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Open Access 25-04-2024 | Liver Cirrhosis | Original Article

Predicting response to non-selective beta-blockers with liver–spleen stiffness and heart rate in patients with liver cirrhosis and high-risk varices

Authors: Mauro Giuffrè, Johannes Dupont, Alessia Visintin, Flora Masutti, Fabio Monica, Kisung You, Dennis L. Shung, Lory Saveria Crocè, The NSBB-Elasto-Response-Prediction Group

Published in: Hepatology International

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Abstract

Introduction

Non-selective beta-blockers (NSBB) are used for primary prophylaxis in patients with liver cirrhosis and high-risk varices (HRVs). Assessing therapeutic response is challenging due to the invasive nature of hepatic venous pressure gradient (HVPG) measurement. This study aims to define a noninvasive machine-learning based approach to determine response to NSBB in patients with liver cirrhosis and HRVs.

Methods

We conducted a prospective study on a cohort of cirrhotic patients with documented HRVs receiving NSBB treatment. Patients were followed-up with clinical and elastography appointments at 3, 6, and 12 months after NSBB treatment initiation. NSBB response was defined as stationary or downstaging variceal grading at the 12-month esophagogastroduodenoscopy (EGD). In contrast, non-response was defined as upstaging variceal grading at the 12-month EGD or at least one variceal hemorrhage episode during the 12-month follow-up. We chose cut-off values for univariate and multivariate model with 100% specificity.

