Invest Clin 67(2): 230 - 240, 2026 https://doi.org/10.54817/IC.v67n2a06

Corresponding author: Huafen Zhang. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; Department of Nursing, The

First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Rd., Shangcheng District, Hang-

zhou City 310003, Zhejiang province, China. Tel: +86-13757120681. Email: zhanghuafen@zju.edu.cn

Impact of plasma adsorption volumes

(5 L vs. 6 L) on the prognosis of patients

with liver failure.

Xin Zhang, Zhuoyao Zhang, Hui Chen and Huafen Zhang

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative

Innovation Center for Diagnosis and Treatment of Infectious Diseases; Department of

Nursing, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou

City, Zhejiang province, China.

Keywords: Plasma Adsorption; Liver Failure; Complications; Duration of Therapy;

Blood Platelets.

Abstract. Plasma adsorption (PA) is used to improve outcomes in liver fail-

ure (LF). Data on adsorption capacity and its relationship to patient outcomes

are limited. This single-center retrospective study included patients with LF

who received PA at the First Affiliated Hospital of Zhejiang University School of

Medicine in Hangzhou City, China, between October 2020 and October 2022,

and examined the impact of adsorption volume (5 L vs. 6 L) on prognosis. The

study included 230 PA treatments, of which nine were excluded due to missing

data. The 5L column was used in 60 patients (118 treatments, 47 male), and

the 6L column was used in 50 patients (103 treatments, 31 male). Treatment

effectiveness was evaluated using length of hospital stay, liver transplantation,

death, and improvement in disease-related symptoms. In both groups, PA in-

creased white blood cells (WBC), international normalized ratio (INR), activated

partial thromboplastin time (APTT), and prothrombin time (PT) but decreased

hemoglobin, total bile acids, total bilirubin, and fibrinogen (all p<0.05). Plate-

let levels decreased after 6L PA (p=0.033) but not after 5L PA (p=0.116). After

PA, the 6L group had lower WBC than the 5L group (p=0.003), but there were

no significant differences in the other parameters. The 5L and 6L columns did

not differ significantly in hospital stay duration, liver transplantation, mortal-

ity, or symptom improvement. However, the 5L column significantly reduced

platelet destruction, shortened treatment time, and reduced the occurrence of

complications, particularly thrombocytopenia-related risks. Hence, the results

indicate that the 5L volume would be preferable clinically.

Plasma adsorption amounts in liver failure 231

Vol. 67(2): 230 - 240, 2026

Impacto de los volúmenes de adsorción plasmática (5 L vs. 6 L)

en el pronóstico de pacientes con insuficiencia hepática.

Invest Clin 2026; 67 (2): 230 – 240

Palabras clave: Adsorción Plasmática; Insuficiencia Hepática; Complicaciones; Duración

de la Terapia; Plaquetas.

Resumen. La adsorción plasmática (AP) se utiliza para mejorar los resulta-

dos en la insuficiencia hepática (IH). Faltan datos relevantes sobre las diferen-

tes capacidades de adsorción y su efecto en la recuperación de los pacientes.

Este estudio retrospectivo unicéntrico incluyó a pacientes con IH que recibie-

ron AP en el First Affiliated Hospital of Zhejiang University School of Medicine,

Hangzhou City, China, entre octubre de 2020 y octubre de 2022, y examinó el

impacto del volumen de adsorción (5 L frente a 6 L) en el pronóstico. El estudio

incluyó 230 tratamientos de AP, de los cuales nueve fueron excluidos por falta

de datos. Se utilizó la columna de 5 L en 60 pacientes (118 tratamientos) y la

de 6 L en 50 pacientes (103 tratamientos). La efectividad se evaluó mediante la

duración de la estancia hospitalaria, el trasplante hepático, la muerte y la me-

joría de los síntomas relacionados con la enfermedad. En ambos grupos, la AP

aumentó los leucocitos, el INR, la APTT y el PT, y disminuyó la hemoglobina, los

ácidos biliares totales, la bilirrubina total y el fibrinógeno (todos p<0,05). Los

niveles de plaquetas disminuyeron después de la AP de 6 L (p=0,033), pero no

con la de 5 L (p=0,116). Tras la AP, el grupo de 6 L mostró leucocitos más bajos

(p=0,003). Las columnas de 5 L y 6 L no mostraron diferencias significativas

en los resultados clínicos principales. Sin embargo, la columna de 5 L redujo

significativamente la destrucción plaquetaria y acortó el tiempo de tratamien-

to, lo que sugiere que el volumen de 5 L podría ser clínicamente preferible.

