Acute-On-Chronic Liver Failure, Sepsis
Conditions
Brief summary
This study aims to evaluate the efficacy and safety of the double plasma cytokine adsorption system with sequential low-dose plasma exchange (DPCAS+LPE) in patients with acute-on-chronic liver failure (ACLF) complicated by sepsis. The focus is on assessing the impact of the cytokine adsorption column(CA280,Jafron Biomedical Co., Ltd., Zhuhai, China) on survival rates, inflammation markers, and organ function to determine its potential value in clinical practice. The primary research questions are: (1) Does DPCAS+LPE artificial liver therapy improve the 4-week mortality rate in ACLF patients with sepsis? (2) Does it improve the 12-week mortality rate in these patients? Additionally, the study examines the effects of this therapy on APACHE II scores, SOFA scores, vasoactive-inotropic score, MELD scores, and COSSH-ACLF II scores, as well as the cytokine adsorption efficiency of the CA280. Patients were randomly assigned to either the DPCAS+LPE group or the plasma exchange(PE) group. All patients received artificial liver therapy every other day, for a total of two sessions. Follow-up assessments were conducted before and after each therapy session, as well as at 1, 2, 3, 4, and 12 weeks.
Interventions
DEVICEdouble plasma cytokine adsorption system with sequential low-dose plasma exchange
Both groups received comprehensive medical treatment, including antiviral therapy, anti-infection treatment, supportive care, symptomatic treatment, and prevention of complications. All patients will initiate ALSS within 48 hours of enrollment, with treatment administered every other day, for a total of three sessions. The experimental group： The first two sessions consisted of a double plasma cytokine adsorption system with sequential low-dose plasma exchange (DPCAS+LPE). This involved using a cytokine adsorption column (CA280,Jafron Biomedical Co., Ltd., Zhuhai, China) and a bilirubin adsorption device (BS330,Jafron Biomedical Co., Ltd., Zhuhai, China) on the same treatment circuit. DPCAS treatment was performed first, with an adsorption volume of 4500ml to 5000ml over 2 to 3 hours, followed by plasma exchange (PE), with 1000ml of plasma and 500ml of 4% albumin being infused. The third treatment was plasma exchange, with the same dosing as in the control group.
OTHERplasma exchange
Based on comprehensive medical treatment, the control group received plasma exchange(PE) treatment, where whole blood was processed through a plasma separator (MICROPLAS MPS 07, BELLCO S.R.L., Italy), with a portion of the plasma discarded and replaced with 1000ml of plasma and 500ml of 4% albumin.Three sessions of plasma exchange (PE) performed every other day.
Sponsors
Third Affiliated Hospital, Sun Yat-Sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 and 70 years with a background of chronic liver disease, regardless of the presence of cirrhosis. 2. Total bilirubin (TBIL) \> 12 mg/dL. 3. International normalized ratio (INR) ≥ 1.5. 4. Meeting the diagnostic criteria for sepsis: confirmed or suspected infection, with a sequential organ failure assessment (SOFA) score increase of ≥ 2 points. (5) High inflammatory status: IL-6 \> 80 pg/ml. (6) Diagnosis of sepsis within the past 72 hours.
Exclusion criteria
1. Inherited metabolic liver disease (including Wilson's disease, hereditary hemochromatosis, and alpha-1 antitrypsin deficiency). 2. Patients with hepatocellular carcinoma or other malignancies. 3. Pregnant or breastfeeding women. 4. Patients with human immunodeficiency virus (HIV) infection or other immunodeficiency diseases (including active hematological malignancies, congenital immunodeficiency syndromes, or those currently receiving high-dose systemic immunosuppressive therapy). 5. Unstable phase of cerebrovascular events. 6. History of organ transplantation. 7. Patients with irreversible or terminal extrahepatic organ failure that precludes safe extracorporeal circulation or confounds the intervention: ①Terminal chronic obstructive pulmonary disease, terminal cor pulmonale, brain death, or persistent vegetative state, or Grade IV hepatic encephalopathy. ②Requirement for renal replacement therapy (RRT) at the time of screening/enrollment. ③Despite adequate fluid resuscitation, vasopressors, and steroid treatment, unable to maintain mean arterial pressure above 65 mmHg. 8. Platelet count \< 50×10E9/L, severe coagulation disorders (INR\>3.5), or active bleeding. 9. Known allergies to extracorporeal circulation, hemoperfusion, or other severe allergic history. 10. Refusal by the patient or their legally authorized representative (LAR) to participate in the study, or sign the informed consent form. 11. Inability to return for regular follow-up visits as planned in the study. 12. Other conditions that, in the judgment of the researchers, make the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality rate | 4 weeks | 4-week mortality rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality rate | 12 weeks | 12-week Mortality rate |
| Changes in Acute Physiology and Chronic Health Evaluation II score from baseline | 1, 2, 3, and 4 weeks | The theoretical maximum value of Acute Physiology and Chronic Health Evaluation II score（APACHE II score） was 71 points. The higher the score, the higher the risk of death. Patients with more than 15 points were classified as severe, and patients with less than 15 points were classified as non-severe. |
| Changes in sequential organ failure assessment score from baseline | 1, 2, 3, and 4 weeks | The theoretical value range of sequential organ failure assessment（SOFA） score is 6-24. The higher the score, the worse the prognosis. |
| Changes in vasoactive-inotropic score from baseline | 1, 2, 3, and 4 weeks | Vasoactive-Inotropic Score ( VIS ) evaluates cardiac function and the intensity of vasoactive drug therapy in critically ill patients by quantifying the dose of vasoactive and inotropic drugs received by patients. VIS has no special value range. The higher the score, the higher the patient 's dependence on vasoactive drugs. |
| Changes in Model for End-Stage Liver Disease score from baseline | 1, 2, 3, and 4 weeks | MELD score is now widely used in the prioritization of liver transplantation candidates in many countries. The score range is usually between 6 ( low risk ) and 40 ( high risk ). |
| Changes in COSSH-ACLF II score from baseline | 1, 2, 3, and 4 weeks | COSSH-ACLF II is a prognostic scoring system for hepatitis B virus -related acute-on-chronic liver failure（HBV-ACLF）. COSSH-ACLF IIs can significantly divide ACLF patients into three risk groups based on two cutoff values of 7.4 and 8.4 : low-risk group ( \< 7.4 points ), medium-risk group ( 7.4-8.4 points ) and high-risk group ( ≥ 8.4 points ). |
| Adsorption rates of various cytokines | Day1 | Adsorption rates of various cytokines (including pro-inflammatory and anti-inflammatory cytokines) after each treatment |
| Adsorption rates of lactate | Day1 | Adsorption rates of lactate after each treatment |
Countries
China
Contacts
CONTACTLiang Peng, Doctor
CONTACTWenxiong Xu, Doctor
PRINCIPAL_INVESTIGATORLiang Peng, Doctor
Third Affiliated Hospital, Sun Yat-Sen University
Outcome results
None listed