Skip to main content

Advertisement

SpringerLink
Log in

Hepatopulmonary syndrome is related to the development of acute-on-chronic liver failure and poor prognosis in cirrhotic patients

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Background and aims

Long-term prospective data on hepatopulmonary syndrome (HPS) from a large number of patients, especially in Asian patients, are lacking. We evaluated the long-term prognosis of HPS and the development of acute-on-chronic liver failure (ACLF), and related factors.

Methods

A total of 142 patients with cirrhosis who underwent saline-agitated contrast echocardiography for the diagnosis of HPS were enrolled and observed prospectively from 2014 to 2019.

Results

A total of 59 patients (41%) were diagnosed with HPS (24 grade 1, 23 grade 2, 12 grade 3). Thirty-eight and 37 patients died in the HPS and non-HPS groups, respectively (p < 0.01). The 5-year survival rate was 47% in the HPS group and 62% in the non-HPS group. In the Cox proportional hazards model, HPS and Model for End-stage Liver Disease (MELD) score ≥ 18, and Child–Turcotte–Pugh (CTP) class B/C were significant risk factors for mortality after adjusting for other risk factors (HPS hazard ratio [HR] = 1.9, p = 0.01; MELD score ≥ 18 HR = 2.3, p < 0.01; CTP class B/C HR = 2.9, p < 0.01). Compared to that in non-HPS group, the HPS group had a significantly higher incidence of ACLF during follow-up (p < 0.01) and more frequently presented with lung involvement of ACLF (p = 0.03).

Conclusions

In the long-term follow-up cohort, patients with HPS showed poorer prognosis than that of patients without HPS. HPS was a risk factor for ACLF development independent of hepatic dysfunction, and lung involvement was significantly common than without ACLF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Data will be available according to request.

Abbreviations

HPS:

Hepatopulmonary syndrome

ACLF:

Acute-on-chronic liver failure

LT:

Liver transplantation

CPT:

Child–Turcotte–Pugh

MELD:

Model for end-stage liver disease

INR:

International normalized ratio

HR:

Hazard ratio

CI:

Confidence interval

SBP:

Spontaneous bacterial peritonitis

HBV:

Hepatitis B virus infection

HCV:

Hepatitis C virus infection

Cr:

Creatinine

Hb:

Hemoglobin

Plt:

Platelet

Alb:

Albumin

HRS:

Hepatorenal syndrome

HCC:

Hepatocellular carcinoma

References

  1. 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;24:1285–98.

    Article  CAS  Google Scholar 

  2. Al-Harbi A, Abdullah K, Al-Abdulkareem A, Alghamdi A, Al-Jahdali H. Prevalence, severity, and prognostic effect of hepatopulmonary syndrome in liver transplant candidates. Ann Transplant. 2016;21:180–4.

    Article  CAS  Google Scholar 

  3. Enache I, Oswald-Mammosser M, Woehl-Jaegle ML, et al. Cirrhotic cardiomyopathy and hepatopulmonary syndrome: prevalence and prognosis in a series of patients. Respir Med. 2013;107:1030–6.

    Article  Google Scholar 

  4. Rodriguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome–a liver-induced lung vascular disorder. N Engl J Med. 2008;358:2378–87.

    Article  CAS  Google Scholar 

  5. Kim MY, Baik SK, Lee SS. Hemodynamic alterations in cirrhosis and portal hypertension. Korean J Hepatol. 2010;16:347–52.

    Article  Google Scholar 

  6. Rodriguez-Roisin R, Krowka MJ, Herve P, Fallon MB, Committee ERSTFP-HVDS. Pulmonary-hepatic vascular disorders (PHD). Eur Respir J 2004;24:861–880.

  7. Baik SK, Fouad TR, Lee SS. Cirrhotic cardiomyopathy. Orphanet J Rare Dis. 2007;2:15.

    Article  Google Scholar 

  8. Stoller JK, Lange PA, Westveer MK, Carey WD, Vogt D, Henderson JM. Prevalence and reversibility of the hepatopulmonary syndrome after liver transplantation. The Cleveland Clinic experience. West J Med 1995;163:133–138.

  9. 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;118:615–24.

    Article  CAS  Google Scholar 

  10. Swanson KL, Wiesner RH, Krowka MJ. Natural history of hepatopulmonary syndrome: Impact of liver transplantation. Hepatology. 2005;41:1122–9.

    Article  Google Scholar 

  11. Bottari G, Mazzeo AT, Santamaria LB. The importance of predicting the prognosis in patients with hepatopulmonary syndrome: a simple scoring system. Transplant Proc. 2006;38:795–7.

    Article  CAS  Google Scholar 

  12. Mokhtarifar A, Azimi H, Esmaeelzadeh A, Ebrahimi M, Eghbali SA. Frequency of hepatopulmonary syndrome (HPS) among patients with liver cirrhosis: a letter to editor. Hepat Mon 2016;16:e35990.

  13. Warner S, McKiernan PJ, Hartley J, et al. Hepatopulmonary syndrome in children: a 20-year review of presenting symptoms, clinical progression, and transplant outcome. Liver Transpl. 2018;24:1271–9.