Results

According to least absolute shrinkage and selection operator (LASSO) regression, spleen stiffness (SS) and liver stiffness (LS) percentual decrease, along with changes in heart rate (HR) at 3 months were the most significant predictors of NSBB response. A decrease > 11.5% in SS, > 16.8% in LS, and > 25.3% in HR was associated with better prediction of clinical response to NSBB. SS percentual decrease showed the highest accuracy (86.4%) with high sensitivity (78.8%) when compared to LS and HR. The multivariate model incorporating SS, LS, and HR showed the highest discrimination and calibration metrics (AUROC = 0.96), with the optimal cut-off of 0.90 (sensitivity 94.2%, specificity 100%, PPV 95.7%, NPV 100%, accuracy 97.5%).
Literature
1.
go back to reference Garcia-Tsao G, Abraldes JG, Berzigotti A. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017;65:310–335.CrossRefPubMed Garcia-Tsao G, Abraldes JG, Berzigotti A. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017;65:310–335.CrossRefPubMed
3.
go back to reference Berzigotti A. Non-invasive evaluation of portal hypertension using ultrasound elastography. J Hepatol. 2017;67:399–411.CrossRefPubMed Berzigotti A. Non-invasive evaluation of portal hypertension using ultrasound elastography. J Hepatol. 2017;67:399–411.CrossRefPubMed
4.
go back to reference Ravaioli F, Montagnani M, Lisotti A. Noninvasive assessment of portal hypertension in advanced chronic liver disease: an update. Gastroenterol Res Pract. 2018;2018:1–11.CrossRef Ravaioli F, Montagnani M, Lisotti A. Noninvasive assessment of portal hypertension in advanced chronic liver disease: an update. Gastroenterol Res Pract. 2018;2018:1–11.CrossRef
5.
7.
go back to reference Hu X, Huang X, Hou J. Diagnostic accuracy of spleen stiffness to evaluate portal hypertension and esophageal varices in chronic liver disease: a systematic review and meta-analysis. Eur Radiol. 2021;31:2392–2404.CrossRefPubMed Hu X, Huang X, Hou J. Diagnostic accuracy of spleen stiffness to evaluate portal hypertension and esophageal varices in chronic liver disease: a systematic review and meta-analysis. Eur Radiol. 2021;31:2392–2404.CrossRefPubMed
9.
go back to reference Franchis de R, Bosch J, Garcia-Tsao G. Baveno VII—renewing consensus in portal hypertension. J Hepatol. 2022;76:959–974.CrossRefPubMed Franchis de R, Bosch J, Garcia-Tsao G. Baveno VII—renewing consensus in portal hypertension. J Hepatol. 2022;76:959–974.CrossRefPubMed
10.
go back to reference Rodrigues SG, Mendoza YP, Bosch J. Beta-blockers in cirrhosis: evidence-based indications and limitations. JHEP Rep. 2020;2:100063.CrossRefPubMed Rodrigues SG, Mendoza YP, Bosch J. Beta-blockers in cirrhosis: evidence-based indications and limitations. JHEP Rep. 2020;2:100063.CrossRefPubMed
11.
go back to reference Choi S-Y , Jeong WK, Kim Y. Shear-wave elastography: a noninvasive tool for monitoring changing hepatic venous pressure gradients in patients with cirrhosis. Radiology. 2014;273:917–926.CrossRefPubMed Choi S-Y , Jeong WK, Kim Y. Shear-wave elastography: a noninvasive tool for monitoring changing hepatic venous pressure gradients in patients with cirrhosis. Radiology. 2014;273:917–926.CrossRefPubMed
12.
go back to reference Binzberger A, Hänle M, Pfahler M. Spleen and liver stiffness evaluation by ARFI imaging: a reliable tool for a short-term monitoring of portal hypertension? Int J Hepatol. 2022;2022:1–14.CrossRef Binzberger A, Hänle M, Pfahler M. Spleen and liver stiffness evaluation by ARFI imaging: a reliable tool for a short-term monitoring of portal hypertension? Int J Hepatol. 2022;2022:1–14.CrossRef
13.
go back to reference Marasco G, Dajti E, Ravaioli F. Spleen stiffness measurement for assessing the response to β-blockers therapy for high-risk esophageal varices patients. Hepatol Int. 2020;14:850–857.CrossRefPubMed Marasco G, Dajti E, Ravaioli F. Spleen stiffness measurement for assessing the response to β-blockers therapy for high-risk esophageal varices patients. Hepatol Int. 2020;14:850–857.CrossRefPubMed
14.
go back to reference Kim HY, So YH , Kim W. Non-invasive response prediction in prophylactic carvedilol therapy for cirrhotic patients with esophageal varices. J Hepatol. 2019;70:412–422.CrossRefPubMed Kim HY, So YH , Kim W. Non-invasive response prediction in prophylactic carvedilol therapy for cirrhotic patients with esophageal varices. J Hepatol. 2019;70:412–422.CrossRefPubMed
15.
go back to reference Aubé C, Bazeries P, Lebigot J. Liver fibrosis, cirrhosis, and cirrhosis-related nodules: Imaging diagnosis and surveillance. Diagn Interv Imaging. 2017;98:455–468.CrossRefPubMed Aubé C, Bazeries P, Lebigot J. Liver fibrosis, cirrhosis, and cirrhosis-related nodules: Imaging diagnosis and surveillance. Diagn Interv Imaging. 2017;98:455–468.CrossRefPubMed
16.
go back to reference Ferraioli G, Roccarina D. Update on the role of elastography in liver disease. Therap Adv Gastroenterol. 2022;15:175628482211406.CrossRef Ferraioli G, Roccarina D. Update on the role of elastography in liver disease. Therap Adv Gastroenterol. 2022;15:175628482211406.CrossRef
17.
go back to reference Pugh RNH , Murray-Lyon IM, Dawson JL. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 2005;60:646–649.CrossRef Pugh RNH , Murray-Lyon IM, Dawson JL. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 2005;60:646–649.CrossRef