Received: 08-10-2025 Accepted: 05-03-2026

INTRODUCTION

Liver failure (LF) is the leading cause of

death in patients with liver disease. It often

progresses rapidly, with a poor prognosis and

severe cases that are life-threatening1,2. High

mortality associated with LF results from se-

vere impairment or decompensation of he-

patic synthesis, detoxification, excretion,

and biotransformation functions. Among

these, the accumulation of bile acids, biliru-

bin metabolites, and ammonia in the body is

a major factor 3-5. These metabolites are nor-

mally managed by the liver, and abnormal

liver function can lead to brain dysfunction

(hepatic encephalopathy), renal dysfunc-

tion (hepatorenal syndrome), and eventually

death 6, 7.

Plasma adsorption (PA) has been estab-

lished as a treatment for various LF condi-

tions, providing patients with additional

treatment options by temporarily and par-

tially replacing liver function 8-12. These

treatments can remove toxins, endotoxins,

and bilirubin metabolites from the blood, al-

lowing time for liver cell recovery and func-

232 Zhang et al.

Investigación Clínica 67(2): 2026

tion, or providing support while awaiting a

donor liver. PA is preferred because it avoids

plasma-dose limitations, plasma allergies,

and blood transfusion-related infections 8, 11.

This method introduces the patient’s blood

into the external pipeline, and the plasma

to be processed is separated by the plasma

component separator. The separated plasma

is then passed through a bilirubin adsorption

column to remove pathogenic substances

and returned to the patient without requir-

ing allogeneic plasma or albumin.

Plasorba BR-350 is a commonly used

bilirubin adsorption column capable of pro-

cessing large volumes of plasma to remove

bilirubin effectively 13, 14. PA mainly uses an

adsorption column to remove toxins from

patients’ plasma, including substances such

as albumin-bound bilirubin, thereby improv-

ing liver cells and liver function. According

to this principle, the role of the plasma bili-

rubin adsorption column is particularly criti-

cal 8-11. In lipoprotein (a) apheresis, different

treatment volumes affect the lipid removal

rate, as well as the removal of fibrinogen and

other macromolecules 15. Data are available

regarding the curative effect of the adsorp-

tion column material itself 13, 14, but there

remains a lack of data on whether different

adsorption capacities will produce different

curative effects. Although an adsorption ca-

pacity below 7 L can be treated using the

BR-350 adsorption column, current studies

mostly show that the treatment adsorption

time is 3-4 h (representing about 5-6 L) 13,

16-18. In patients on hemodialysis, the volume

of blood treated is associated with various

outcomes, such as hemodialysis efficacy and

intradialytic hypotension 19, 20. Hence, opti-

mizing benefits and limiting complications

is an important goal during blood purifica-

tion therapies.

Therefore, this study aimed to examine

how adsorption volume (5 L vs. 6 L) affects

clinical outcomes in patients with LF. The

results could help improve treatment and

nursing during PA.

MATERIALS AND METHODS

Study design and patients

This single-center retrospective study

included patients with LF who received PA

treatment at the First Affiliated Hospital of

Zhejiang University School of Medicine from

October 2020 to October 2022.

The inclusion criteria were 1) patients

diagnosed with LF according to the Chinese

Guidelines for Diagnosis and Treatment of

Liver Failure (2018) 21, 2) aged ≥18 years,

and 3) who underwent PA only. The exclusion

criteria were 1) patients with incomplete

clinical data, 2) patients with a malignant

tumor, 3) patients with severe infection,

such as pulmonary infection, or 4) patients

in the ICU.

This study was approved by the Medical

Ethics Committee of the First Affiliated Hos-

pital of Zhejiang University School of Medi-

cine. Patient informed consent was waived

due to the retrospective nature of the study.

All authors had full control of the data and

information for this study.

Data collection and definition

According to the infection depart-

ment’s artificial liver center standard op-

erating procedure and guidelines 21, an Ar-

tificial Liver Support System (ALSS) was

considered for patients with LF. Vascular

access was obtained with a double-lumen

hemodialysis catheter placed in the femoral

veins. Blood anticoagulation was managed

with unfractionated heparin. The anticoagu-

lant regimen consisted of an initial 2000 U

of heparin sodium, followed by maintenance

at 1000 U/h. The PA treatment device con-

sisted of a standard hemodialysis machine

with the appropriate tubing and plasma fil-

ter. The Plasorba BR-350 (B-Braun Carex)

was used as the bilirubin absorption column

during the study period, with a plasma pro-

cessing volume of 5L or 6L. The selection of

5L versus 6L plasma processing volume was

determined by the attending physician based

Plasma adsorption amounts in liver failure 233

Vol. 67(2): 230 - 240, 2026

on clinical judgment and the department’s

standard operating procedures during the

study period, rather than being predeter-

mined by patient anthropometric character-

istics such as height or body weight.

The patients’ identities were protected.

