ASAIO Journal 2024 Clinical Critical Care
Development and First Clinical Use of an Extracorporeal
Artificial Multiorgan System in Acute-on-Chronic Liver Failure
Patients
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Suhail Ahmad,* Alexander Novokhodko ,† Iris W. Liou,* Nancy Colobong Smith,‡ Robert L. Carithers,* Jorge Reyes,§
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Ramasamy Bakthavatsalam,§ Carl Martin,¶ Renuka Bhattacharya,* Nanye Du,† Shaohang Hao,† and Dayong Gao†
Multiple organ failure (MOF) is a common and deadly condition.
Patients with liver cirrhosis with acute-on-chronic liver failure
(AOCLF) are particularly susceptible. Excess fluid accumula-
tion in tissues makes routine hemodialysis generally ineffective
because of cardiovascular instability. Patients with three or more
organ failures face a mortality rate of more than 90%. Many
cannot survive liver transplantation. Extracorporeal support
systems like MARS (Baxter, Deerfield, IL) and Prometheus (Bad
Homburg, Germany) have shown promise but fall short in bridg-
ing patients to transplantation. A novel Artificial Multi-organ
*From the Department of Medicine, University of Washington, Seattle,
Washington; †Department of Mechanical Engineering, University of
Washington, Seattle, Washington; ‡School of Nursing, University of
Washington, Seattle, Washington; §Department of Surgery, University
of Washington, Seattle, Washington; and ¶Department of Clinical
Engineering, University of Washington, Seattle, Washington.
Submitted for consideration September 2023; accepted for publica-
tion in revised from February 2024.
Disclosure: The authors have no conflicts of interest to report.
D.G. received the Origincell Endowment funding and other gift funds
from the University of Washington. A.N. received funding from the
National Science Foundation Graduate Research Fellowship Program
and the Ron and Wanda Crockett Endowed Fellowship in Mechanical
Engineering. The work was also supported by a grant from the Bronco
Family. Funding sources played no role in the design of the study, data
collection, analysis, or interpretation. Funding sources played no role
in the writing of the manuscript.
Supplemental digital content is available for this article. Direct URL
citations appear in the printed text, and links to the digital files are
provided in the HTML and PDF versions of this article on the journal’s
Web site (www.asaiojournal.com).
S.A. treated patients, devised the AMOR system, and wrote the man-
uscript. A.N. devised and conducted in vitro experiments and wrote
the manuscript. I.L. treated patients. N.C.S. treated patients and pre-
pared training materials for other staff. R.C. treated patients. J.R. treated
patients. R.B. treated patients. N.D. devised and conducted in vitro
experiments. S.H. revised the manuscript and analyzed the data. D.G.
contributed to conceptualization, methodology, supervision, data
analysis, manuscript revision, and funding acquisition of the AMOR
research. All authors read and approved the final manuscript.
The use of the new system was authorized by a group of institutional
committees including Directors of the Institutional Review Board,
Risk Management Committee, Transplantation Services, Hepatology,
and Clinical Engineering among others, with the informed consent of
the patient or the family members of those with acute decompensated
cirrhosis with multiorgan failure and on ventilatory support in the
Intensive Care Unit of the University of Washington Medical Center.
Consent to publish was obtained from participants or their
representatives.
The datasets used or analyzed during the current study are available
from the corresponding author on reasonable request.
Correspondence: Suhail Ahmad, University of Washington, Seattle,
Washington. Email: sahmad@uw.edu. Dayong Gao, University of
Washington, Seattle, Washington. Email: dayong@uw.edu.
Copyright © ASAIO 2024
DOI: 10.1097/MAT.0000000000002174
1
Copyright © ASAIO 2024
Replacement System (AMOR) was developed at the University
of Washington Medical Center. AMOR removes protein-
bound toxins through a combination of albumin dialysis, a
charcoal sorbent column, and a novel rinsing method to pre-
vent sorbent column saturation. It removes excess fluid through
hemodialysis. Ten AOCLF patients with over three organ failures
