Skip to main content

Advertisement

SpringerLink
Log in

Risk factors for portopulmonary hypertension in patients with cirrhosis: a prospective, multicenter study

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

Abstract

Background

Tricuspid regurgitation pressure gradient (TRPG) measurement by echocardiography is recommended as the most objective examination to detect portopulmonary hypertension (PoPH). This study aimed to identify factors associated with a high TRPG in patients with cirrhosis and develop a scoring model for identifying patients who are most likely to benefit from echocardiography investigations.

Results

A total of 486 patients who underwent echocardiography were randomly allocated to the derivation and validation sets at a ratio of 2:1. Of the patients, 51 (10.5%) had TRPG ≥ 35 mmHg. The median brain natriuretic peptide (BNP) was 39.5 pg/mL. Shortness of breath (SOB) was reported by 91 (18.7%) patients. In the derivation set, multivariate analysis identified female gender, shortness of breath, and BNP ≥ 48.9 pg/mL as independent factors for TRPG ≥ 35 mmHg. The risk score for predicting TRPG ≥ 35 mmHg was calculated as follows: − 3.596 + 1.250 × gender (female: 1, male: 0) + 1.093 × SOB (presence: 1, absence: 0) + 0.953 × BNP (≥ 48.9 pg/mL: 1, < 48.9 pg/mL: 0). The risk score yielded sensitivity of 66.7%, specificity of 75.3%, positive predictive value of 25.5%, negative predict value of 94.3%, and predictive accuracy of 74.4% for predicting TRPG ≥ 35 mmHg. These results were almost similar in the validation set, indicating the reproducibility and validity of the risk score.

Conclusions

This study clarified the characteristics of patients with suspected PoPH and developed a scoring model for identifying patients at high risk of PoPH, which may be used in selecting patients that may benefit from echocardiography.

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

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Salerno F, Gerbes A, Ginès P, et al. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56(9):1310–1318

    CAS  Google Scholar 

  2. Hervé P, Lebrec D, Brenot F, et al. Pulmonary vascular disorders in portal hypertension. Eur Respir J. 1998;11(5):1153–1166

    Article  Google Scholar 

  3. 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(7):1440–1452

    Article  Google Scholar 

  4. Rodríguez-Roisin R, Krowka MJ, Hervé P, et al. ERS task force pulmonary-hepatic vascular disorders (PHD) scientific committee. Pulmonary-hepatic vascular disorders (PHD). Eur Respir J. 2004;24(5):861–880

    Google Scholar 

  5. Savale L, Watherald J, Sitbon O. Portopulmonary hypertension. Semin Respir Crit Care Med. 2017;38(5):651–661

    Article  Google Scholar 

  6. Atsukawa M, Tsubota A, Hatano M, et al. Prevalence and characteristics of portopulmonary hypertension in cirrhotic patients who underwent both hepatic vein and pulmonary artery catheterization. Hepatol Res. 2020;50(11):1244–1254

    Article  Google Scholar 

  7. Kawut SM, Taichman DB, Ahya VN, et al. Hemodynamics and survival of patients with portopulmonary hypertension. Liver Transpl. 2005;11(9):1107–1111

    Article  Google Scholar 

  8. Hayashi R, Kogiso T, Kikuchi N, et al. Portopulmonary hypertension and the risk of high right ventricular systolic pressure in liver transplant candidates. PLoS ONE. 2022;17(4): e0267125

    Article  CAS  Google Scholar 

  9. Chen HS, Xing SR, Xu WG, et al. Portopulmonary hypertension in cirrhotic patients: prevalence, clinical features and risk factors. Exp Ther Med. 2013;5(3):819–824

    Article  Google Scholar 

  10. Shao Y, Yin X, Qin T, et al. Prevalence and associated factors of portopulmonary hypertension in patients with portal hypertension: a case-control study. Biomed Res Int. 2021;2021:5595614

    Article  Google Scholar 

  11. Kawaguchi T, Honda A, Sugiyama Y, et al. Association between the albumin-bilirubin (ALBI) score and severity of portopulmonary hypertension (PoPH): a data-mining analysis. Hepatol Res. 2021;51(12):1207–1218

    Article  CAS  Google Scholar 

  12. Krowka MJ, Swanson KL, Frantz RP, et al. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology. 2006;44(6):1502–1510

    Article  Google Scholar 

  13. Kawut SM, Krowka MJ, Trotter JF, et al. Pulmonary vascular complications of liver disease study group. Clinical risk factors for portopulmonary hypertension. Hepatology. 2008;48(1):196–203