The demographic and clinical characteris-

tics were collected from the medical records,

including sex, age, height, weight, hyperten-

sion, allergies, diabetes, heart disease, kid-

ney disease, viral hepatitis, hepatocirrhosis,

hematocrit, and blood volume. The blood vol-

ume was estimated using 0.65×weight×(1-

hematocrit) 22.

Blood routine and coagulation function

indicators were collected, including white

blood cells (WBC), hemoglobin (HGB),

platelets (PLT), total bile acid (TBA), to-

tal bilirubin (TB), potassium (K+), sodium

(Na+), chlorine (Cl-), calcium (Ca2+), phos-

phorus (P), international normalized ratio

(INR), fibrinogen (Fib), activated partial

thromboplastin time (APTT), and prothrom-

bin time (PT). Percentage differences were

calculated as [(after treatment - before

treatment) / before treatment].

Outcomes

The outcomes of this study were the

length of hospital stay, liver transplant,

death, and improvement in disease-related

symptoms. Symptom improvement was de-

fined as 1) clinical symptoms such as fa-

tigue, poor appetite, abdominal distension,

and bleeding were significantly improved,

and hepatic encephalopathy disappeared; 2)

signs such as jaundice and ascites improved

significantly; and 3) liver function indices

improved significantly, such as TBil <5 the

upper limit of normal (ULN), PTA >40%, or

INR <1.5 21.

Statistical analysis

Continuous data were tested for nor-

mality using the Shapiro-Wilk test. Contin-

uous variables with a normal distribution

were expressed as means ± standard devia-

tions (SD) and analyzed using Student’s t-

test; otherwise, they were presented as me-

dians (interquartile ranges) and analyzed

using the Mann-Whitney U-test. Categorical

variables were presented as n (%) and ana-

lyzed using the chi-square test or Fisher’s

exact test. Data processing was performed

in Python, and data analysis was conducted

in SPSS 26.0 (IBM, Armonk, NY, USA). Two-

sided P-values <0.05 were considered statis-

tically significant.

RESULTS

During the study period, 230 plasma

adsorption (PA) treatments were performed

in 110 patients. Nine treatments were ex-

cluded for missing data, leaving 221 for

analysis of laboratory parameters (118 in

the 5L group and 103 in the 6L group). For

patient-level analyses of baseline character-

istics and clinical outcomes, 60 patients re-

ceived 5L PA and 50 received 6L PA. Patients

in the 5L group were significantly taller than

those in the 6L group (166.14±7.18 cm vs.

163.13±7.24 cm, p=0.031), but the estimat-

ed systemic blood volume (0.65×weight×(1-

hematocrit)) did not differ significantly

between groups (2732.29±453.71 mL vs.

2683.34±508.21 mL, p=0.595). Other

baseline characteristics, including the prev-

alence of viral hepatitis, hypertension, dia-

betes, and renal disease, were comparable

between groups (Table 1).

The majority of patients were male

(70.9%), and males had a higher mean system-

ic blood volume than females (2838±452 mL

vs. 2395±387 mL). The mean age of the entire

cohort was 55.4±13.8 years. Patients in the 5L

group were significantly taller than those in the

6L group (p=0.031). Viral hepatitis was the

most common underlying disease (30%). No

significant differences were observed between

groups in the prevalence of hypertension,

diabetes, heart disease, or kidney disease (all

p>0.05) (Table 1). Baseline laboratory param-

eters, including total bile acid and total biliru-

bin levels, were comparable between the two

groups prior to treatment (all p>0.05).

234 Zhang et al.

Investigación Clínica 67(2): 2026

In both groups, PA treatment signifi-

cantly increased white blood cell counts,

INR, APTT, and PT, while decreasing hemo-

globin, total bilirubin, total bile acids, and

fibrinogen (all p<0.05) (Supplementary

Table 1). Notably, platelet levels decreased

significantly after 6L PA (p=0.033), whereas

no significant reduction was observed after

5L PA (p=0.116).

Post-treatment comparisons between

groups showed significantly lower white

blood cell counts in the 6L group than in

the 5L group (p=0.003). No significant

between-group differences were observed

in other post-treatment laboratory param-

eters, including hemoglobin, platelets, bili-

rubin, coagulation indices, or electrolytes

(Table 2).

At the patient level, no significant dif-

ferences were observed between the 5L and

6L groups in length of hospital stay, liver

transplantation rates, in-hospital mortality,

or improvement in disease-related symp-

toms (all p>0.05) (Table 3). Although the

5L group had a numerically longer mean

hospital stay and higher transplantation and

mortality rates, and the 6L group showed a

slightly higher improvement rate, none of

these differences reached statistical signifi-

cance.

DISCUSSION

The 5L and 6L columns yield similar

outcomes in terms of hospital stay dura-

tion, liver transplantation, mortality, and

symptom improvement. The 5L column can

reduce platelet destruction, shorten treat-

ment time, and reduce the occurrence of

complications.

