Hepatopulmonary syndrome (HPS) is a common pulmonary complication of advanced liver disease. The disturbance of pulmonary ventilation/blood perfusion due to intrapulmonary vascular dilatations on the basis of acute/chronic liver disease or portal hypertension leads to dyspnea and hypoxemia. The early diagnosis rate of HPS is low, and the treatment is limited, which seriously affects the survival rate and quality of life of patients. In this article, we summary  pathogenesis, clinical manifestations, diagnosis and treatment progress of HPS, in order to improve the clinical understanding and diagnosis level of HPS.

1.Kennedy TC, Knudson RJ. Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis[J]. Chest, 1977, 72(3): 305-309. DOI: 10.1378/chest.72.3.305.

2.Weinfurtner K, Forde K. Hepatopulmonary syndrome and portopulmonary hypertension: current status and implications for liver transplantation[J]. Curr Hepatol Rep, 2020, 19(3): 174-185. DOI: 10.1007/s11901-020-005 32-y.

3.Noli K, Solomon M, Golding F, et al. Prevalence of hepatopulmonary syndrome in children[J]. Pediatrics, 2008, 121(3): e522-527. DOI: 10.1542/peds.2007-1075.

4.Warner S, McKiernan PJ, Hartley J, et al. Hepatopulmonary syndrome in children: a 20-year review of presenting symptoms, clinical progression, and transplant outcome[J]. Liver Transpl, 2018, 24(9): 1271-1279. DOI: 10.1002/lt. 25296.

5.Cartin-Ceba R, Krowka MJ. Pulmonary complications of portal hypertension[J]. Clin Liver Dis, 2019, 23(4): 683-711. DOI: 10.1016/j.cld.2019.06.003.

6.Fallon MB, Krowka MJ, Brown RS, et al. Impact of hepatopulmonary syndrome on quality of life and survival in liver transplant candidates[J]. Gastroenterology, 2008, 135(4): 1168-1175. DOI: 10.1053/j.gastro.2008.06.038.

7.Borkar VV, Poddar U, Kapoor A, et al. Hepatopulmonary syndrome in children: a comparative study of non-cirrhotic vs. cirrhotic portal hypertension[J]. Liver Int, 2015, 35(6): 1665-1672. DOI: 10.1111/liv.12708.

8.Machicao VI, Balakrishnan M, Fallon MB. Pulmonary complications in chronic liver disease[J]. Hepatology, 2014, 59(4): 1627-1637. DOI: 10.1002/hep.26745.

9.Pandey S, Sood V, Khanna R, et al. Natural history, risk factors, and outcome of hepatopulmonary syndrome in pediatric liver diseases[J]. Indian J Gastroenterol, 2020, 39(1): 66-74. DOI: 10.1007/s12664-020-01015-0.

10.Khiangte B, Kothakota SR, Sasidharan M, et al. Prevalence and determinants of hepatopulmonary syndrome in decompensated chronic liver disease[J]. Indian J Gastroenterol, 2020, 39(4): 362-369. DOI: 10.1007/s126 64-020-01052-9.

11.Gu HJ, Zuo S, Liu HY, et al. CX3CR1 participates in pulmonary angiogenesis in experimental hepatopulmonary syndrome mice through inhibiting AKT/ERK signaling pathway and regulating NO/NOS release[J]. Eur Rev Med Pharmacol Sci, 2019, 23(15): 6645-6656. DOI: 10.26355/eurrev_201908_18555.

12.Rolla G, Brussino L, Colagrande P, et al. Exhaled nitric oxide and impaired oxygenation in cirrhotic patients before and after liver transplantation[J]. Ann Intern Med, 1998, 129(5): 375-378. DOI: 10.7326/0003-4819-129-5-1998 09010-00005.

13.Zhang J, Luo B, Tang L, et al. Pulmonary angiogenesis in a rat model of hepatopulmonary syndrome[J]. Gastroenterology, 2009, 136(3): 1070-1080. DOI: 10.105 3/j.gastro.2008.12.001.

