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

Hepatology International - Tập 17 - Trang 139-149 - 2022
Masanori Atsukawa1, Akihito Tsubota2, Chisa Kondo1, Kaori-Shioda Koyano1, Toru Ishikawa3, Hidenori Toyoda4, Koichi Takaguchi5, Tsunamasa Watanabe6, Kentaro Matsuura7, Chikara Ogawa8, Atsushi Hiraoka9, Hironao Okubo10, Masakuni Tateyama11, Haruki Uojima12, Akito Nozaki13, Makoto Chuma13, Keizo Kato14, Shigeru Mikami15, Joji Tani16, Asahiro Morishita16, Kazuhito Kawata17, Toshifumi Tada18, Yoshihiro Furuichi19, Tomomi Okubo20, Tadamichi Kawano1, Taeang Arai1, Naoto Kawabe21, Naohiro Kawamura22, Tadashi Ikegami23, Makoto Nakamuta24, Ryuta Shigefuku25, Motoh Iwasa25, Yasuhito Tanaka11, Masaru Hatano26, Katsuhiko Iwakiri1
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, SendagiTokyo, Japan
2Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan
3Department of Hepatology, Saiseikai Niigata Hospital, Niigata, Japan
4Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
5Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
6Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
7Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan
8Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
9Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
10Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan
11Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
12Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan
13Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
14Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatusdo Central General Hospital, Matsudo, Japan
15Division of Gastroenterology, Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan.
16Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
17Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
18Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Hygo, Japan
19Department of Clinical Laboratory and Endoscopy, Tokyo Women’s Medical University Adachi Medical Center, Tokyo, Japan
20Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
21Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Aichi, Japan
22Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
23Division of Hepatology and Gastroenterology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
24National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
25Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
26Department of Advanced Medical Center for Heart Failure, The University of Tokyo Hospital, Tokyo, Japan

Tóm tắt

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. 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. 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.

Tài liệu tham khảo

Salerno F, Gerbes A, Ginès P, et al. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56(9):1310–1318 Hervé P, Lebrec D, Brenot F, et al. Pulmonary vascular disorders in portal hypertension. Eur Respir J. 1998;11(5):1153–1166 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 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 Savale L, Watherald J, Sitbon O. Portopulmonary hypertension. Semin Respir Crit Care Med. 2017;38(5):651–661 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 Kawut SM, Taichman DB, Ahya VN, et al. Hemodynamics and survival of patients with portopulmonary hypertension. Liver Transpl. 2005;11(9):1107–1111 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 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 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 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 Krowka MJ, Swanson KL, Frantz RP, et al. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology. 2006;44(6):1502–1510 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 Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913 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 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 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 Krowka MJ, Miller DP, Barst RJ, et al. Portopulmonary hypertension: a report from the US-based REVEAL registry. Chest. 2012;141(4):906–915 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 Frost A, Badesch D, Gibbs JSR, et al. Diagnosis of pulmonary hypertension. Eur Respir J. 2019;53(1):1801904 Kuo PC, Plotkin JS, Johnson LB, et al. Distinctive clinical features of portopulmonary hypertension. Chest. 1997;112(4):980–986 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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
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Hepatology International

Tập 17

139-149

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