Biomedical Engineering Reference
In-Depth Information
substrates to flow down their gradient over the membrane where they are tran-
siently bound by albumin in the secondary circuit [
61
].The low-molecular-weight
substrate is then removed from the system by conventional dialysis and hemo-
diafiltration within the secondary circuit.
The initial clinical study described a series of 13 patients who underwent
treatment after failure of response to best medical therapy for acute-on-chronic
hepatic failure. In this series, the overall survival was 69 % and the authors cited
that all patients showed a positive response to therapy [
62
]. Other encouraging
case reports and small studies eventually led to more widespread use of the system.
To date, roughly 7,500 patients have been treated with MARS for various hepatic
diseases, including acute liver failure patients. A meta-analysis assessing the use of
MARS looked at four randomized controlled trials including a total of 67 patients
and two selected nonrandomized trials including 61 patients [
63
]. Patients had
either acute or acute-on-chronic liver failure. Primary meta-analysis did not show a
statistically significant survival benefit. Recently, the results of a large multicenter
randomized trial of MARS in patients with ALF fulfiling high-urgency liver-
transplant criteria in France were presented [
64
]. The data showed a trend toward
better surivival in the MARS treatment group, but the difference did not reach
significance. The transplant-free 6 month survival, however, was significantly
prolonged in those patients treated with at least three sessions of MARS. ''Pro-
metheus
TM
, which employs fractionated plasma separation, is a close variant of
MARS. While MARS is a two-circuit system separated by an albumin imper-
meable membrane, Prometheus utilizes a membrane with a 250 kDa cutoff
between circuits, thereby making the membrane permeable to albumin and hence
albumin-bound toxins. While a large portion of the toxins, which accumulate
during liver failure are water soluble, many are still bound by albumin. Therefore
fractionated plasma separation may be advantageous in regard to toxin removal.
Other factors that distinguish Prometheus from MARS include the fact that while
MARS is prefilled with 120 g of exogenous human albumin, the patient's
endogenous albumin loads the secondary circuit in Prometheus. Because Prome-
theus is loaded with the patient's albumin, there may be a drop in the patient's
albumin levels during treatment [
65
,
66
].
Most of the clinical data involving Prometheus are either uncontrolled or ret-
rospective. A controlled trial, published as an abstract, looking at the effect of
fractionated plasma separation on hepatic encephalopathy, demonstrated that a 6 h
treatment course improved clinical grade and sensory-evoked potentials [
67
].
Multiple case series describe both, acute and acute-on-chronic liver failure patients
being treated with Prometheus. Only recently, the results of a controlled ran-
domized multicenter clinical trial in 145 patients with acute on chronic liver failure
were reported in abstract form [
68
]. Survival rates after 1 and 3 month were not
significantly different in the treated versus the control group. However, patients
with hepatorenal syndrome type I and MELD score of [30 showed a significant
survival benefit. Currently available data thus illustrate a need for new prospective
randomized controlled trials to clarify indications and clinical impact of extra-
corporeal artificial liver support devices.