    Article  Google Scholar 

  14. Yi HM, Cai CJ, Lu MQ, et al. [Risk factors predicting the prognosis of orthotopic liver transplantation in hepatopulmonary syndrome]. Zhonghua Wai Ke Za Zhi 2009;47:1312–1315.

  15. Park SH, Plank LD, Suk KT, et al. Trends in the prevalence of chronic liver disease in the Korean adult population, 1998–2017. Clin Mol Hepatol. 2020;26:209–15.

    Article  Google Scholar 

  16. Suk KT, Kim MY, Jeong SW, Jang JY, Jang YO, Baik SK. Impact of bacterial translocation on hepatopulmonary syndrome: a prospective observational study. Dig Dis Sci. 2018;63:248–56.

    Article  CAS  Google Scholar 

  17. Park TJ, Ahn KS, Kim YH, et al. Improved severe hepatopulmonary syndrome after liver transplantation in an adolescent with end-stage liver disease secondary to biliary atresia. Clin Mol Hepatol. 2014;20:76–80.

    Article  Google Scholar 

  18. Laurie SS, Yang X, Elliott JE, Beasley KM, Lovering AT. Hypoxia-induced intrapulmonary arteriovenous shunting at rest in healthy humans. J Appl Physiol. 1985;2010(109):1072–9.

    Google Scholar 

  19. Stickland MK, Lovering AT. Exercise-induced intrapulmonary arteriovenous shunting and pulmonary gas exchange. Exerc Sport Sci Rev. 2006;34:99–106.

    Article  Google Scholar 

  20. Suk KT. Hepatic venous pressure gradient: clinical use in chronic liver disease. Clin Mol Hepatol. 2014;20:6–14.

    Article  Google Scholar 

  21. Krowka MJ, Fallon MB, Kawut SM, et al. International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation. 2016;100:1440–52.

    Article  Google Scholar 

  22. 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;11:567–72.

    Article  CAS  Google Scholar 

  23. Zhang HY, Han DW, Zhao ZF, et al. Multiple pathogenic factor-induced complications of cirrhosis in rats: a new model of hepatopulmonary syndrome with intestinal endotoxemia. World J Gastroenterol. 2007;13:3500–7.

    Article  CAS  Google Scholar 

  24. Kim G, Kim J, Lim YL, Kim MY, Baik SK. Renin-angiotensin system inhibitors and fibrosis in chronic liver disease: a systematic review. Hepatol Int. 2016;10:819–28.

    Article  CAS  Google Scholar 

  25. Lopez-Sanchez GN, Dominguez-Perez M, Uribe M, Nuno-Lambarri N. The fibrogenic process and the unleashing of acute-on-chronic liver failure. Clin Mol Hepatol. 2020;26:7–15.

    Article  Google Scholar 

  26. Schenk P, Schoniger-Hekele M, Fuhrmann V, Madl C, Silberhumer G, Muller C. Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis. Gastroenterology. 2003;125:1042–52.

    Article  Google Scholar 

  27. Chang Y, Suk KT, Jeong SW, et al. Application of hepatic venous pressure gradient to predict prognosis in cirrhotic patients with a low Model for End-stage Liver Disease score. Diagnostics (Basel) 2020;10(10).

  28. Arteel GE. Liver-lung axes in alcohol-related liver disease. Clin Mol Hepatol. 2020;26:670–6.

    Article  Google Scholar 

  29. Grilo I, Pascasio JM, Tirado JL, et al. The utility of the macro-aggregated albumin lung perfusion scan in the diagnosis and prognosis of hepatopulmonary syndrome in cirrhotic patients candidates for liver transplantation. Rev Esp Enferm Dig. 2017;109:335–43.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the assistance of the Regeneration Medicine Research Center and Mitohormesis Research Center of Yonsei University Wonju College of Medicine, as well as the study participants.

Funding

This study was supported by the Research Supporting Program of The Korean Association for the Study of the Liver and the Korean Liver Foundation (KASLKLF2017-04).

Author information

Author notes

  1. Han Seul Ki and MoonYoung Kim These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20, Ilsanro, Wonju, 26426, Republic of Korea

    Seul Ki Han, Moon Young Kim, Seong Hee Kang & Soon Koo Baik

  2. Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea

    Moon Young Kim, Seong Hee Kang & Soon Koo Baik

  3. Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea

    Moon Young Kim & Soon Koo Baik

  4. Department of Internal Medicine, Hanllym University College of Medicine, Chuncheon, South Korea

    Ki Tae Suk

Authors
  1. Seul Ki Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moon Young Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seong Hee Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ki Tae Suk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Soon Koo Baik
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design, material preparation, data collection and analysis were performed by Seul Ki Han, Moon Young Kim. The first draft of the manuscript was written by Seul Ki Han and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Soon Koo Baik.

Ethics declarations

Conflict of interests

None.

Patient consent statement

Written informed consent for participation in the study was obtained from all patients.

Ethics approval statement

This study was approved by the Institutional Review Board for Human Research at Yonsei University Wonju Severance Christian Hospital (CR 314038).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 123 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Han, S.K., Kim, M.Y., Kang, S.H. et al. Hepatopulmonary syndrome is related to the development of acute-on-chronic liver failure and poor prognosis in cirrhotic patients. Hepatol Int 15, 1207–1214 (2021). https://doi.org/10.1007/s12072-021-10226-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-021-10226-2

Keywords

Search

Navigation