In patients with LF, high bilirubin levels

can be fatal in the short term 13, 14. Low bili-

rubin levels can promote hepatocyte regen-

eration, whereas high bile acid levels can in-

duce hepatocyte apoptosis and necrosis and

delay regeneration 3, 23, 24. Excessive bilirubin

Table 1. Baseline characteristics.

Variable 5L group (n=60) 6L group (n=50) p

Sex, n (%)

0.065 Female 13 (21.7%) 19 (38%)

Male 47 (78.3%) 31 (62%)

Age, year, mean ± SD 54.00±12.53 57.17±15.20 0.233

Height, cm, mean ± SD 166.14±7.18 163.13±7.24 0.031

Weight, kg, mean ± SD 61.57±10.24 60.41±2.48 0.592

Hypertension, n (%) 12 (20%) 9 (18%) 0.793

Allergy, n (%) 1 (1.7%) 2 (4%) 0.459

Diabetes, n (%) 7 (11.7%) 6 (12%) 0.957

Heart disease, n (%) 1 (1.7%) 1 (2%) 0.898

Kidney disease, n (%) 4 (6.7%) 1 (2%) 0.224

Virus hepatitis, n (%) 19 (31.7%) 14 (28%) 0.679

Hepatocirrhosis, n (%) 0 1 (2%) 0.275

Hematocrit, median (interquartile range) 31.44 (5.74) 30.99 (7.49) 0.730

Blood volume, median (interquartile range) 2732.29 (453.71) 2683.34 (508.21) 0.595

Continuous variables were analyzed using Student’s t-test for normally distributed data (expressed as mean ± SD)

and the Mann-Whitney U-test for non-normally distributed data (expressed as median with interquartile range).

Categorical variables were analyzed using the chi-square test or Fisher’s exact test.

Plasma adsorption amounts in liver failure 235

Vol. 67(2): 230 - 240, 2026

itself does not cause multiple organ failure,

but in patients with LF it has neurotoxic and

encephalopathic effects. Therefore, remov-

ing bilirubin and bile acids seems a reason-

able therapeutic goal. ALSS can help remove

toxic metabolites in patients with LF, which

is beneficial for liver cell regeneration and

functional recovery, buys time for liver trans-

plantation, and can even allow some patients

to avoid liver transplantation 8, 10, 25. PA can

selectively adsorb lipid-soluble substances

such as bilirubin, aromatic amino acids,

and other toxic metabolites that are tight-

ly bound to proteins. Although many stud-

ies have examined the efficacy of ALSS 3, 8,

10,13,26,27, there are few data on different PA

amounts and even fewer studies in large pop-

ulations. It is unclear whether the amount of

adsorption in the clinic will have the same

effect across patients with LF. In the pres-

ent study, bilirubin decreased in both groups

after treatment, which is the goal of treat-

ment. WBCs increased, probably due to an

immune insult from the treatment. Fibrino-

Table 2. Laboratory indices after treatment.

Variable 5L group (n=118) 6L group (n=103) p

WBC, x109/L 11.57±10.29 8.29±3.84 0.003

HGB, g/L 107.61±22.76 102.42±26.12 0.116

PLT, x109/L 166.43±88.66 155.70±84.15 0.359

TBA, µmol/L 170.04±115.27 152.53±104.54 0.241

TB, µmol/L 251.16±107.54 238.27±106.26 0.372

Na, mmol/L 136.81±4.6 137.79±3.25 0.068

Cl, mmol/L 101.99±4.55 102.01±3.97 0.975

Ca, mmol/L 2.13±0.12 2.15±0.13 0.493

P, mmol/L 0.98±0.24 0.92±0.26 0.125

INR 1.80±3.55 1.44±0.38 0.301

Fib, g/L 1.80±0.68 1.92±0.74 0.224

APTT, s 45.69±19.07 42.68±12.76 0.167

PT, s 17.00±4.19 16.53±4.19 0.413

White blood cells (WBC), hemoglobin (HGB), platelets (PLT), total bile acid (TBA), total bilirubin (TB), sodium

(Na+), chlorine (Cl-), calcium (Ca2+), phosphorus (P), international normalized ratio (INR), fibrinogen (Fib),

activated partial thromboplastin time (APTT), and prothrombin time (PT). Between-group comparisons of post-

treatment laboratory parameters were performed using Student’s t-test for normally distributed continuous vari-

ables, with data presented as mean ± standard deviation.

Table 3. Clinical outcomes.

