Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis

Michael Praktiknjo; Macarena Simón-Talero; Julia Römer; Davide Roccarina; Javier Martínez; Katharina Lampichler; Anna Baiges; Gavin Low; Elba Llop; Martin H. Maurer; Alexander Zipprich; Michela Triolo; Geert Maleux; Annette Dam Fialla; Claus Dam; Judit Vidal-González; Avik Majumdar; Carmen Picón; Daniel Toth; Anna Darnell; Juan G. Abraldes; Marta López; Christian Jansen; Johannes Chang; Robert Schierwagen; Frank Uschner; Guido Kukuk; Carsten Meyer; Daniel Thomas; Karsten Wolter; Christian P. Strassburg; Wim Laleman; Vincenzo La Mura; Cristina Ripoll; Annalisa Berzigotti; José Luis Calleja; Puneeta Tandon; Virginia Hernandez-Gea; Thomas Reiberger; Agustín Albillos; Emmanuel A. Tsochatzis; Aleksander Krag; Joan Genescà; Jonel Trebicka; Baveno VI (Baveno Cooperation)

doi:10.1016/j.jhep.2019.12.021

Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis

Michael Praktiknjo
, Macarena Simón-Talero
, Julia Römer
, Davide Roccarina
, Javier Martínez
, Katharina Lampichler
, Anna Baiges
, Gavin Low
, Elba Llop
, Martin H. Maurer
, Alexander Zipprich
, Michela Triolo
, Geert Maleux
, Annette Dam Fialla
, Claus Dam
, Judit Vidal-González
, Avik Majumdar
, Carmen Picón
, Daniel Toth
, Anna Darnell

Juan G. Abraldes, Marta López, Christian Jansen, Johannes Chang, Robert Schierwagen, Frank Uschner, Guido Kukuk, Carsten Meyer, Daniel Thomas, Karsten Wolter, Christian P. Strassburg, Wim Laleman, Vincenzo La Mura, Cristina Ripoll, Annalisa Berzigotti, José Luis Calleja, Puneeta Tandon, Virginia Hernandez-Gea, Thomas Reiberger, Agustín Albillos, Emmanuel A. Tsochatzis, Aleksander Krag, Joan Genescà, Jonel Trebicka^*, Baveno VI (Baveno Cooperation)

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.

METHODS: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.

RESULTS: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm 2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02-2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA.

CONCLUSION: This study suggests that TSA >83 mm 2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.

LAY SUMMARY: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.

Originalsprog	Engelsk
Tidsskrift	Journal of Hepatology
Vol/bind	72
Udgave nummer	6
Sider (fra-til)	1140-1150
ISSN	0168-8278
DOI	https://doi.org/10.1016/j.jhep.2019.12.021
Status	Udgivet - jun. 2020

Finansiering

Jonel Trebicka is supported by grants from the Deutsche Forschungsgemeinschaft ( SFB TRR57 , CRC1382 ), Cellex Foundation and European Union's Horizon 2020 research and innovation program GALAXY study (No. 668031), LIVERHOPE (No. 731875 ) and MICROB-PREDICT (No. 825694 ) and the Cellex Foundation . Joan Genescà is a recipient of a Research Intensification grant from Instituto de Salud Carlos III , Spain. The study was partially funded by grants PI15/00066 , and PI18/00947 from Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “Investing in your future”). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivasis supported by Instituto de Salud Carlos III . Macarena Simón-Talero is a recipient of the grant JR 17/00029 from Instituto de Salud Carlos III . MP Sponsored lectures: Gore; AZ Sponsored lectures: Gilead, Abbvie, Norgine, Grifols, Bayer, Gore, BMS; AD Sponsored lectures: Bayer; WL Grants: Boston Scientific , Consultant: Boston Scientific, Abbvie, Gilead, Norgine, Gore; VLM Grants: Gilead Sciences research Scholar Program, Consultant: Gore, Sponsored lectures (National or International): Gore, Abbvie, Alfa-sigma; CR Grant: Schweine Stiftung ; VHG Sponsored lectures (National or International): GORE; TR Grants: Abbvie , Boehringer Ingelheim , Gilead , MSD , Philips Healthcare, Gore ; Consultant: Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; Sponsored lectures (National or International): Abbvie, Gilead, Gore, Intercept, Roche, MSD; AA Grants: Gilead Sciences , Consultant: AbbVie, Gilead Sciences, Gore, Griffols, Intercept Pharmaceuticals, Pfizer and Merck & Co., Sponsored lectures (National or International): AbbVie, Gilead Sciences, Gore, Griffols, Intercept Pharmaceuticals, Pfizer and Merck & Co.; EAT Consultant: Pfizer, Intercept, Gilead, Promethera, Astra Zeneca; JT Grants: Gore , Consultant: Martins Pharma, Ironwood, Gore, Alexion, BMS, Grifols, Sequana Medicals, Versantis, Sponsored lectures (National or International): Gilead, Gore, Alexion, BMS, Grifols, Sequana Medicals, Norgine, Intercept.