were treated by the AMOR system. All patients showed signifi-
cant clinical improvement. Fifty percent of the cohort received
liver transplants or recovered liver function. AMOR was suc-
cessful in removing large amounts of excess body fluid, which
regular hemodialysis could not. AMOR is cost-effective and
user-friendly. It removes excess fluid, supporting the other vital
organs such as liver, kidneys, lungs, and heart. This pilot study’s
results encourage further exploration of AMOR for treating
MOF patients. ASAIO Journal 2024; XX:XX–XX
Key Words: albumin dialysis, liver failure, liver support system,
multiorgan failure
In acutely ill patients, multiple organ failure (MOF) is preva-
lent and has increased over the last decades.1 The overall mor-
tality risk increases when multiple vital organs fail. The failure
of vital organs such as liver, kidney, heart, brain, and lungs is
common. Treatment of these organ failures requires a complex
array of life support equipment, including but not limited to
mechanical ventilatory support, continuous renal replacement
therapy (CRRT), and circulatory support with vasoconstrictors.
Specially trained staff are needed for extracorporeal treatment.
This raises treatment costs and potential risks. There is a press-
ing need for a single, user-friendly extracorporeal system to
support failing organs, especially as organ failure severity rises,
and conventional support methods often fall short.2,3
Patients with acute worsening liver function often experi-
ence MOF. The prognosis with three or more organ system fail-
ures is extremely poor. 28-day mortality is 75%–90%.4,5 The
outcome is particularly poor in those who have renal failure
requiring dialysis.3 Similarly, Model for End-stage Liver Disease
(MELD) score of >35 is associated with a mortality of 80%, and
Sequential Organ Failure Assessment (SOFA) score of over 11
has a mortality risk of 80%–100%.4,6
Kidney dialysis is usually effective in treating the biochemi-
cal abnormalities of renal failure, such as urea, creatinine,
electrolyte abnormalities, and metabolic acidosis. However,
renal dialysis often fails to treat the significant accumulation
of extracellular fluid (ECF) in liver failure patients. This ECF
excess is a barrier to transplantation and adversely affects pul-
monary, cardiac, and neurologic functions, along with patient
outcomes.7 Renal dialysis cannot reduce the concentration of
protein-bound hepatic toxins such as bilirubin.8
 2 AHMAD ET AL.
We studied AOCLF instead of acute liver failure (ALF)
because the course of the disease is better defined, the patient
population is more homogenous, and in the United States,
there are many more AOCLF patients than ALF patients. ALF
accounted for only 1.9% of US transplant candidates in 2021.9
Several systems based on the concept of using albumin-
containing dialysate to remove albumin-bound toxins have
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been developed. The Molecular Adsorbent Recirculating
System (MARS) is the only extracorporeal liver support system
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currently approved by the Food and Drug Administration (FDA)
in the United States.10 Two small randomized controlled tri-
als (RCTs) supported the use of MARS to improve survival in
AOCLF patients.11,12 However, two large RCTs did not show
improved survival or transplantation rates.13,14 In these large
RCTs, MARS reduced protein-bound and water-soluble toxins,
however improvements in hepatic encephalopathy, length of
hospital stay, and mechanical ventilation requirement did not
consistently attain statistical significance.
Past work from our group established two key observations.
First, albumin dialysate removes protein-bound toxins across
commonly used dialyzer membranes, eliminating the neces-
sity for a specially designed membrane like the one reported
for MARS.15 Second, charcoal columns can regenerate albu-
min dialysate by removing clinically relevant toxins such as
bilirubin.16
Based on these experiments and in vitro data, we created a
liver dialysis system with recirculating and regenerating albu-
min dialysate. The combined hemodialysis (HD) and albumin
dialysate system provides both liver and kidney dialysis. Our
experience and in vitro experiments show that the charcoal
column rapidly loses its efficiency. Thus, unlike previous sys-
