Risk factors for portopulmonary hypertension in liver cirrhosis and construction of a predictive model

Jing KUANG; Shuangqin TENG; Tongtong SHEN; Yiran YAN; Wei WANG; Chuan SHEN; Caiyan ZHAO

doi:10.12449/JCH240914

Volume 40 Issue 9

Sep. 2024

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Article Navigation > Journal of Clinical Hepatology > 2024 > 40(9): 1802-1806

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Risk factors for portopulmonary hypertension in liver cirrhosis and construction of a predictive model

DOI: 10.12449/JCH240914

Department of Infectious Diseases and Hepatology，The Third Affiliated Hospital of Hebei Medical University，Shijiazhuang 050051，China

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Corresponding author: WANG Wei， wangwei_1211@126.com （ORCID： 0000-0002-3737-1492）
Received Date: 2023-12-31
Accepted Date: 2024-02-01
Published Date: 2024-09-25

Abstract

Abstract

Objective To investigate the risk factors for portopulmonary hypertension （POPH） in liver cirrhosis， and to construct a noninvasive predictive model. Methods A retrospective analysis was performed for the clinical data of 310 cirrhotic patients with portal hypertension who were hospitalized in The Third Affiliated Hospital of Hebei Medical University from January 2013 to August 2022， and according to whether pulmonary artery systolic pressure was ≥40 mmHg on ultrasound， the patients were divided into POPH group with 31 patients and non-POPH group with 279 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to determine the independent risk factors for POPH， and a nomogram prediction model was constructed. The Bootstrap resampling method was used for internal validation， and C-index and calibration curve were used to assess the discriminatory ability and consistency of the model. The rms package was used to plot the nomogram. Results Compared with the non-POPH group， the POPH group had a significantly younger age， a significantly higher proportion of women or patients with hepatic encephalopathy or Child-Pugh class C disease， and significantly higher levels of direct bilirubin， Model for End-Stage Liver Disease score， albumin-bilirubin （ALBI） score， international normalized ratio， prothrombin time， FIB-4 index， LOK score， and Forns index， as well as significantly lower levels of serum albumin， alanine aminotransferase， gamma-glutamyl transpeptidase， hemoglobin， total cholesterol， and triglycerides （all P<0.05）. The multivariate analysis showed that sex （odds ratio ［OR］=0.172， 95% confidence interval ［CI］： 0.064‍ ‍—‍ ‍0.462， P<0.001）， age （OR=0.944， 95%CI：0.901‍ ‍—‍ ‍0.989， P=0.016）， ALBI score （OR=3.091， 95%CI： 1.100‍ ‍—‍ ‍8.687， P=0.032）， and hepatic encephalopathy （OR=3.466， 95%CI： 1.331‍ ‍—‍ ‍9.031， P=0.011） were independent risk factors for POPH. A predictive model for POPH in liver cirrhosis was established based on the above independent risk factors， with a C-index of 0.796 （95%CI： 0.701‍ ‍—‍ ‍0.890）， suggesting that the model had good discriminatory ability， and the calibration curve showed that the model had good calibration ability， suggesting that the model had certain predictive efficacy. Conclusion Young female individuals， elevated ALBI score， and comorbidity with hepatic encephalopathy are independent risk factors for POPH in patients with liver cirrhosis， and the predictive model established based on these factors has a certain clinical application value.
- Liver Cirrhosis,
- Hypertension， Portal,
- Pulmonary Arterial Hypertension,
- Risk Factors,
- Nomograms