Variable 5L group (n=60) 6L group (n=50) p

Length of stay (days) 23.7±19.86 19.4±8.78 0.135

Liver transplant 6 (10%) 3 (6%) 0.451

In-hospital mortality 8 (13.3%) 4 (8%) 0.376

Good prognosis 45 (75%) 42 (85%) 0.245

Length of hospital stay was analyzed using Student’s t-test, and categorical outcomes (liver transplant, in-hospital

mortality, and good prognosis) were analyzed using the chi-square test or Fisher’s exact test. All data are presented

as mean ± SD or n (%).

236 Zhang et al.

Investigación Clínica 67(2): 2026

gen decreased, and PT and APPT increased,

suggesting reduced coagulation function,

probably due to adsorption of coagulation

factors by the column. HGB also decreased.

The PA treatment mode is a mature,

classic method that addresses the issue of

scarce plasma supply. The 5-L and 6-L ad-

sorption capacities are routine choices in

adults. This study showed that 1) the 5-L and

6-L adsorption doses could be considered ef-

fective strategies for treating patients with

LF, with no differences in treatment out-

comes; 2) there might be a risk of thrombo-

cytopenia after treatment with a PA volume

of 6 L, but not with 5 L; and 3) since the

treatment time is shorter with 5 L, the 5-L

volume could be associated with lower com-

plication rates.

BR-350 is an anion resin plasma adsorp-

tion column with styrene-divinylbenzene as

the main material. The effective use of BR-

350 in LF dates back more than 30 years8,

10,25. Previous studies have reported that

the amount of PA in LF treatment ranges

from 2 to 7 L, and the clearance rate of BR-

350 for bilirubin decreases with increasing

treatment volume and eventually tends to

saturate 13. As shown in the present study,

there were no significant differences in post-

treatment bilirubin and TBA between 5 and

6 L. Some researchers have suggested that

a longer PA treatment time can lead to a

higher incidence of complications 28. There-

fore, in the case of the same treatment ef-

fect, a 5L treatment capacity seems to be a

better choice because of the shorter treat-

ment time. Nursing care for ALSS treatment

needs to be refined and individualized, and

timely analysis of the cause of alarms in the

treatment system and handling of emergen-

cies are required to ensure patient safety

and the smooth progress of treatment.

The most critical safety distinction be-

tween the two treatment volumes lies in their

differential effects on hematological param-

eters. While both 5L and 6L PA effectively re-

duced bilirubin and bile acids, the 6L volume

was associated with a significant decrease in

platelet counts (p=0.033), whereas the 5L

volume preserved platelet levels (p=0.116).

This finding carries substantial clinical sig-

nificance for patients with liver failure, who

already exhibit compromised hemostasis

due to impaired synthesis of coagulation fac-

tors and often baseline thrombocytopenia 29.

Further platelet reduction in this vulnerable

population increases the risk of spontaneous

bleeding and procedure-related hemorrhage

and may necessitate platelet transfusions,

thereby increasing treatment costs and

risks30,31. Additionally, the 6L group demon-

strated significantly lower post-treatment

white blood cell counts compared to the 5L

group (p=0.003). Although we did not ob-

serve a statistically significant increase in in-

fection rates in the 6L group during the study

period, leukopenia theoretically elevates in-

fection risk, which is particularly concern-

ing in patients with liver failure who exhibit

immune dysfunction. The combination of

thrombocytopenia and leukopenia suggests

that the 6L volume may impose greater he-

matological stress or more pronounced acti-

vation of cellular adhesion to the adsorption

column and extracorporeal circuit. Patients

with LF are at risk of thrombocytopenia due

to factors such as decreased thrombopoi-

etin synthesis from massive necrosis of liver

cells32,33. Blood purification treatments such

as bilirubin adsorption will cause increased

platelet consumption, and at the same time,

there is an increased risk of HIT due to hep-

arin anticoagulation. A researcher found

that the proportion of patients with ampu-

tation or death due to HIT was as high as

20%-30% 33. At the same time, an elevated

time-to-risk of transient thrombocytopenia

associated with separation membranes was

associated 31. This study found a statistically

significant decrease in platelet counts with

6-L PA, suggesting that 5-L PA may be safer.

A previous study of lipoprotein(a) apheresis

showed that larger treatment volumes were

associated with larger decreases in the lev-

els of fibrinogen and other blood macromol-

ecules 15, but no significant differences were

Plasma adsorption amounts in liver failure 237

Vol. 67(2): 230 - 240, 2026

observed in the present study. The 6L group

had lower WBC levels than the 5L group af-

ter treatment. Although our study did not

find a significant increase in infection rates

in the 6 L group, we acknowledge that leu-

kopenia may theoretically elevate infection

risk 34. Future studies with larger cohorts

and longer follow-up may further elucidate

this relationship. Nevertheless, differences

could be observed in larger cohorts or with

longer follow-up.