14.Chen Y, Yang C, Li Y, et al. MiR145-5p inhibits proliferation of PMVECs via PAI-1 in experimental hepatopulmonary syndrome rat pulmonary microvascular hyperplasia[J]. Biol Open, 2019, 8(11): bio044800. DOI: 10.1242/bio.044800.

15.Chen L, Han Y, Li Y, et al. Hepatocyte-derived exosomal MiR-194 activates PMVECs and promotes angiogenesis in hepatopulmonary syndrome[J]. Cell Death Dis, 2019, 10(11): 853. DOI: 10.1038/s41419-019-2087-y.

16.Raevens S, Geerts A, Paridaens A, et al. Placental growth factor inhibition targets pulmonary angiogenesis and represents a therapy for hepatopulmonary syndrome in mice[J]. Hepatology, 2018, 68(2): 634-651. DOI: 10.1002/hep.29579.

17.Low ES, Patwala K, Apostolov R. Dyspnoea, clubbing, cirrhosis, and bubbles in both sides of the heart suggests hepatopulmonary syndrome[J]. Lancet, 2019, 394(10197): 510. DOI: 10.1016/s0140-6736(19)31720-9.

18.Krowka MJ, Fallon MB, Kawut SM, et al. International liver transplant society practice guidelines: diagnosis and management of hepatopulmonary syndrome and portopulmonary hypertension[J]. Transplantation, 2016, 100(7): 1440-1452. DOI: 10.1097/tp.0000000000001229.

19.Olsson KM, Meyer K, Berliner D, et al. Development of hepatopulmonary syndrome during combination therapy for portopulmonary hypertension[J]. Eur Respir J, 2019, 53(1): 1801880. DOI: 10.1183/13993003.01880-2018.

20.Iqbal S, Smith KA, Khungar V. Hepatopulmonary syndrome and portopulmonary hypertension: implications for liver transplantation[J]. Clin Chest Med, 2017, 38(4): 785-795. DOI: 10.1016/j.ccm.2017.08.002.

21.Hoerning A, Raub S, Neudorf U, et al. Pulse oximetry is insufficient for timely diagnosis of hepatopulmonary syndrome in children with liver cirrhosis[J]. J Pediatr, 2014, 164(3): 546-552.e1-e2. DOI: 10.1016/j.jpeds. 2013.10.070.

22.Forde KA, Fallon MB, Krowka MJ, et al. Pulse oximetry is insensitive for detection of hepatopulmonary syndrome in patients evaluated for liver transplantation[J]. Hepatology, 2019, 69(1): 270-281. DOI: 10.1002/hep.30139.

23.Raevens S, Boret M, De Pauw M, et al. Pulmonary abnormalities in liver disease: relevance to transplantation and outcome[J]. Hepatology, 2021, 74(3): 1674-1686. DOI: 10.1002/hep.31770.

24.Turine Neto P, Seda Neto J, da Fonseca EA, et al. Impact of hypoxemia on pediatric liver transplantation for hepatopulmonary syndrome[J]. Pediatr Transplant, 2021, 25(5): e13968. DOI: 10.1111/petr.13968.

25.Russell-Jones E, Grammatikopoulos T, Greenough A, et al. Non-invasive assessment of intrapulmonary shunt and ventilation to perfusion ratio in children with hepatopulmonary syndrome before and after liver transplantation[J]. Respir Med, 2021, 180: 106372. DOI: 10.1016/j.rmed.2021.106372.

26.Abrams GA, Jaffe CC, Hoffer PB, et al. Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome[J]. Gastroenterology, 1995, 109(4): 1283-1288. DOI: 10.101 6/0016-5085(95)90589-8.

27.European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis[J]. J Hepatol, 2018, 69(2): 406-460. DOI: 10.101 6/j.jhep.2018.03.024.

28.Zhao H, Tsauo J, Zhang XW, et al. Technetium-99m-labeled macroaggregated albumin lung perfusion scan for diagnosis of hepatopulmonary syndrome: a prospective study comparing brain uptake and whole-body uptake[J]. World J Gastroenterol, 2020, 26(10): 1088-1097. DOI: 10.3748/wjg.v26.i10.1088.