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10.1016/j.jhep.2019.12.021Licens: CC BY-NC-ND

Open Access VersionForlagets udgivne version, 488 KBLicens: CC BY-NC-ND

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Citationsformater

Praktiknjo, M., Simón-Talero, M., Römer, J., Roccarina, D., Martínez, J., Lampichler, K., Baiges, A., Low, G., Llop, E., Maurer, M. H., Zipprich, A., Triolo, M., Maleux, G., Fialla, A. D., Dam, C., Vidal-González, J., Majumdar, A., Picón, C., Toth, D., ... Baveno VI (Baveno Cooperation) (2020). Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis. Journal of Hepatology, 72(6), 1140-1150. https://doi.org/10.1016/j.jhep.2019.12.021

@article{127ecd78721e46e8b5314e83ad40f6f6,

title = "Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis",

abstract = "BACKGROUND \& AIMS: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.METHODS: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.RESULTS: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm 2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12\% vs. 21\%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33\% vs. 47\%, p <0.05) and had lower 1-year survival than those with S-TSA (84\% vs. 69\%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95\% CI 1.02-2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77\% vs. 64\%, p <0.001) and more oHE development (35\% vs. 49\%, p <0.001) than those with S-TSA. CONCLUSION: This study suggests that TSA >83 mm 2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. LAY SUMMARY: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.",

keywords = "ACLF, Acute decompensation, Acute-on-chronic liver failure, Ascites, Cirrhosis, Computed tomography, Hepatic encephalopathy, Liver, Portal hypertension, Spontaneous portosystemic shunt, SPSS, TIPS",

author = "Michael Praktiknjo and Macarena Sim{\'o}n-Talero and Julia R{\"o}mer and Davide Roccarina and Javier Mart{\'i}nez and Katharina Lampichler and Anna Baiges and Gavin Low and Elba Llop and Maurer, \{Martin H.\} and Alexander Zipprich and Michela Triolo and Geert Maleux and Fialla, \{Annette Dam\} and Claus Dam and Judit Vidal-Gonz{\'a}lez and Avik Majumdar and Carmen Pic{\'o}n and Daniel Toth and Anna Darnell and Abraldes, \{Juan G.\} and Marta L{\'o}pez and Christian Jansen and Johannes Chang and Robert Schierwagen and Frank Uschner and Guido Kukuk and Carsten Meyer and Daniel Thomas and Karsten Wolter and Strassburg, \{Christian P.\} and Wim Laleman and \{La Mura\}, Vincenzo and Cristina Ripoll and Annalisa Berzigotti and Calleja, \{Jos{\'e} Luis\} and Puneeta Tandon and Virginia Hernandez-Gea and Thomas Reiberger and Agust{\'i}n Albillos and Tsochatzis, \{Emmanuel A.\} and Aleksander Krag and Joan Genesc{\`a} and Jonel Trebicka and \{Baveno VI (Baveno Cooperation)\}",