tems, our device allows sorbent columns to be regenerated to
maintain their functionality. This novel Artificial Multi-organ
Replacement System (AMOR) has been used in critically ill
liver failure patients with grade 4 encephalopathy on ventila-
tor and vasopressor support requiring HD for kidney failure.
Results of the in vitro studies and the use of AMOR in 10 criti-
cally ill patients are presented in this manuscript.
Materials and Methods
In Vitro Studies
The in vitro studies were based on our prior work using a
benchtop model that showed that albumin dialysate can remove
bilirubin from “blood side solution” and charcoal columns can
regenerate albumin dialysate.15–17 In addition, negative control
experiments were added, without any albumin on the “dialysate
side” to determine the capacity of pure dialysate to remove tox-
ins. Experiments were also conducted to test the possibility of
regenerating used charcoal columns, to increase their efficient
life. The Supplementary Methods, Supplemental Digital Content
1, http://links.lww.com/ASAIO/B233, include reagent purities
and purchasing information and assay design information.
Benchtop Setup
The setup, detailed elsewhere,15 involved a dialyzer with
dialysate fluid flowing through both blood and dialysate sides.
Bovine serum albumin (BSA) was added to the blood side at
2 g/dL, a clinically relevant level for severe liver failure.18 Toxins
Copyright © ASAIO 2024
(listed below) were added at concentrations reflecting those
found in the blood of liver failure patients. The blood side and
dialysate side flow rates were 150 ml/min. For BSA dialysis,
the dialysate side had 2 g/dL BSA, while the negative control
had no BSA. BSA was chosen because it has 76% homology to
human serum albumin (HSA) and is frequently used as a lower-
cost substitute.19 Differences between human and bovine albu-
min may be a confounding factor. The dialyzers used were the
Fresenius F3 dialyzer (polysulfone, surface area 0.4 m2). For
the in vitro work only, dialyzers were cleaned and reused after
clinical protocols.20,21 The solutions’ pH was adjusted between
7.35 and 7.45 using NaOH and HCl. pH was measured by a
pH meter (OrionStar A211, Thermo Scientific, Waltham, MA).
Pressure was measured by Omega PX409 or Honeywell RSC
sensors. The blood and dialysate reservoirs were immersed in
a 37 °C water bath (Benchmark, Sayreville, NJ). The trial dura-
tion was five hours.
Toxins
Blood side solution contained BSA, bilirubin, cholic acid,
creatinine, indoxyl sulfate, copper, and manganese dissolved
in dialysate. These toxins have distinct BSA binding sites.22–25
Including multiple toxins accurately represented the complex
milieu of liver failure. For this study, bilirubin was measured
and reported. Bilirubin was dissolved as previously described
using dimethylsulfoxide (DMSO) and sodium carbonate.17
Bilirubin initial concentration was approximately 20 mg/dL in
the benchtop setup.17 In regeneration trials, a bilirubin concen-
tration of approximately 10 mg/dL was chosen to mimic used
albumin dialysate from the benchtop trials.
Detoxification of Toxin Containing BSA
Solution by Charcoal Column
Figure 1 shows a schematic of our charcoal column setup
to test the efficacy of charcoal column regeneration. Adsorba
300 columns (Baxter) were used to remove toxins from the
dialysate with toxins and BSA. Columns were primed accord-
ing to the instructions. After the priming, the inlet tubing was
placed in 500 ml of BSA dialysate. Priming fluid was discarded
into a waste container until yellow pigment was seen at the
column outlet. Now the system was switched into detoxifica-
tion mode. BSA dialysate was recirculated through the column
for three hours. Samples were taken at the inlet and outlet.
The column dead volume was determined using the volume
of priming fluid.
Charcoal Column Regeneration Using Dialysate Solution
After three hours of toxin-laden BSA flow at 120 ml/min, regen-
eration began at 50 ml/min with outflow to waste for 30 minutes
using dialysate without albumin and toxins. Simultaneously, the
used BSA dialysate in the column was discarded.
After regeneration, the column was reconnected to the
BSA circuit with a 120 ml/min flow rate, with regeneration
fluid discarded to prevent toxin loss in experimental tubing.
Discarding stopped when yellow pigment appeared in the