    Article  Google Scholar 

  14. Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913

    Article  CAS  Google Scholar 

  15. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European respiratory society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67–119

    Article  Google Scholar 

  16. Thomas CA, Anderson RJ, Condon DF, et al. Diagnosis and management of pulmonary hypertension in the modern era: insights from the 6th world symposium. Pulm Ther. 2020;6(1):9–22

    Article  Google Scholar 

  17. Swanson KL, Wiesner RH, Nyberg SL, et al. Survival in portopulmonary hypertension: mayo clinic experience categorized by treatment subgroups. Am J Transplant. 2008;8(11):2445–2453

    Article  CAS  Google Scholar 

  18. Krowka MJ, Miller DP, Barst RJ, et al. Portopulmonary hypertension: a report from the US-based REVEAL registry. Chest. 2012;141(4):906–915

    Article  Google Scholar 

  19. Austin MJ, McDougall NI, Wendon JA, et al. Safety and efficacy of combined use of sildenafil, bosentan, and iloprost before and after liver transplantation in severe portopulmonary hypertension. Liver Transpl. 2008;14(3):287–291

    Article  Google Scholar 

  20. Frost A, Badesch D, Gibbs JSR, et al. Diagnosis of pulmonary hypertension. Eur Respir J. 2019;53(1):1801904

    Article  CAS  Google Scholar 

  21. Kuo PC, Plotkin JS, Johnson LB, et al. Distinctive clinical features of portopulmonary hypertension. Chest. 1997;112(4):980–986

    Article  CAS  Google Scholar 

  22. Robalino BD, Moodie DS. Association between primary pulmonary hypertension and portal hypertension: analysis of its pathophysiology and clinical, laboratory and hemodynamic manifestations. J Am Coll Cardiol. 1991;17(2):492–498

    Article  CAS  Google Scholar 

  23. Yoshimaru K, Matsuura T, Takahashi Y, et al. The efficacy of serum brain natriuretic peptide for the early detection of portopulmonary hypertension in biliary atresia patients before liver transplantation. Pediatr Transplant. 2018;22(5): e13203

    Article  Google Scholar 

  24. Ishikawa T, Egusa M, Kawamoto D, et al. Screening for portopulmonary hypertension using computed tomography-based measurements of the main pulmonary artery and ascending aorta diameters in patients with portal hypertension. Hepatol Res. 2022;52(3):255–268

    Article  Google Scholar 

  25. Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33(6):550–558

    Article  Google Scholar 

  26. Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685–713

    Article  Google Scholar 

  27. Sawada N, Kawata T, Daimon M, et al. Detection of pulmonary hypertension with systolic pressure estimated by doppler echocardiography. Int Heart J. 2019;60(4):836–844

    Article  Google Scholar 

  28. Gorrasi J, Pazos A, Florio L, et al. Cardiac output measured by transthoracic echocardiography and Swan-Ganz catheter. A comparative study in mechanically ventilated patients with high positive end-expiratory pressure. Rev Bras Ter Intensiva. 2019;31(4):474–482

    Article  Google Scholar 

  29. Hadengue A, Benhayoun MK, Lebrec D, et al. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology. 1991;100(2):520–528

    Article  CAS  Google Scholar 

  30. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2022;30:2200879

    Google Scholar 

  31. Al-Naamani N, Krowka MJ, Forde KA, et al. Pulmonary vascular complications of liver disease study group. Estrogen signaling and portopulmonary hypertension: the pulmonary vascular complications of liver disease study (PVCLD2). Hepatology. 2021;73(2):726–737

    Article  CAS  Google Scholar 

  32. Roberts KE, Fallon MB, Krowka MJ, et al. Pulmonary vascular complications of liver disease study group. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. Am J Respir Crit Care Med. 2009;179(9):835–842

    Article  Google Scholar 

  33. International PPH Consortium, Lane KB, Machado RD, Pauciulo MW, et al. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet. 2000;26(1):81–84

    Article  Google Scholar 

  34. Deng Z, Morse JH, Slager SL, et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet. 2000;67(3):737–744

    Article  CAS  Google Scholar 

  35. Larkin EK, Newman JH, Austin ED, et al. Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012;186(9):892–896

    Article  Google Scholar 

  36. Austin ED, Cogan JD, West JD, et al. Alterations in oestrogen metabolism: implications for higher penetrance of familial pulmonary arterial hypertension in females. Eur Respir J. 2009;34(5):1093–1099