We acknowledge that the 5L group had

a significantly greater mean height than the

6L group. Although height can correlate

with blood volume, we believe this difference

is unlikely to have influenced the choice of

adsorption volume or the study outcomes

for several reasons. First, the estimated sys-

temic blood volume, calculated using the for-

mula 0.65×weight×(1-hematocrit), showed

no significant difference between groups

(p=0.595), suggesting that the height dis-

parity did not translate into clinically relevant

differences in total circulating volume. Sec-

ond, in clinical practice, the decision to use

5L versus 6L adsorption is typically based on

the severity of liver failure, baseline bilirubin

levels, and physician preference rather than

patient height. Nevertheless, we recognize

this baseline imbalance as a limitation of our

retrospective design, and we cannot entirely

exclude the possibility of unmeasured con-

founding factors that may influence both pa-

tient selection and volume determination.

This study had limitations. It was a

single-center study with a small sample size.

The retrospective design limited the data to

what was available in the charts. The 5-L and

6-L capacities are the most common at the

authors’ center, but future studies should

also examine other capacities.

In conclusion, PA therapy can remove a

large amount of bilirubin and also reuse the

patient’s plasma and albumin to reduce al-

lergic reactions. Treatment with a 5-L plasma

adsorption capacity yields outcomes similar

to those of the 6-L treatment for length of

stay, liver transplantation, in-hospital mor-

tality, and prognosis. However, given smaller

post-treatment platelet changes and a short-

er treatment duration, the 5-L treatment

volume might be more appropriate than the

6-L volume.

Acknowledgements

The authors would like to thank the

State Key Laboratory for Diagnosis and

Treatment of Infectious Diseases, The First

Affiliated Hospital, Zhejiang University

School of Medicine, for providing the re-

search platform and support. We are also

grateful to the medical and nursing staff

of the Artificial Liver Treatment Center for

their clinical assistance and patient care.

Finally, we acknowledge all patients in-

volved in this study.

Funding

This research received no specific grant

from any funding agency in the public, com-

mercial, or not-for-profit sectors.

ORCID ID of the authors

• Xin Zhang (XZ):

0009-0000-6607-0499

• Zhuoyao Zhang (ZYZ):

0009-0004-3294-4003

• Hui Chen (HC):

0009-0008-7594-2701

• Huafen Zhang (HFZ):

0000-0002-5371-7895

Author’s contributions

XZ: Conceptualization, Methodology,

Investigation, Formal Analysis, Writing –

Original Draft; ZYZ: Methodology, Investi-

gation, Formal Analysis; HC: Methodology,

Investigation, Formal Analysis; HFZ: Concep-

tualization, Writing – Original Draft, Writing

– Review & Editing, Supervision, Project Ad-

ministration. All authors contributed to re-

sources, reviewed and edited the manuscript,

and approved the final version for submission.

238 Zhang et al.

Investigación Clínica 67(2): 2026

Conflict of interest

The authors declare that they have no

competing interests.

Ethics approval and consent to participate

This work has been carried out in accor-

dance with the Declaration of Helsinki (2000)

of the World Medical Association. This study

was approved by the Ethic Committee of the

First Affiliated Hospital, College of Medi-

cine, Zhejiang University (IIT20230143A).

The requirement for informed consent from

the patients was waived due to the retrospec-

tive nature of the study. All authors had full

control of the data and information regard-

ing this study.

Consent for publication

Not applicable.

Availability of data and materials

All data generated or analyzed during

this study are included in this article and

supplementary information files.

REFERENCES

1. Moreau R, Jalan R, Gines P, Pavesi M, An-

geli P, Cordoba J, et al. Acute-on-chronic

liver failure is a distinct syndrome that

develops in patients with acute decom-

pensation of cirrhosis. Gastroenterology.

2013;144(7):1426-1437, 1437 e1421-

1429. https://doi.org/10.1053/j.gas-

tro.2013.02.042.

2. Angeli P, Rodríguez E, Piano S, Ariza X,

Morando F, Solà E, et al. Acute kidney inju-

ry and acute-on-chronic liver failure classifi-

cations in prognosis assessment of patients

with acute decompensation of cirrhosis.

Gut. 2015;64(10):1616-1622. https://doi.

org/10.1136/gutjnl-2014-307526.

3. Lee JY, Kim SB, Chang JW, Park SK, Kwon

SW, Song KW, et al. Comparison of the molec-

ular adsorbent recirculating system and plas-

mapheresis for patients with graft dysfunc-

tion after liver transplantation. Transplant

Proc. 2010;42(7):2625-2630. https://doi.

org/10.1016/j.transproceed.2010.04.070.

4. European Association for the Study of

the Liver, Electronic address eee, Clini-

cal practice guidelines panel, Wendon J,

Panel members, Cordoba J, et al. EASL

Clinical Practical Guidelines on the man-

agement of acute (fulminant) liver failure.