charcoal column outlet. The discarded volume was used to
measure column dead volume. Once regeneration fluid was
removed, toxin-laden BSA dialysate recirculated for another
three hours.
 ARTIFICIAL MULTIORGAN SYSTEM
Statistics
Unless otherwise noted, comparisons were done using the
unpaired two-tailed Student’s t-test without assuming equal vari-
ance. Calculations were done in Microsoft Excel. A value of P <
0.05 was considered statistically significant. For albumin dialysis
trials, the percent of solute removed was calculated as follows:
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Ci − C (t = 5)
% Removed (t) = 100% ∗
Ci
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where Ci is the solute concentration at time 0. C (t = 5) is the
solute concentration at time t = 5 hours. The concentration at
the dialyzer inlet is used.
Charcoal column regeneration was analyzed using slopes
between the first and last points of specific time periods: “First
Hour” (0–60 minutes), “Pre-regeneration” (120–180 minutes),
and “Post-regeneration” (210–270 minutes). Each set of slopes
was compared using unpaired two-tailed t-tests without assum-
ing equal variance.
System
AMOR System Description. A schematic drawing of
the AMOR system is shown in Figure 2. Patient blood first
flowed through the albumin circuit hemodialyzer (Exeltra
210, Baxter). The albumin circuit contained 2%–4% albumin
dialysate, recirculated at a rate of 20 ml/min. This circuit also
Figure 1. Charcoal column regeneration in vitro test setup. The
main detoxification circuit is in black. The rinsing circuit is in gray.A
circuit showing a container of toxin-containing BSA dialysate, an
albumin dialysate loop, and a charcoal column. A second circuit
showing a bag of regeneration fluid, a charcoal column, and a waste
container, with flow from the regeneration fluid into the waste.
Figure 2. Schematic diagram of the AMOR system. AMOR, Artificial Multi-organ Replacement System.Adiagram showing blood from the
patient entering an albumin dialyzer, then entering a hemodialysis machine (2008 K, Fresenius) and then being returned to the patient. On the
dialysate side of the albumin dialyzer there is the albumin dialysate albumin circuit containing recirculating 2-4% albumin dialysate, a charcoal
column, and the charcoal cleaning circuits.
Copyright © ASAIO 2024
3
included a charcoal column (Adsorba 300, Gambro/Baxter,
Lund, Sweden) which was periodically cleaned. Blood from
the outlet of the albumin dialyzer flowed to a Fresenius 2008K
HD machine, where regular HD was conducted, using Diacap
LOPS15 hemodialyzer (B. Braun, Melsungen, Germany) and
blood and dialysate flow at 200 and 500 ml/min, respectively.
Regeneration of Charcoal Column
The charcoal column was periodically cleaned with 500–
1000 ml of 5% dextrose normal saline solution (D5NS) every
60 minutes. While the charcoal column was rinsed, Albumin
dialysis was on hold, but the HD was continued through the
Fresenius machine.
Clinical Studies
The use of the new AMOR system was authorized, with the
informed consent of either the patient or the family member of
those with acute decompensated cirrhosis with MOF and on
ventilatory support in the Intensive Care Unit of the University
of Washington Medical Center. The University of Washington
Human Subject Division (Institution’s Review Board [IRB])
advised that the proposed work did not require formal IRB
approval. The IRB determined that liver-kidney dialysis was
provided solely for clinical care; it was not performed for
research purposes. IRB approval was granted for specimen and
data collection and analysis. The IRB permitted limited use of
the system in 15 patients. The IRB reviewed the protocol and
consent form.
Patients
The patients were listed for liver transplantation but were
marked inactive on the transplant wait list because of their
unstable clinical condition (Table 1).
All patients had multiorgan involvement (>4 organ system
failures):
1. Kidney failure with large extracellular volume (ECV) of
excess fluid and requiring HD treatment.
2. Central nervous system involvement, in deep coma.
3. Respiratory failure on ventilatory support.
4. Cardiovascular involvement with hypotension requiring
vasopressor support.
5. Hematological system involvement with active bleeding
from multiple sites;
 4 AHMAD ET AL.

