksal AS, et al. Evaluation of intrapulmonary vascular dilatations with high-resolution computed thorax tomography in patients with hepatopulmonary syndrome. J Clin Gastroenterol. 2006;40(1):77-83.
Engelke C, Schaefer-Prokop C, Schirg E, Freihorst J, Grubnic S, Prokop M. High-resolu- tion CT and CT angiography of peripheral pulmonary vascular disorders. Radiographics. 2002;22(4):739-64.
Malagari K, Nikita A, Alexopoulou E, et al. Cirrhosis-related intrathoracic disease. Imaging features in 1038 patients. Hepatogastroenterology. 2005;52(62):558-62.
Frazin LJ. Patent foramen ovale or pulmonary arteriovenous malformation: an appeal for diagnostic accuracy. Chest. 2007;132(1):5-6.
Vedrinne JM, Duperret S, Bizollon T, et al. Comparison of transesophageal and transthoracic contrast echocardiography for detection of an intrapulmonary shunt in liver disease. Chest. 1997;111(5):1236-40.
Aller R, Moya JL, Moreira V, et al. Diagnosis of hepatopulmonary syndrome with contrast transesophageal echocardiography: advantages over contrast transthoracic echocardiogra- phy. Dig Dis Sci. 1999;44(6):1243-8.
Pavarino PR, Corbucci HA, Marchi CH, Mata PF, Godoy MF. A ecocardiografia com contraste no diagnóstico de dilatações vasculares intrapulmonares em candidatos ao transplante hepático [Contrast echocardiography in the diagnosis of intrapulmonary vascular dilations in patients eligible for liver transplantation]. Arq Bras Cardiol. 2004;82(4):327-36.
Madala D, Zaroff JG, Hourigan L, Foster E. Harmonic imaging improves sensitivity at the expense of specificity in the detection of patent foramen ovale. Echocardiography. 2004;21(1):33-6.
Clarke NR, Timperley J, Kelion AD, Banning AP. Transthoracic echocardiography using second harmonic imaging with Valsalva manoeuvre for the detection of right to left shunts. Eur J Echocardiogr. 2004;5(3):176-81.
Santa-Cruz RA, Pearson MD, Cohen MG, et al. Clinical predictors and characteristics of patients with chronic liver disease and intrapulmonary shunts. Clin Cardiol. 2005;28(9): 437-41.
Kim BJ, Lee SC, Park SW, et al. Characteristics and prevalence of intrapulmonary shunt de- tected by contrast echocardiography with harmonic imaging in liver transplant candidates. Am J Cardiol. 2004;94(4):525-8.
Daniëls C, Weytjens C, Cosyns B, et al. Second harmonic transthoracic echocardiography: the new reference screening method for the detection of patent foramen ovale. Eur J Echo- cardiogr. 2004;5(6):449-52.
Karabulut A, Iltumur K,Yalcin K,Toprak N. Hepatopulmonary syndrome and right ventricular dias- tolic functions: an echocardiographic examination. Echocardiography. 2006;23(4):271-8.
Martinez G, Barberà JA, Navasa M, Roca J, Visa J, Rodriguez-Roisin R. Hepatopulmonary syndrome associated with cardiorespiratory disease. J Hepatol. 1999;30(5):882-9.
Faresin SM. Avaliação pré-operatória pulmonar. Rio de Janeiro: Revinter; 2005.
Prediletto R, Catapano G, Bottai M, et al. Role of the chest radiograph in the preoperative assessment of the pulmonary function in patients with cirrhosis candidates to liver trans- plant. Radiol Med. 2004;108(4):320-34.
Martinez-Palli G, Drake BB, Garcia-Pagan JC, et al. Effect of transjugular intrahepatic por- tosystemic shunt on pulmonary gas exchange in patients with portal hypertension and he- patopulmonary syndrome. World J Gastroenterol. 2005;11(43):6858-62.
Schenk P, Madl C, Rezaie-Majd S, Lehr S, Müller C. Methylene blue improves the hepatopul- monary syndrome. Ann Intern Med. 2000;133(9):701-6.
Krowka MJ, Dickson ER, Cortese DA. Hepatopulmonary syndrome. Clinical observations and lack of therapeutic response to somatostatin analogue. Chest. 1993;104(2):515-21.
De BK, Sen S, Biswas PK, et al. Occurrence of hepatopulmonary syndrome in Budd- Chiari syndrome and the role of venous decompression. Gastroenterology. 2002;122(4): 897-903.
Poterucha JJ, Krowka MJ, Dickson ER, Cortese DA, Stanson AW, Krom RA. Failure of hepa- topulmonary syndrome to resolve after liver transplantation and successful treatment with embolotherapy. Hepatology. 1995;21(1):96-100.
Krowka MJ, Mandell MS, Ramsay MA, et al. Hepatopulmonary syndrome and portopul- monary hypertension: a report of the multicenter liver transplant database. Liver Transpl. 2004;10(2):174-82.
Carey EJ, Douglas DD, Balan V, et al. Hepatopulmonary syndrome after living donor liver transplantation and deceased donor liver transplantation: a single-center experience. Liver Transpl. 2004;10(4):529-33.
Taillé C, Cadranel J, Bellocq A, et al. Liver transplantation for hepatopulmonary syndrome: a ten-year experience in Paris, France. Transplantation. 2003;75(9):1482-9; discussion 1446-7.
Schenk P, Schöniger-Hekele M, Fuhrmann V, Madl C, Silberhumer G, Müller C. Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis. Gastroenterology. 2003;125(4):1042-52.
Mohamed R, Freeman JW, Guest PJ, Davies MK, Neuberger JM. Pulmonary gas exchange abnormalities in liver transplant candidates. Liver Transpl. 2002;8(9):802-8.
Levitsky J, McCashland T. Hepatopulmonary syndrome. In: Reddy KR, Faust T, editors. The clinician’s guide to liver disease. United States of America: Slack Incorporated; 2006. p. 271-82.
Leyva EM, Zepeda VHJ, Alonso LAG, Martínez IA. Síndrome hepatopulmonar. Anales Medicos. 2006;51(3):124-33. Available from: http://www.medigraphic.com/espanol/e-htms/e-abc/e-bc2006/e-bc06-3/em-bc063e.htm. Accessed in 2009 (Aug 12).
Kim HY, Choi MS, Lee SC, et al. Outcomes in patients with hepatopulmonary syndrome undergoing liver transplantation. Transplant Proc. 2004;36(9):2762-3.
Fernandes JH, Millan LS, Massarollo PCB, Mies S. Efeito da escala MELD na mortalidade após transplante de fígado [The effect of MELD on the post liver transplantation mortality rate]. Rev Med (São Paulo). 2002;81(1/4):15-21.