J Hepatol. 2017;66(5):1047-1081. https://

doi.org/10.1016/j.jhep.2016.12.003.

5. Alarabi AA, Wikstrom B, Loof L, Dan-

ielson BG. Treatment of pruritus in

cholestatic jaundice by bilirubin- and

bile acid-adsorbing resin column plas-

ma perfusion. Scand J Gastroenterol.

1992;27(3):223-226. https://doi.org/10.3

109/00365529208999953.

6. Mandiga P, Kommu S, Foris LA, Bollu PC.

Hepatic Encephalopathy. In: StatPearls.

Treasure Island (FL); StatPearls Publish-

ing; 2026. Available from: https://www.

ncbi.nlm.nih.gov/books/NBK430869/

7. Francoz C, Durand F, Kahn JA, Genyk YS,

Nadim MK. Hepatorenal Syndrome. Clin

J Am Soc Nephrol. 2019;14(5):774-781.

https://doi.org/10.2215/CJN.12451018.

8. Viggiano D, de Pascale E, Marinelli G,

Pluvio C. A comparison among three dif-

ferent apheretic techniques for treat-

ment of hyperbilirubinemia. J Artif Or-

gans. 2018;21(1):110-116. https://doi.

org/10.1007/s10047-017-0986-1.

9. Fuhrmann V, Horvatits T, Drolz A, Rut-

ter K. [Extracorporeal therapy of pa-

tients with liver disease in the intensive

care unit]. Med Klin Intensivmed Not-

fmed. 2014;109(4):246-251. https://doi.

org/10.1007/s00063-013-0321-4.

10. Saliba F, Bañares R, Larsen FS, Wilmer

A, Parés A, Mitzner S, et al. Artificial

liver support in patients with liver fail-

ure: a modified DELPHI consensus of in-

ternational experts. Intensive Care Med.

2022;48(10):1352-1367. https://doi.org/1

0.1007/s00134-022-06802-1.

11. Sun Y, Yu LX, Liu YH, Wang B, Lu W.

[Bilirubin adsorption therapy for two in-

fants with liver failure]. Zhonghua Er Ke

Plasma adsorption amounts in liver failure 239

Vol. 67(2): 230 - 240, 2026

Za Zhi. 2020;58(11):933-934. https://doi.

org/10.3760/cma.j.cn112140-2020041

1-00376.

12. Tsipotis E, Shuja A, Jaber BL. Albu-

min Dialysis for Liver Failure: A Sys-

tematic Review. Adv Chronic Kidney

Dis. 2015;22(5):382-390. https://doi.

org/10.1053/j.ackd.2015.05.004.

13. Adani GL, Lorenzin D, Currò G, Sainz-

Barriga M, Comuzzi C, Bresadola V, et

al. Selective bilirubin removal by plasma

treatment with Plasorba BR-350 for early

cholestatic graft dysfunction. Transplant

Proc. 2007;39(6):1904-1906. https://doi.

org/10.1016/j.transproceed.2007.05.010.

14. Geiger H, Klepper J, Lux P, Heidland

A. Biochemical assessment and clinical

evaluation of a bilirubin adsorbent col-

umn (BR-350) in critically ill patients with

intractable jaundice. Int J Artif Organs.

1992;15(1):35-39. PMID: 1551726.

15. Borberg H. Comparison of different

Lp (a) elimination techniques: a retro-

spective evaluation. Transfus Apher Sci.

2009;41(1):61-65. https://doi.org/10.101

6/j.transci.2009.05.014.

16. Ihara H, Shino Y, Hashizume N, Aoki T,

Suzuki Y, Igarasi Y, et al. Decline in plas-

ma retinol in unconjugated hyperbilirubi-

nemia treated with bilirubin adsorption

using an anion-exchange resin. J Nutr Sci

Vitaminol (Tokyo). 1998;44(2):329-336.

https://doi.org/10.3177/jnsv.44.329.

17. Ryan CJ, Anilkumar T, Ben-Hamida AJ,

Khorsandi SE, Aslam M, Pusey CD, et

al. Multisorbent plasma perfusion in ful-

minant hepatic failure: effects of dura-

tion and frequency of treatment in rats

with grade III hepatic coma. Artif Organs.

2001;25(2):109-118. https://doi.org/10.1046/

j.1525-1594.2001.025002109.x.

18. Mertens PR, Schönfelder T, Handt S, Kier-

dorf H, Marschall H, Busch N, et al. Long-

term extracorporeal bilirubin elimination:

A case report on cascade resin plasmaper-

fusion. Blood Purif. 1998;16(6):341-348.

https://doi.org/10.1159/000014354.

19. Thijssen S, Kappel F, Kotanko P. Absolute

blood volume in hemodialysis patients:

why is it relevant, and how to measure it?