Table 1. Patient Demographics

Patient No. Age Gender Days on Transplant List SOFA Score MELD Score

 1 52 F 5 18 39
 2 54 F 17 19 40
 3 53 M 32 19 40
 4 59 F 6 19 34
 5 43 F 35 17 35
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 6 57 F 12 18 34
 7 55 M 27 20 40
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 8 57 F 35 20 39
 9 57 F 28 18 36
 10 55 F 73 19 40
Mean ± SD 54.2 ± 4.5 8:2 (F:M) 27 ± 19.8 18.7 ± 0.9 37.7 ± 2.6

MELD, Model for End-Stage Liver Diseases; SOFA, Sequential Organ Failure Assessment.

All patients had advanced renal failure with massive fluid

overload requiring HD. Despite using various dialytic meth-
ods such as traditional HD, sequential ultrafiltration (UF) and
HD, slow continuous UF (SCUF), or slow low-efficiency HD
(SLED), effective fluid removal was limited due to hemody-
namic instability. Patient characteristics are summarized in
Table 1; average age was 54.2 ± 4.5 (mean ± SD). All had an
SOFA score >16, averaging 18.7 + 0.9 (mean ± SD), and a high
MELD score with a mean of 37.7 + 2.6 (mean ± SD).

Results

In Vitro Experiments
In vitro testing showed that albumin dialysate removes bili-
rubin. Figure 3 shows that bilirubin removal was significantly
greater in albumin (BSA) dialysis than in the control (P = 0.01,
n = 3).
Figure 4 shows bilirubin concentration over time during the
albumin regeneration experiment using the Adsorba 300 char- Figure 4. Change in bilirubin concentration over time before and
after regeneration of charcoal column.A figure showing the decline
coal column. In the first hour of the experiments, the bilirubin of bilirubin concentration over time in the regeneration trial.
concentration declined at a rate of 1.89 mg/hr. Through the hour

“preregeneration,” this rate decreased to 0.48 mg/hr, which is

significantly lower than the first hour (P = 0.0046). During the
hour of “postregeneration,” the concentration declined at a rate
of 1.35 mg/hr. This rate was a significant increase from the “pre-
regeneration” period (P = 0.027). The “post-regeneration” bili-
rubin decline rate did not differ significantly from the first-hour
observation (P = 0.22). The dead volume of the charcoal column
discarded during regeneration was 207 ml ± 12 ml. For concen-
tration decline measurements, five experiments were conducted.

Figure 3. From the blood side to dialysate more than 5 hours. The
negative control is dialysate without BSA. N = 3. The symbol * indi-
cates BSA dialysis removed significantly more bilirubin than dialy-
sate without BSA (P ≈ 0.01); values are mean ± standard deviation.
BSA, bovine serum albuminA figure showing that the BSA dialysate
removes significantly more bilirubin than the negative control (dialy-
sate without BSA).
Clinical Outcomes
All patients responded to the AMOR therapy with improve-
ment in hepatic encephalopathy, respiratory function, and
hemodynamic parameters. Ventilatory and vasopressor sup-
ports were no longer needed. Patients lost a significant volume
of extracellular fluid excess. Based on transplantation, patients
fell into two groups (Table 2): in group 1, there were five patients
who either eventually underwent liver transplantation (n = 4) or
recovered liver function (n = 1); in group 2, five patients died
while waiting for a liver transplantation (Figure 5). There were
no significant differences between the two groups in terms of
age, gender, or severity of the disease, SOFA and MELD scores

