ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 5 of 50
УЖМБС 2021, 6(3): 45–52
Medicine. Reviews

Hepatopulmonary Syndrome. Review

Potii V. V. 1, Kiriienko V. T. 2, Glukhova E. I. 1, Kunickaya O. S. 1, Potii D. A. 1

Liver cirrhosis is often accompanied by complications from the pulmonary system. These include hydrothorax, portopulmonary hypertension and hepatopulmonary syndrome. Hepatic hydrothorax affects about 6-10% of patients with end-stage disease, which results in the passage of ascetic fluid into the pleural space through diaphragm defects. The common cause of the hepatopulmonary syndrome and portopulmonary hypertension is portal hypertension and portosystemic shunting, indicating that vasoactive and angiogenetic factors originating from the liver normally control the pulmonary circulation. Portopulmonary hypertension is like pulmonary arterial hypertension, which develops against the background of portal hypertension as a result of chronic liver disease or without other causes of increased pressure in the pulmonary vessels. The prevalence of portopulmonary hypertension ranges from 2% to 8.5% among patients with portal hypertension and is associated with a poor prognosis. Hepatopulmonary syndrome is characterized by intrapulmonary dilatation of microvessels, which causes intrapulmonary shunting and leads to impaired gas exchange in liver diseases, and is associated with a decrease in the quality and duration of life in patients with cirrhosis. Nitric oxide overproduction and angiogenesis seem to be the hallmarks of a complicated pathogenetic mechanism, leading to intrapulmonary shunting and ventilation-perfusion mismatch. A classification of hepatopulmonary syndrome according to the severity of hypoxemia has been suggested. Hepatopulmonary syndrome includes a triad: hepatic dysfunction and / or portal hypertension, dilatation of intrapulmonary vessels, and increased alveolar-arterial oxygen gradient. The prevalence of hepatopulmonary syndrome varies depending on the study groups from 5% to 30%. The most common symptom of the complication is shortness of breath, but in most cases, hepatopulmonary syndrome is asymptomatic. A decrease in oxygen saturation less than 96% corresponds to a decrease in PaO2<70 mm Hg and testifies to the possible development of hepatopulmonary syndrome. In the case of a positive screening, the patient should undergo arterial blood gas analysis, which helps to determine PaO2 and alveolar to arterial oxygen gradient. Conclusion. Contrast-enhanced echocardiography with agitated saline is the gold standard in the diagnosis of intrapulmonary dilatation. The only effective treatment for hepatopulmonary syndrome is liver transplantation. Complete recovery of hepatopulmonary syndrome after liver transplantation is observed within a year in most patients with cirrhosis and hepatopulmonary syndrome

Keywords: hepatopulmonary syndrome, liver cirrhosis, ventilation, perfusion, intrapulmonary vasodilation, contrast-enhanced echocardiography, liver transplantation