    Article  CAS  Google Scholar 

  37. Li J, Zhuang Q, Zhang X, Zheng Y, Qiao Z, Zhang J, et al. Prevalence and prognosis of portopulmonary hypertension in 223 liver transplant recipients. Can Respir J. 2018;2018:9629570

    Article  Google Scholar 

Download references

Author information

Author notes

  1. Masanori Atsukawa and Akihito Tsubota have contributed equally to the preparation of this manuscript.

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan

    Masanori Atsukawa, Chisa Kondo, Kaori-Shioda Koyano, Tadamichi Kawano, Taeang Arai & Katsuhiko Iwakiri

  2. Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan

    Akihito Tsubota

  3. Department of Hepatology, Saiseikai Niigata Hospital, Niigata, Japan

    Toru Ishikawa

  4. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan

    Hidenori Toyoda

  5. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan

    Koichi Takaguchi

  6. Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

    Tsunamasa Watanabe

  7. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan

    Kentaro Matsuura

  8. Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan

    Chikara Ogawa

  9. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan

    Atsushi Hiraoka

  10. Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan

    Hironao Okubo

  11. Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Masakuni Tateyama & Yasuhito Tanaka

  12. Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan

    Haruki Uojima

  13. Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan

    Akito Nozaki & Makoto Chuma

  14. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatusdo Central General Hospital, Matsudo, Japan

    Keizo Kato

  15. Division of Gastroenterology, Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan

    Shigeru Mikami

  16. Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan

    Joji Tani & Asahiro Morishita

  17. Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Kazuhito Kawata

  18. Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Hygo, Japan

    Toshifumi Tada

  19. Department of Clinical Laboratory and Endoscopy, Tokyo Women’s Medical University Adachi Medical Center, Tokyo, Japan

    Yoshihiro Furuichi

  20. Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan

    Tomomi Okubo

  21. Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Aichi, Japan

    Naoto Kawabe

  22. Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan

    Naohiro Kawamura

  23. Division of Hepatology and Gastroenterology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan

    Tadashi Ikegami

  24. National Hospital Organization Kyushu Medical Center, Fukuoka, Japan

    Makoto Nakamuta

  25. Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan

    Ryuta Shigefuku & Motoh Iwasa

  26. Department of Advanced Medical Center for Heart Failure, The University of Tokyo Hospital, Tokyo, Japan

    Masaru Hatano

Authors
  1. Masanori Atsukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akihito Tsubota
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chisa Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaori-Shioda Koyano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toru Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hidenori Toyoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Koichi Takaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tsunamasa Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kentaro Matsuura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chikara Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Atsushi Hiraoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hironao Okubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Masakuni Tateyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Haruki Uojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Akito Nozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Makoto Chuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Keizo Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Shigeru Mikami
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Joji Tani
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Asahiro Morishita
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Kazuhito Kawata
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Toshifumi Tada
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Yoshihiro Furuichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Tomomi Okubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Tadamichi Kawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Taeang Arai
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Naoto Kawabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Naohiro Kawamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Tadashi Ikegami
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Makoto Nakamuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Ryuta Shigefuku
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Motoh Iwasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Yasuhito Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  34. Masaru Hatano
    View author publications

    You can also search for this author in PubMed Google Scholar

  35. Katsuhiko Iwakiri
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors provided critical revisions to the study manuscript, and approved the final version submitted for publication. MA, K-SK, TI, HT, KT, TW, KM, CO, AH, HO, MT, HU, AN, MC, KK, SM, JT, AM, KK, YF, TO, TK, TA, NK, NK, TI, MN, RS, MI, YT and MH collected data. MA, TT, MH and KI contributed to the study design. MA and CK analyzed the data. MA and AT contributed to the interpretation of the results and the drafting of the manuscript.

Corresponding author

Correspondence to Masanori Atsukawa.

Ethics declarations

Ethical approval

The present study was conducted following the ethical guidelines established in the 2013 Helsinki Declaration and was approved by the ethics committee of Nippon Medical School (approval no. B-2019-098).

Conflict of interest

The authors declare no conflicts of interest associated with this manuscript.

Additional information

Publisher's Note

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

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Atsukawa, M., Tsubota, A., Kondo, C. et al. Risk factors for portopulmonary hypertension in patients with cirrhosis: a prospective, multicenter study. Hepatol Int 17, 139–149 (2023). https://doi.org/10.1007/s12072-022-10456-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-022-10456-y

Keywords

Search

Navigation