Copyright © ASAIO 2024

 ARTIFICIAL MULTIORGAN SYSTEM 5

Table 2. AMOR Treatment Data

Patient No. Clinically Improved Received Liver Transplant Total AMOR Treatments Total Weight Loss, kg

    Group 1 Patients received transplants or recovered

 1 Yes Yes 5 5
 2 Yes Yes 11 8
 3 Yes Yes 16 45
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 4 Yes Yes 5 16

 5 Yes No* 11 37
Mean ± SD 9.6 ± 4.7 22.2 ± 17.9
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    Group 2 Patients improved but expired while waiting for a transplant
 6 Yes No 10 34
 7 Yes No 16 20
 8 Yes No 20 33
 9 Yes No 12 13
 10 Yes No 13 16
Mean ± SD 14.2 ± 3.9 23.2 ± 9.7

Clinical Improved: extubated, vasopressors discontinued, recovered from coma.

*Recovered liver function.
AMOR, Artificial Multi-organ Replacement System; SD, standard deviation.

Figure 5. Patient outcomes after AMOR treatment. AMOR, Artificial Multi-organ Replacement System.A flow chart showing patient out-
comes, noting that 4 patients were transplanted, 1 patient recovered without transplantation, and five patients died waiting for livers. Among
the patients that died, clincal improvement, extubation, and an average decline of 23 kg in extracellular fluid was observed. Causes of death
were mostly bleeding (n = 4), sepsis (n = 3), stroke (n = 1) and cardiac arrest (n = 1). Some of the five patients had multiple listed causes of death.

were not different between the two groups (Table 1). The first
group received slightly fewer AMOR treatments than the sec-
ond group (9.6 vs. 14.2, P = 0.12). The patients who did not
survive were on the liver transplant waitlist for an average of 35
days after the initiation of AMOR, with one patient waiting for
73 days before dying from sepsis and bleeding.
was measured at both the inlet and outlet of the liver dialyzer
simultaneously. By subtracting outlet bilirubin from the inlet,
we calculated the bilirubin removed from the blood. The study
revealed a strong positive correlation (r2 = 0.69) between albu-
min concentration and bilirubin movement across the dialyzer
membrane (Figure 6A).

Fluid Removal
Bilirubin Removal with Time of Treatment
AMOR’s fluid removal ability was quite remarkable. All
Total bilirubin concentration in the albumin dialysate was
patients before using AMOR had difficulty in fluid removal
measured at the inlet and outlet dialysate of the liver dia-
with usual dialytic techniques, including intermittent renal
lyzer at start, 30 minutes, 4, 6, and 10 hours of treatment. As
replacement therapy (IRRT), SCUF, or SLED. Often, weight loss
expected, inlet bilirubin increased from zero at the start and
was minimal (<0.4 Kg), or they gained weight due to IV fluids
continued to rise. However, post-dialyzer bilirubin concentra-
for intra-dialytic hypotension. In the same patients with AMOR
tion remained higher with a positive delta value (postdialyzer
treatment, ultrafiltration was well tolerated even at a rate of 1 L/
minus predialyzer concentration). As seen in Figure 6B, the dif-
hr (upper limit set by the protocol). The range of fluid weight
ference between the inlet and outlet concentration decreased
loss was 5–45 kg (Table 2) with an average loss of 22.7 kg.
with time representing the effect of saturation of binding sites
and decrease in gradient.
Dialysate Albumin and Bilirubin Removal
The relationship between dialysate albumin concentration
Discussion
and total bilirubin removal was studied in two patients. Varying
dialysate albumin concentration was used during 17 proce- The present article has two components, in vitro experi-
dures. The concentration ranged from 2.1–3.92 g/dL. Bilirubin ments, and clinical observations in a small number of patients