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References

[1]	KHADERI S, KHAN R, SAFDAR Z, et al. Long-term follow-up of portopulmonary hypertension patients after liver transplantation[J]. Liver Transpl, 2014, 20( 6): 724- 727. DOI: 10.1002/lt.23870.
[2]	GBD Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet Gastroenterol Hepatol, 2020, 5( 3): 245- 266. DOI: 10.1016/S2468-1253(19)30349-8.
[3]	JOSE A, SHAH SA, ANWAR N, et al. Pulmonary vascular resistance predicts mortality and graft failure in transplantation patients with portopulmonary hypertension[J]. Liver Transpl, 2021, 27( 12): 1811- 1823. DOI: 10.1002/lt.26091.
[4]	Chinese Society of Hepatology, Chinese Medical Association. Chinese guidelines on the management of liver cirrhosis[J]. J Clin Hepatol, 2019, 35( 11): 2408- 2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006. 中华医学会肝病学分会. 肝硬化诊治指南[J]. 临床肝胆病杂志, 2019, 35( 11): 2408- 2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.
[5]	MCLAUGHLIN VV, ARCHER SL, BADESCH DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association[J]. J Am Coll Cardiol, 2009, 53( 17): 1573- 1619. DOI: 10.1016/j.jacc.2009.01.004.
[6]	TU Y, LI X, CHEN MJ, et al. Value of platelet count and related scoring models in predicting the prognosis of hepatitis B virus-related acute-on-chronic liver failure[J]. J Clin Hepatol, 2023, 39( 6): 1308- 1312. DOI: 10.3969/j.issn.1001-5256.2023.06.009. 涂颖, 李雪, 陈美娟, 等. 血小板计数及相关评分模型对HBV相关慢加急性肝衰竭预后的预测价值[J]. 临床肝胆病杂志, 2023, 39( 6): 1308- 1312. DOI: 10.3969/j.issn.1001-5256.2023.06.009.
[7]	WANG L, FENG YM, MA XW, et al. Diagnostic efficacy of noninvasive liver fibrosis indexes in predicting portal hypertension in patients with cirrhosis[J]. PLoS One, 2017, 12( 8): e0182969. DOI: 10.1371/journal.pone.0182969.
[8]	MA LJ, HE C. The relationship between APRI and S index and Child Pugh in patients with hepatitis B cirrhosis[J]. Chin Hepatol, 2019, 24( 4): 448- 449. DOI: 10.3969/j.issn.1008-1704.2019.04.032. 马丽君, 何聪. APRI及S指数与乙型肝炎肝硬化Child-Pugh肝功能分级的关系[J]. 肝脏, 2019, 24( 4): 448- 449. DOI: 10.3969/j.issn.1008-1704.2019.04.032.
[9]	KAWUT SM, KROWKA MJ, TROTTER JF, et al. Clinical risk factors for portopulmonary hypertension[J]. Hepatology, 2008, 48( 1): 196- 203. DOI: 10.1002/hep.22275.
[10]	CASTAÑO G, SOOKOIAN S. Female sex and autoimmune hepatitis and the risk of portopulmonary hypertension[J]. Hepatology, 2008, 48( 6): 2090. DOI: 10.1002/hep.22599.
[11]	DUBROCK HM, CARTIN-CEBA R, CHANNICK RN, et al. Sex differences in portopulmonary hypertension[J]. Chest, 2021, 159( 1): 328- 336. DOI: 10.1016/j.chest.2020.07.081.
[12]	ROBERTS KE, FALLON MB, KROWKA MJ, et al. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease[J]. Am J Respir Crit Care Med, 2009, 179( 9): 835- 842. DOI: 10.1164/rccm.200809-1472OC.
[13]	AL-NAAMANI N, KROWKA MJ, FORDE KA, et al. Estrogen signaling and portopulmonary hypertension: The pulmonary vascular complications of liver disease study(PVCLD2)[J]. Hepatology, 2021, 73( 2): 726- 737. DOI: 10.1002/hep.31314.
[14]	SHAO YM, YIN X, QIN TT, et al. Prevalence and associated factors of portopulmonary hypertension in patients with portal hypertension: A case-control study[J]. Biomed Res Int, 2021, 2021: 5595614. DOI: 10.1155/2021/5595614.
[15]	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[J]. Hepatol Res, 2021, 51( 12): 1207- 1218. DOI: 10.1111/hepr.13714.
[16]	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]. J Clin Oncol, 2015, 33( 6): 550- 558. DOI: 10.1200/JCO.2014.57.9151.
[17]	FUJITA K, OURA K, YONEYAMA H, et al. Albumin-bilirubin score indicates liver fibrosis staging and prognosis in patients with chronic hepatitis C[J]. Hepatol Res, 2019, 49( 7): 731- 742. DOI: 10.1111/hepr.13333.
[18]	YAMASHITA Y, UMEMURA T, KIMURA T, et al. Prognostic utility of albumin-bilirubin grade in Japanese patients with primary biliary cholangitis[J]. JHEP Rep, 2022, 5( 4): 100662. DOI: 10.1016/j.jhepr.2022.100662.
[19]	WANG J, ZHANG ZP, YAN XM, et al. Albumin-Bilirubin(ALBI) as an accurate and simple prognostic score for chronic hepatitis B-related liver cirrhosis[J]. Dig Liver Dis, 2019, 51( 8): 1172- 1178. DOI: 10.1016/j.dld.2019.01.011.
[20]	WANG YY, ZHONG JH, SU ZY, et al. Albumin-bilirubin versus Child-Pugh score as a predictor of outcome after liver resection for hepatocellular carcinoma[J]. Br J Surg, 2016, 103( 6): 725- 734. DOI: 10.1002/bjs.10095.
[21]	BAJAJ JS, RIDLON JM, HYLEMON PB, et al. Linkage of gut microbiome with cognition in hepatic encephalopathy[J]. Am J Physiol Gastrointest Liver Physiol, 2012, 302( 1): G168- G175. DOI: 10.1152/ajpgi.00190.2011.
[22]	JAIN L, SHARMA BC, SHARMA P, et al. Serum endotoxin and inflammatory mediators in patients with cirrhosis and hepatic encephalopathy[J]. Dig Liver Dis, 2012, 44( 12): 1027- 1031. DOI: 10.1016/j.dld.2012.07.002.
[23]	CHEN YH, YUAN W, MENG LK, et al. The role and mechanism of gut microbiota in pulmonary arterial hypertension[J]. Nutrients, 2022, 14( 20): 4278. DOI: 10.3390/nu14204278.
[24]	ISHIDA K, NAMISAKI T, MURATA K, et al. Accuracy of fibrosis-4 index in identification of patients with cirrhosis who could potentially avoid variceal screening endoscopy[J]. J Clin Med, 2020, 9( 11): 3510. DOI: 10.3390/jcm9113510.

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