Blood Purif. 2013;35(1-3):63-71. https://

doi.org/10.1159/000345484.

20. Nafisi VR, Eghbal M. Optimized Blood

Volume Monitoring during Hemodialy-

sis Procedure based on Ultrasonic Speed

Measurement. J Biomed Phys Eng.

2019;9(3):373-380. https://doi.org/10.31

661/jbpe.v9i3Jun.675.

21. Liver Failure and Artificial Liver Group,

Chinese Society of Infectious Diseas-

es, Chinese Medical Association, Se-

vere Liver Disease and Artificial Liver

Group, Chinese Society of Hepatology,

Chinese Medical Association. [Guide-

line for diagnosis and treatment of liver

failure (2018)]. Zhonghua Gan Zang

Bing Za Zhi. 2019;27(1):18-26. https://

doi.org/10.3760/cma.j.issn.1007-341

8.2019.01.006.

22. Kaplan AA. A simple and accurate method

for prescribing plasma exchange. ASAIO

Trans. 1990;36(3):M597-599. PMID: 2252

761.

23. Liang C, Takahashi K, Furuya K,

Oda T, Ohkohchi N. Platelets Stimu-

late Liver Regeneration in a Rat Model

of Partial Liver Transplantation. Liver

Transpl. 2021;27(5):719-734. https://doi.

org/10.1002/lt.25962.

24. Chamuleau RA, Aronson DC, Frederiks

WM, Bosman DK, Smit JJ, Maas MA, et

al. Liver regeneration after partial hepa-

tectomy in rats with defective bilirubin

conjugation or biliary excretion. Dig Dis

Sci. 1991;36(4):510-512. https://doi.org/

10.1007/BF01298884.

25. Larsen FS. Artificial liver support in acute

and acute-on-chronic liver failure. Curr

Opin Crit Care. 2019;25(2):187-191.

https://doi.org/10.1097/MCC.0000000

000000584.

26. Che XQ, Li ZQ, Chen Z, Guo D, Jia QY,

Jiang SC, et al. Plasma exchange com-

bining with plasma bilirubin adsorption

effectively removes toxic substances and

improves liver functions of hepatic fail-

ure patients. Eur Rev Med Pharmacol

Sci. 2018;22(4):1118-1125. https://doi.

org/10.26355/eurrev_201802_14400.

240 Zhang et al.

Investigación Clínica 67(2): 2026

27. Senf R, Klingel R, Kurz S, Tullius S, Sau-

er I, Frei U, et al. Bilirubin-adsorption in

23 critically ill patients with liver failure.

Int J Artif Organs. 2004;27(8):717-722.

https://doi.org/10.1177/0391398804027

00810.

28. Schwanke AA, Danski MTR, Pontes L,

Kusma SZ, Lind J. Central venous cath-

eter for hemodialysis: incidence of infec-

tion and risk factors. Rev Bras Enferm.

2018;71(3):1115-1121. https://doi.org/

10.1590/0034-7167-2017-0047.

29. Daugirdas JT, Bernardo AA. Hemodialy-

sis effect on platelet count and function

and hemodialysis-associated thrombocy-

topenia. Kidney Int. 2012;82(2):147-157.

https://doi.org/10.1038/ki.2012.130.

30. Doi Y, Koga K, Sugioka S, Inoue Y, Ari-

sato T, Nishioka K, et al. Heparin-induced

thrombocytopenia among incident hemo-

dialysis patients anticoagulated with low

molecular weight heparin: A single-cen-

ter retrospective study. Nefrologia (Engl

Ed). 2021;41(3):356-358. https://doi.

org/10.1016/j.nefroe.2020.05.007.

31. Hakim RM, Schafer AI. Hemodialysis-

associated platelet activation and throm-

bocytopenia. Am J Med. 1985;78(4):575-

580. https://doi.org/10.1016/0002-9343

(85)90398-5.

32. Giannini EG, Peck-Radosavljevic M.

Platelet Dysfunction: Status of Thrombo-

poietin in Thrombocytopenia Associated

with Chronic Liver Failure. Semin Thromb

Hemost. 2015;41(5):455-461. https://doi.

org/10.1055/s-0035-1550432.

33. Fathi M. Heparin-induced thrombocyto-

penia (HIT): Identification and treatment

pathways. Glob Cardiol Sci Pract. 2018;

2018(2):15. https://doi.org/10.21542/

gcsp.2018.15.

34. Khan MTA, Patnaik R, Huang JY, Campi

HD, Montorfano L, De Stefano F, et al.

Leukopenia is an independent risk factor

for early postoperative complications fol-

lowing incision and drainage of anorectal

abscess. Colorectal Dis. 2023. 25(4):717-

727. https://doi.org/10.1111/codi.16447.