Copyright © ASAIO 2024

 6 AHMAD ET AL.
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Figure 6. A: Relationship between dialysate albumin and bilirubin removal in patients undergoing liver dialysis. Two values where data
points are plotted together shown as (2). B: Delta bilirubin concentration in the albumin dialysate. Delta bilirubin concentration is defined as
(postdialyzer, concentration minus predialyzer concentration). It is plotted against the duration of the AMOR treatment. N = 19 sessions in
two patients. r = 0.69. P < 0.05. AMOR, Artificial Multi-organ Replacement System.A figure with two panels. On panel A, the reduction in bili-
rubin concentration is compared to the dialysate albumin concentration, showing a trend towards more bilirubin removal at higher dialysate
albumin concentration (N = 17). In panel B, the delta bilirubin concentration during a single pass through the liver dialyzer is shown over time
during a treatment (N = 19).

with extremely poor prognosis. In vitro experiments reveal that
dialysate containing albumin is effective in bilirubin removal,
while dialysate without albumin is ineffective (Figure 3). In
vitro experiments also show that a charcoal column can regen-
erate albumin dialysate by removing bilirubin. The efficiency
of charcoal columns, in terms of bilirubin removal, declines
with time, however, rinsing the column restores its efficiency
(Figure 4).
MOF involving the lungs, heart, and kidney is commonly
seen in intensive care patients. The prognosis worsens with
increasing number of organ system failures. In one report,
over 50% of ICU deaths occur despite advanced organ sup-
port.26 During the recent COVID-19 pandemic, MOF mortal-
ity surged by 341%.27 Critically ill patients are treated using
various machines to support their failing kidneys, liver, heart,
and lungs. This article presents a prototype system that inte-
grates kidney and liver support while managing excess fluid
and blood acid-base abnormalities.
AMOR was used in patients with AOCLF with failure of
other organs where standard dialysis treatment was not able
to control fluid excess that complicated pulmonary function
and hemodynamic stability. The patients who were treated
had potential risk of high mortality. A 28-day survival of less
than 25%5,28 is reported in such patients. With the deteriora-
tion in clinical condition, patients become too unstable for
liver transplantation. Various dialysis methods, including char-
coal hemodetoxification, IRRT, CRRT, and standard plasma
exchange, proved ineffective in improving the odds of being
transplanted in AOCLF patients.5,29–31 Devices like MARS and
Prometheus showed clinical and biochemical improvements
but lacked consistent success as bridges to liver transplants in
AOCLF with MOF.13,14,29,32–35
AMOR Has Many Advantages Over MARS
1. Cost-effective: AMOR uses readily available pumps
and tubes, significantly lowering both initial setup and
ongoing disposable costs. MARS costs approximately
$24,000 more than AMOR’s off-the-shelf components.
2. Affordable treatment: MARS incurs a per-treatment cost
of around $3,000, while AMOR’s cost is roughly $700.
AMOR’s treatment closely resembles standard HD, sim-
plifying staff training and reducing associated expenses.
3. Efficient combination: AMOR uniquely combines albu-
min dialysis with traditional dialysis in a single treatment.
This integrated approach excels at removing excess ECF,
previously unmatched, and reduces the need for addi-
tional costly dialysis sessions.
4. AMOR’s ability to remove fluid improves the pulmonary
and cardiac functions.
Our in vitro results show that the bilirubin removal rate
declined within 2 hours of use, but was restored through
regeneration (Figure 4). We introduced a periodic rinse of
the charcoal column during clinical use. The hourly rinse
with dialysate initially produced dark yellow fluid, gradually
lightening. This novel design worked very well without any
complications. Future research should quantify its impact on
maintaining charcoal column efficiency.
A recent device, ADVOS (Advitos, Munich, Germany), has
been used for critically ill MOF patients. It provides liver, kid-
ney, and lung support. It aims to regenerate albumin in the
dialysate through pH modulation and filter out waste like bili-
rubin via ultrafiltration. While pH modulation is believed to
aid the patient’s acid-base balance,36,37 data regarding bilirubin
removal is lacking and contradicts some reports.38 Although
biomarkers show improvement, no clear survival benefit has
been demonstrated.39
We have presented a multiorgan support system that
achieved 28-day survival of 80% in very ill patients (Tables 1
and 2) compared to 25% expected 28-day survival in
published reports in AOCLF with >3 organ failures.4 Ten
patients with severe AOCLF, requiring life-sustaining mea-
sures like ventilation, vasopressors, and dialysis, saw sig-
nificant improvement with AMOR. This included extubation,

