High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial

Fin Stolze Larsen; Lars Ebbe Schmidt; Christine Bernsmeier; Allan Rasmussen; Helena Isoniemi; Vishal Patel; Evangelos Triantafyllou; William Bernal; Georg Auzinger; Debbie Shawcross; Martin Eefsen; Peter Nissen Bjerring; Jens Otto Clemmesen; Krister Hockerstedt; Hans-Jørgen Frederiksen; Bent Adel Hansen; Charalambos G Antoniades; Julia Wendon

doi:10.1016/j.jhep.2015.08.018

High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial

Fin Stolze Larsen, Lars Ebbe Schmidt, Christine Bernsmeier, Allan Rasmussen, Helena Isoniemi, Vishal Patel, Evangelos Triantafyllou, William Bernal, Georg Auzinger, Debbie Shawcross, Martin Eefsen, Peter Nissen Bjerring, Jens Otto Clemmesen, Krister Hockerstedt, Hans-Jørgen Frederiksen, Bent Adel Hansen, Charalambos G Antoniades, Julia Wendon

Inflammation Biology

Research output: Contribution to journal › Article › peer-review

486 Citations (Scopus)

Abstract

BACKGROUND: Acute liver failure (ALF) results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15% of ideal body weight with fresh fozen plasmain case series improves systemic, cerebral and splanchnic parameters.

METHODS: In this prospective, randomised, controlled, multicenter trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT;90 patients) or SMT plus HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary end point was liver transplantation-free survival during hospital stay. Secondary-end-points included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken.

RESULTS: For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP versus 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95% confidence interval (CI),0.36-0.86;P=0.0083). HVP prior to transplantation did not improve survival compared with patients who received SMT alone (CI 0.37 to 3.98; P = 0.75). The incidence of severe adverse events was similar in the two groups. Systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (P<0.001).

CONCLUSIONS: Treatment with HVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction (MOF). (ClinicalTrials.gov number NCT00950508).

Original language	English
Pages (from-to)	69-78
Journal	Journal of Hepatology
Volume	64
Issue number	1
Early online date	29 Aug 2015
DOIs	https://doi.org/10.1016/j.jhep.2015.08.018
Publication status	Published - 1 Jan 2016

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10.1016/j.jhep.2015.08.018

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Larsen, F. S., Schmidt, L. E., Bernsmeier, C., Rasmussen, A., Isoniemi, H., Patel, V., Triantafyllou, E., Bernal, W., Auzinger, G., Shawcross, D., Eefsen, M., Bjerring, P. N., Clemmesen, J. O., Hockerstedt, K., Frederiksen, H.-J., Hansen, B. A., Antoniades, C. G., & Wendon, J. (2016). High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. Journal of Hepatology, 64(1), 69-78. https://doi.org/10.1016/j.jhep.2015.08.018

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title = "High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial",

abstract = "BACKGROUND: Acute liver failure (ALF) results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15% of ideal body weight with fresh fozen plasmain case series improves systemic, cerebral and splanchnic parameters.METHODS: In this prospective, randomised, controlled, multicenter trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT;90 patients) or SMT plus HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary end point was liver transplantation-free survival during hospital stay. Secondary-end-points included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken.RESULTS: For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP versus 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95% confidence interval (CI),0.36-0.86;P=0.0083). HVP prior to transplantation did not improve survival compared with patients who received SMT alone (CI 0.37 to 3.98; P = 0.75). The incidence of severe adverse events was similar in the two groups. Systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (P<0.001).CONCLUSIONS: Treatment with HVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction (MOF). (ClinicalTrials.gov number NCT00950508).",

author = "Larsen, {Fin Stolze} and Schmidt, {Lars Ebbe} and Christine Bernsmeier and Allan Rasmussen and Helena Isoniemi and Vishal Patel and Evangelos Triantafyllou and William Bernal and Georg Auzinger and Debbie Shawcross and Martin Eefsen and Bjerring, {Peter Nissen} and Clemmesen, {Jens Otto} and Krister Hockerstedt and Hans-J{\o}rgen Frederiksen and Hansen, {Bent Adel} and Antoniades, {Charalambos G} and Julia Wendon",

note = "Copyright {\textcopyright} 2015. Published by Elsevier B.V.",

year = "2016",

month = jan,

day = "1",

doi = "10.1016/j.jhep.2015.08.018",

language = "English",

volume = "64",

pages = "69--78",

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Larsen, FS, Schmidt, LE, Bernsmeier, C, Rasmussen, A, Isoniemi, H, Patel, V , Triantafyllou, E, Bernal, W, Auzinger, G, Shawcross, D, Eefsen, M, Bjerring, PN, Clemmesen, JO, Hockerstedt, K, Frederiksen, H-J, Hansen, BA, Antoniades, CG & Wendon, J 2016, 'High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial', Journal of Hepatology, vol. 64, no. 1, pp. 69-78. https://doi.org/10.1016/j.jhep.2015.08.018

TY - JOUR

T1 - High-volume plasma exchange in patients with acute liver failure

T2 - An open randomised controlled trial

AU - Larsen, Fin Stolze

AU - Schmidt, Lars Ebbe

AU - Bernsmeier, Christine

AU - Rasmussen, Allan

AU - Isoniemi, Helena

AU - Patel, Vishal

AU - Triantafyllou, Evangelos

AU - Bernal, William

AU - Auzinger, Georg

AU - Shawcross, Debbie

AU - Eefsen, Martin

AU - Bjerring, Peter Nissen

AU - Clemmesen, Jens Otto

AU - Hockerstedt, Krister

AU - Frederiksen, Hans-Jørgen

AU - Hansen, Bent Adel

AU - Antoniades, Charalambos G

AU - Wendon, Julia

PY - 2016/1/1

Y1 - 2016/1/1

N2 - BACKGROUND: Acute liver failure (ALF) results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15% of ideal body weight with fresh fozen plasmain case series improves systemic, cerebral and splanchnic parameters.METHODS: In this prospective, randomised, controlled, multicenter trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT;90 patients) or SMT plus HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary end point was liver transplantation-free survival during hospital stay. Secondary-end-points included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken.RESULTS: For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP versus 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95% confidence interval (CI),0.36-0.86;P=0.0083). HVP prior to transplantation did not improve survival compared with patients who received SMT alone (CI 0.37 to 3.98; P = 0.75). The incidence of severe adverse events was similar in the two groups. Systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (P<0.001).CONCLUSIONS: Treatment with HVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction (MOF). (ClinicalTrials.gov number NCT00950508).

AB - BACKGROUND: Acute liver failure (ALF) results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15% of ideal body weight with fresh fozen plasmain case series improves systemic, cerebral and splanchnic parameters.METHODS: In this prospective, randomised, controlled, multicenter trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT;90 patients) or SMT plus HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary end point was liver transplantation-free survival during hospital stay. Secondary-end-points included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken.RESULTS: For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP versus 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95% confidence interval (CI),0.36-0.86;P=0.0083). HVP prior to transplantation did not improve survival compared with patients who received SMT alone (CI 0.37 to 3.98; P = 0.75). The incidence of severe adverse events was similar in the two groups. Systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (P<0.001).CONCLUSIONS: Treatment with HVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction (MOF). (ClinicalTrials.gov number NCT00950508).

U2 - 10.1016/j.jhep.2015.08.018

DO - 10.1016/j.jhep.2015.08.018

M3 - Article

C2 - 26325537

SN - 0168-8278

VL - 64

SP - 69

EP - 78

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 1

ER -

High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial

Abstract

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