29.Martinez G, Barberà JA, Navasa M, et al. Hepatopulmonary syndrome associated with cardiorespiratory disease[J]. J Hepatol, 1999, 30(5): 882-889. DOI: 10.1016/s0168-8278(99)80143-3.

30.Raevens S, Geerts A, Devisscher L, et al. Recent advances in the approach to hepatopulmonary syndrome and portopulmonary hypertension[J]. Acta Gastroenterol Belg, 2021, 84(1): 95-99. DOI: 10.51821/84.1.200.

31.Horvatits T, Drolz A, Roedl K, et al. Von Willebrand factor antigen for detection of hepatopulmonary syndrome in patients with cirrhosis[J]. J Hepatol, 2014, 61(3): 544-549. DOI: 10.1016/j.jhep.2014.04.025.

32.Darmadi D, Ruslie RH. Endothelin-1 level as a predictor of hepatopulmonary syndrome in liver cirrhosis[J]. Med Glas (Zenica), 2020, 17(2): 389-394. DOI: 10.1739 2/1177-20.

33.Nanchal R, Subramanian R, Karvellas CJ, et al. Guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU: cardiovascular, endocrine, hematologic, pulmonary, and renal considerations[J]. Crit Care Med, 2020, 48(3): e173-e191. DOI: 10.1097/ccm.0000000000004192.

34.Tsauo J, Zhao H, Zhang X, et al. Changes in arterial oxygenation after portal decompression in Budd-Chiari syndrome patients with hepatopulmonary syndrome[J]. Eur Radiol, 2019, 29(6): 3273-3280. DOI: 10.1007/s00330-018-5840-1.

35.Tsauo J, Zhao H, Zhang X, et al. Effect of transjugular intrahepatic portosystemic shunt creation on pulmonary gas exchange in patients with hepatopulmonary syndrome: a prospective study[J]. J Vasc Interv Radiol, 2019, 30(2): 170-177. DOI: 10.1016/j.jvir.2018.09.017.

36.Sonavane AD, Bagde A, Raut V, et al. Therapeutic coil embolization of dominant shunt in hepatopulmonary syndrome enhances post-liver transplant respiratory recovery[J]. Pediatr Transplant, 2020, 24(6): e13729. DOI: 10.1111/petr.13729.

37.Fallon MB, Mulligan DC, Gish RG, et al. Model for end-stage liver disease (MELD) exception for hepatopulmonary syndrome[J]. Liver Transpl, 2006, 12(12 Suppl 3): S105-107. DOI: 10.1002/lt.20971.

38.Goldberg DS, Krok K, Batra S, et al. Impact of the hepatopulmonary syndrome MELD exception policy on outcomes of patients after liver transplantation: an analysis of the UNOS database[J]. Gastroenterology, 2014, 146(5): 1256-1265.e1. DOI: 10.1053/j.gastro.2014.01.005.

39.Kim KY, Kim TH, Lee JM, et al. Clinical outcomes and risk factors of hepatopulmonary syndrome in children[J]. Sci Rep, 2021, 11(1): 4134. DOI: 10.1038/s41598-021-83785-x.

40.Sendra C, Carballo-Rubio V, Sousa JM. Hepatopulmonary syndrome and portopulmonary hypertension: management in liver transplantation in the horizon 2020[J]. Transplant Proc, 2020, 52(5): 1503-1506. DOI: 10.1016/j.trans proceed.2020.02.057.

41.Nayyar D, Man HS, Granton J, et al. Proposed management algorithm for severe hypoxemia after liver transplantation in the hepatopulmonary syndrome[J]. Am J Transplant, 2015, 15(4): 903-913. DOI: 10.1111/ajt.13177.

42.Gupta S, Tang R, Al-Hesayen A. Inhaled nitric oxide improves the hepatopulmonary syndrome: a physiologic analysis[J]. Thorax, 2021, 76(11): 1142-1145. DOI: 10.1136/thoraxjnl-2020-216128.