Copyright © ASAIO 2024

 ARTIFICIAL MULTIORGAN SYSTEM
vasopressor discontinuation, and significant fluid loss. One
of the most striking effects of AMOR was its ability to per-
form ultrafiltration without causing hemodynamic instabil-
ity. Patients who couldn’t tolerate this with traditional HD
or CRRT managed ultrafiltration rates as high as 12 ml/kg/
hour, possibly due to substances removed by the Albumin
Dialysis segment preventing blood pressure drops. The rea-
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son for this difference between traditional HD and AMOR
requires further investigation. It may have been a result of the
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 03/04/2024
removal of some vaso-depressant substance by the Albumin
Dialysis segment preventing the significant drops in blood
pressure. This aligns with the theory that plasma exchange
improves the condition of ALF patients by clearing vaso-
depressant molecules, such as DAMPs, soluble B7 (CD80,
86) or angiopectins.34,35 Fluid removal enhances eligibility
for liver transplantation.
The system was used in over 120 procedures, with no seri-
ous adverse treatment-related events that required interruption
or discontinuation of treatment. When AMOR was started,
active bleeding in all patients improved significantly; however,
five patients developed bleeding or disseminated infections
between 12 and 74 days after completion of AMOR therapy,
while on the active liver transplant waitlist. These complica-
tions have been reported in the literature with the use of extra-
corporeal devices.5
In this limited study, the 80% 28-day survival rate and suc-
cessful bridge to transplantation or recovery in half of criti-
cally ill patients is very promising and warrants testing on a
larger number of patients. This degree of success in critically ill
patients has not been reported before.
Limitations
The study’s main limitation is its small sample size and absence
of a control group. It has been observed that clinical trial proce-
dures “result in an increased number of measurements of vital
signs as well as biochemical parameters, and an increased num-
ber of hours in which physicians and nurses are in close proxim-
ity to the patients.”40 Thus, outperforming historical data does not
confirm a system’s superiority. An RCT is needed. Additionally,
this trial could not be blinded, introducing the risk of bias. A
sham procedure in a human trial control group would raise
ethical questions, though animal trials of artificial liver support
systems have used sham devices to permit blinding in the past.
Initial results suggest AMOR should be further studied as a bridge
to liver transplantation in a larger group with advanced AOCLF.
Future Research
This work needs to be confirmed through appropriately
powered RCTs. Additionally, the physiologic mechanisms of
the enhanced ability of the AMOR system to remove excess
fluid from critically ill patients need to be studied. Techniques
such as metabolomics, the development of an in vitro model
of blood vessels in liver failure, and benchtop studies on
the ability of albumin dialysis to remove known vasoactive
compounds may shed light on this question. Finally, AMOR
needs to be designed for mass production and use outside of
the carefully controlled environment of a clinical trial. Long-
term objectives include the design of a portable system for
emergency medicine, casualty evacuation, and home use.
Copyright © ASAIO 2024
7
Acknowledgment
This work was supported, in part, by the Origincell Endowment
and other gift funds from University of Washington. We are grate-
ful to the University of Washington Medical Center dialysis lab for
Adsorba 300 columns. This work was also supported by the National
Science Foundation Graduate Research Fellowship Program grant DGE-
1762114. Any opinions, findings, and conclusions or recommendations
expressed in this material are those of the author(s) and do not necessar-
ily reflect the views of the National Science Foundation. We acknowl-
edge the Kidney Dialysis Pheresis Services Office at the University of
Washington Medical Center for providing materials for this research.
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