Full text: PDF (Rus) 309K

  1. Kennedy TC, Knudson RJ. Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis. Chest. 1977; 72: 305-309. PMid: 891282.
  2. Soulaidopoulos S, Cholongitas E, Giannakoulas G, Vlachou M, Goulis I. Review article: Update on current and emergent data on hepatopulmonary syndrome World J Gastroenterol. 2018 March 28; 24(12): 1285-1298. PMid: 29599604. PMCid: PMC5871824.
  3. Krowka MJ, Fallon MB, Kawut SM, Fuhrmann V, Heimbach JK, Ramsay MA, et al. International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation. 2016 Jul; 100(7): 1440-52. PMid: 27326810.
  4. Krowka MJ. Hepatopulmonary Syndrome and Portopulmonary Hypertension: The Pulmonary Vascular Enigmas of Liver Disease. Clin Liver Dis (Hoboken). 2020 Mar 2; 15(Suppl 1): S13-S24. PMid: 32140210. PMCid: PMC7050952.
  5. Mendoza N, Rivas E, Rodriguez-Roisin R, Garcia T, Bruguera M, Agusti A, et al. Liver epigenome changes in patients with hepatopulmonary syndrome: A pilot study. PLoS One. 2021 Feb 25; 16(2): e0245046. PMid: 33630849. PMCid: PMC7906328.
  6. Grilo I, Pascasio JM, López-Pardo FJ, Ortega-Ruiz F, Tirado JL, Sousa JM, et al. Hepatopulmonary syndrome: which blood gas analysis criteria and position should we use for diagnosis? Rev Esp Enferm Dig. 2017 Dec; 109(12): 843-849.
  7. Rojas E, Aktas A, Parikh H, Khawaja US, Pergament K. Platypnea-orthodeoxia Syndrome in a Patient with Cryptogenic Liver Cirrhosis: An Elusive Cause of Hypoxemia. Cureus. 2019 Jan 8; 11(1): e3846.
  8. Rodríguez-Roisin R, Krowka MJ, Agustí A. Hepatopulmonary Disorders: Gas Exchange and Vascular Manifestations in Chronic Liver Disease. Compr Physiol. 2018 Mar 25; 8(2): 711-729. PMid: 29687908.
  9. Campanile A, Colombo A, Del Pinto M, Cavallini C. Persistent Unexplained Dyspnea: A Case of Hepatopulmonary Syndrome. Case Rep Cardiol. 2017; 2017: 1469893. PMid: 28948051. PMCid: PMC5602492.
  10. Nishiyama SK, Zhao J, Wray DW, Richardson RS. Vascular function and endothelin-1: tipping the balance between vasodilatation and vasoconstriction. J Appl Physiol. 2017; 122: 354-60. PMid: 27909229. PMCid: PMC5338602.
  11. Gao WZ, Yang YH, Dan L, Zhu XW. Splenic tyrosine kinase promotes pulmonary angiogenesis in rats with hepatopulmonary syndrome. Sheng Li Xue Bao. 2020 Dec 25; 72(6): 785-792.
  12. Li X, Chen Y, Chang Y, Li S, Zhao Z, Zhang H. CXCR2 is involved in pulmonary intravascular macrophage accumulation and angiogenesis in a rat model of hepatopulmonary syndrome. Clin Sci (Lond). 2017 Jan 1; 131(2): 159-168. PMid: 27879294.
  13. Krowka MJ. The liver-lung vascular connection. BRN Rev. 2017; 23: 204-219.
  14. Sendra C, Carballo-Rubio V, Sousa JM. Hepatopulmonary Syndrome and Portopulmonary Hypertension: Management in Liver Transplantation in the Horizon 2020. Transplant Proc. 2020 Jun; 52(5): 1503-1506. PMid: 32278579.
  15. Benz F, Mohr R, Tacke F, Roderburg C. Pulmonary Complications in Patients with Liver Cirrhosis. J Transl Int Med. 2020 Sep 25; 8(3): 150-158. PMid: 33062591. PMCid: PMC7534492.
  16. Palma DT, Philips GM, Arguedas MR, Harding SM, Fallon MB. Oxygen desaturation during sleep in hepatopulmonary syndrome. Hepatology. 2008; 47: 1257-1263. PMid: 18311748.
  17. Raevens S, Rogiers X, Geerts A, Verhelst X, Samuel U, van Rosmalen M, et al. Outcome of liver transplantation for hepatopulmonary syndrome: A Eurotransplant experience. Eur Respir J. 2019; 53: 180-196.
  18. Aller R, Moya JL, Moreira V, Boixeda D, Cano A, Picher J, et al. Diagnosis of hepatopulmonary syndrome with contrast transesophageal echocardiography: advantages over contrast transthoracic echocardiography. Dig Dis Sci. 1999; 44: 1243-1248. PMid: 10389704.
  19. Weinfurtner K, Forde K. Hepatopulmonary Syndrome and Portopulmonary Hypertension: Current Status and Implications for Liver Transplantation. Curr Hepatol Rep. 2020 Sep; 19(3): 174-185. PMid: 32905452.
  20. Sonavane AD, Bagde A, Raut V, Marar S, Sawant A, Shah K, et al. Therapeutic coil embolization of dominant shunt in hepatopulmonary syndrome enhances post-liver transplant respiratory recovery. Pediatr Transplant. 2020 Sep; 24(6): e13729. PMid: 32436643.
  21. Soulaidopoulos S, Goulis I, Cholongitas E. Pulmonary manifestations of chronic liver disease: a comprehensive review. Ann Gastroenterol. 2020 May-Jun; 33(3): 237-249. PMid: 32382226. PMCid: PMC7196609.
  22. Gupta LB, Kumar A, Jaiswal AK, Yusuf J, Mehta V, Tyagi S, et al. Pentoxifylline therapy for hepatopulmonary syndrome: a pilot study. Arch Intern Med. 2008; 168: 1820-1823. PMid: 18779471.
  23. Söderman C, Juhlin-Dannfelt A, Lagerstrand L, Eriksson LS. Ventilation-perfusion relationships and central haemodynamics in patients with cirrhosis. Effects of a somatostatin analogue. J Hepatol. 1994; 21: 52-57.
  24. Song JY, Choi JY, Ko JT, Bae EJ, Kim HS, Noh CI, et al. Long-term aspirin therapy for hepatopulmonary syndrome. Pediatrics. 1996; 97: 917-920.