18.
19.
go back to reference De Franchis R, Abraldes JG, Bajaj J, et al. Expanding consensus in portal hypertension Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;743–752. De Franchis R, Abraldes JG, Bajaj J, et al. Expanding consensus in portal hypertension Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;743–752.
20.
go back to reference Abby C, Philips Sahney A. Oesophageal and gastric varices: historical aspects, classification and grading: everything in one place. Gastroenterol Rep (Oxf). 2016;4:186–195.CrossRefPubMed Abby C, Philips Sahney A. Oesophageal and gastric varices: historical aspects, classification and grading: everything in one place. Gastroenterol Rep (Oxf). 2016;4:186–195.CrossRefPubMed
21.
go back to reference Giuffrè M, Macor D, Masutti F. Evaluation of spleen stiffness in healthy volunteers using point shear wave elastography. Ann Hepatol. 2019 ;18:736–741.CrossRefPubMed Giuffrè M, Macor D, Masutti F. Evaluation of spleen stiffness in healthy volunteers using point shear wave elastography. Ann Hepatol. 2019 ;18:736–741.CrossRefPubMed
22.
go back to reference Giuffrè M, Macor D, Masutti F. Spleen Stiffness Probability Index (SSPI): a simple and accurate method to detect esophageal varices in patients with compensated liver cirrhosis. Ann Hepatol. 2020;19:53–61.CrossRefPubMed Giuffrè M, Macor D, Masutti F. Spleen Stiffness Probability Index (SSPI): a simple and accurate method to detect esophageal varices in patients with compensated liver cirrhosis. Ann Hepatol. 2020;19:53–61.CrossRefPubMed
23.
go back to reference Giuffrè M, Fouraki S, Comar M. The Importance of transaminases flare in liver elastography: characterization of the probability of liver fibrosis overestimation by hepatitis C virus-induced cytolysis. Microorganisms. 2020;8:348.CrossRefPubMedPubMedCentral Giuffrè M, Fouraki S, Comar M. The Importance of transaminases flare in liver elastography: characterization of the probability of liver fibrosis overestimation by hepatitis C virus-induced cytolysis. Microorganisms. 2020;8:348.CrossRefPubMedPubMedCentral
24.
go back to reference Giuffrè M, Giuricin M, Bonazza D. Optimization of point-shear wave elastography by skin-to-liver distance to assess liver fibrosis in patients undergoing bariatric surgery. Diagnostics. 2020;10:795.CrossRefPubMedPubMedCentral Giuffrè M, Giuricin M, Bonazza D. Optimization of point-shear wave elastography by skin-to-liver distance to assess liver fibrosis in patients undergoing bariatric surgery. Diagnostics. 2020;10:795.CrossRefPubMedPubMedCentral
25.
go back to reference Giuffrè M, Bedogni G, Abazia C. Spleen stiffness can be employed to assess the efficacy of spontaneous portosystemic shunts in relieving portal hypertension. Ann Hepatol. 2020;19:691–693.CrossRefPubMed Giuffrè M, Bedogni G, Abazia C. Spleen stiffness can be employed to assess the efficacy of spontaneous portosystemic shunts in relieving portal hypertension. Ann Hepatol. 2020;19:691–693.CrossRefPubMed
26.
go back to reference Giuffrè M, Fouraki S, Campigotto M. Alanine aminotransferase and spleno-portal dynamics affect spleen stiffness measured by point shear-wave elastography in patients with chronic hepatitis C in the absence of significant liver fibrosis. J Ultrasound. 2021;24:67–73.CrossRefPubMed Giuffrè M, Fouraki S, Campigotto M. Alanine aminotransferase and spleno-portal dynamics affect spleen stiffness measured by point shear-wave elastography in patients with chronic hepatitis C in the absence of significant liver fibrosis. J Ultrasound. 2021;24:67–73.CrossRefPubMed
27.
go back to reference Barr RG , Wilson SR, Rubens D. Update to the Society of radiologists in ultrasound liver elastography consensus statement. Radiology. 2020;296:263–274.CrossRefPubMed Barr RG , Wilson SR, Rubens D. Update to the Society of radiologists in ultrasound liver elastography consensus statement. Radiology. 2020;296:263–274.CrossRefPubMed
28.
go back to reference Shapiro SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrika. 1965;52:591–611.CrossRef Shapiro SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrika. 1965;52:591–611.CrossRef
29.
30.
go back to reference Tibshirani R. Regression shrinkage and selection via the lasso. J Roy Stat Soc: Ser B (Methodol). 1996;58:267–288.CrossRef Tibshirani R. Regression shrinkage and selection via the lasso. J Roy Stat Soc: Ser B (Methodol). 1996;58:267–288.CrossRef
31.
go back to reference Reiberger T, Ferlitsch A, Payer BA. Non-selective β-blockers improve the correlation of liver stiffness and portal pressure in advanced cirrhosis. J Gastroenterol. 2012;47:561–568.CrossRefPubMed Reiberger T, Ferlitsch A, Payer BA. Non-selective β-blockers improve the correlation of liver stiffness and portal pressure in advanced cirrhosis. J Gastroenterol. 2012;47:561–568.CrossRefPubMed
Metadata
Title
Predicting response to non-selective beta-blockers with liver–spleen stiffness and heart rate in patients with liver cirrhosis and high-risk varices
Authors
Mauro Giuffrè
Johannes Dupont
Alessia Visintin
Flora Masutti
Fabio Monica
Kisung You
Dennis L. Shung
Lory Saveria Crocè
The NSBB-Elasto-Response-Prediction Group
Publication date
25-04-2024
Publisher
Springer India
Published in
Hepatology International
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-024-10649-7
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