High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial.
OBJECTIVE
Acute liver failure (ALF) often 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 frozen plasma in case series improves systemic, cerebral and splanchnic parameters.


METHODS
In this prospective, randomised, controlled, multicentre 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 endpoint was liver transplantation-free survival during hospital stay. Secondary-endpoints 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 vs. 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.
Department of Hepatology, Rigshospitalet, Copenhagen, Denmark. Electronic address: stolze@post3.tele.dk.
Fin Stolze
FS
Larsen
Department of Hepatology, Rigshospitalet, Copenhagen, Denmark.
Lars Ebbe
LE
Schmidt
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Christine
C
Bernsmeier
Department of Surgery and Liver Transplantation C, Rigshospitalet, Copenhagen, Denmark.
Allan
A
Rasmussen
Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Finland.
Helena
H
Isoniemi
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Vishal C
VC
Patel
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Evangelos
E
Triantafyllou
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
William
W
Bernal
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Georg
G
Auzinger
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Debbie
D
Shawcross
Department of Hepatology, Rigshospitalet, Copenhagen, Denmark.
Martin
M
Eefsen
Department of Hepatology, Rigshospitalet, Copenhagen, Denmark.
Peter Nissen
PN
Bjerring
Department of Hepatology, Rigshospitalet, Copenhagen, Denmark.
Jens Otto
JO
Clemmesen
Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Finland.
Krister
K
Hockerstedt
Department of Anaestesia AN-2041, Rigshospitalet, Copenhagen, Denmark.
Hans-Jørgen
HJ
Frederiksen
Department of Hepatology, Rigshospitalet, Copenhagen, Denmark.
Bent Adel
BA
Hansen
Institute of Liver Studies, King's College Hospital, London, United Kingdom; Section of Hepatology, St. Mary's Hospital, Imperial College London, London, UK.
Charalambos G
CG
Antoniades
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Julia
J
Wendon
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D017114:Liver Failure, Acute / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D011446:Prospective Studies
D016207:Cytokines
Ammonia; Artificial liver support; Cerebral oedema; Fulminant hepatic failure; Hepatic encephalopathy; Liver transplantation; Multiorgan failure; Plasmapheresis; Sepsis