year = "2020",

month = jun,

doi = "10.1016/j.jhep.2019.12.021",

language = "English",

volume = "72",

pages = "1140--1150",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "Elsevier",

number = "6",

}

Praktiknjo, M, Simón-Talero, M, Römer, J, Roccarina, D, Martínez, J, Lampichler, K, Baiges, A, Low, G, Llop, E, Maurer, MH, Zipprich, A, Triolo, M, Maleux, G, Fialla, AD, Dam, C, Vidal-González, J, Majumdar, A, Picón, C, Toth, D, Darnell, A, Abraldes, JG, López, M, Jansen, C, Chang, J, Schierwagen, R, Uschner, F, Kukuk, G, Meyer, C, Thomas, D, Wolter, K, Strassburg, CP, Laleman, W, La Mura, V, Ripoll, C, Berzigotti, A, Calleja, JL, Tandon, P, Hernandez-Gea, V, Reiberger, T, Albillos, A, Tsochatzis, EA , Krag, A, Genescà, J, Trebicka, J & Baveno VI (Baveno Cooperation) 2020, 'Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis', Journal of Hepatology, bind 72, nr. 6, s. 1140-1150. https://doi.org/10.1016/j.jhep.2019.12.021

TY - JOUR

T1 - Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis

AU - Praktiknjo, Michael

AU - Simón-Talero, Macarena

AU - Römer, Julia

AU - Roccarina, Davide

AU - Martínez, Javier

AU - Lampichler, Katharina

AU - Baiges, Anna

AU - Low, Gavin

AU - Llop, Elba

AU - Maurer, Martin H.

AU - Zipprich, Alexander

AU - Triolo, Michela

AU - Maleux, Geert

AU - Fialla, Annette Dam

AU - Dam, Claus

AU - Vidal-González, Judit

AU - Majumdar, Avik

AU - Picón, Carmen

AU - Toth, Daniel

AU - Darnell, Anna

AU - Abraldes, Juan G.

AU - López, Marta

AU - Jansen, Christian

AU - Chang, Johannes

AU - Schierwagen, Robert

AU - Uschner, Frank

AU - Kukuk, Guido

AU - Meyer, Carsten

AU - Thomas, Daniel

AU - Wolter, Karsten

AU - Strassburg, Christian P.

AU - Laleman, Wim

AU - La Mura, Vincenzo

AU - Ripoll, Cristina

AU - Berzigotti, Annalisa

AU - Calleja, José Luis

AU - Tandon, Puneeta

AU - Hernandez-Gea, Virginia

AU - Reiberger, Thomas

AU - Albillos, Agustín

AU - Tsochatzis, Emmanuel A.

AU - Krag, Aleksander

AU - Genescà, Joan

AU - Trebicka, Jonel

AU - Baveno VI (Baveno Cooperation)

PY - 2020/6

Y1 - 2020/6

N2 - BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.METHODS: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.RESULTS: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm 2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02-2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA. CONCLUSION: This study suggests that TSA >83 mm 2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. LAY SUMMARY: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.

AB - BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.METHODS: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.RESULTS: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm 2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02-2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA. CONCLUSION: This study suggests that TSA >83 mm 2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. LAY SUMMARY: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.

KW - ACLF

KW - Acute decompensation

KW - Acute-on-chronic liver failure

KW - Ascites

KW - Cirrhosis

KW - Computed tomography

KW - Hepatic encephalopathy

KW - Liver

KW - Portal hypertension

KW - Spontaneous portosystemic shunt

KW - SPSS

KW - TIPS

U2 - 10.1016/j.jhep.2019.12.021

DO - 10.1016/j.jhep.2019.12.021

M3 - Journal article

C2 - 31954206

AN - SCOPUS:85081204806

SN - 0168-8278

VL - 72

SP - 1140

EP - 1150

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 6

ER -

Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis

Abstract

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