Clinical Observation of CABA System in the Treatment of End-stage Liver Disease With Inflammation

Clinical Observation of New Artificial Liver CABA System (BS330+CA280) in the Treatment of End-stage Liver Disease With Inflammation

End-stage liver disease (ESLD) refers to the late stage of liver disease caused by various chronic liver damage. ESLD is an important cause of global incidence rate and mortality, which has a significant impact on the health care system.

ESLD is associated with various types of immune dysfunction. The artificial liver support system (ALSS) is an extracorporeal support system that temporarily and partially replaces the partial function of the liver. Its treatment mechanism is to remove all kinds of harmful substances, supplement essential substances, improve the internal environment, create conditions for hepatocyte regeneration and liver function recovery, or use it as a symptomatic support treatment method during the perioperative period of liver transplantation. In this study, we plan to use BS330 for plasma bilirubin adsorption. On this basis, we will add a CA280 cytokine adsorption column to establish a new artificial liver combination model CABA for the immune inflammatory damage mechanism of liver failure.

Study Overview

• Status: Recruiting
• Conditions: To Evaluate the Clinical Efficacy and Safety of the New ALSS
• Intervention / Treatment: Device: New artificial liver CABA system (BS330+CA280) +PE

Detailed Description

End-stage liver disease (ESLD) refers to the late stage of liver disease caused by various chronic liver damage. Its main feature is that the liver function cannot meet the physiological needs of the human body. Its scope includes the end stage of various chronic liver diseases, including chronic plus acute liver failure (ACLF), acute decompensation of cirrhosis (ADC), chronic liver failure (CLF) and hepatocellular carcinoma. ESLD is an important cause of global incidence rate and mortality, which has a significant impact on the health care system.

ESLD is associated with various types of immune dysfunction. The symptoms of these immune dysfunction are called cirrhosis-related immune dysfunction (CAID), characterized by immune deficiency and systemic inflammation caused by the continuous and inappropriate activation of immune cells. In compensated cirrhosis, even without intestinal bacterial translocation, the damage-related molecular patterns (DAMPs) released by necrotic hepatocytes can activate the immune system and cause systemic inflammation. During the decompensation period, the bacterial products produced by intestinal bacterial translocation enhance immune activation and increase the expression of pro-inflammatory cytokines and immune cell activation antigens in the circulation. Cytokines are the key components of the immune system, with a variety of characteristics and biological functions. Systemic inflammation associated with CAID is associated with increased circulating levels of pro-inflammatory cytokines such as interleukin (IL) - 6. Studies have shown that there is a relationship between the severity of immune disorders and the prognosis of liver cirrhosis. The levels of IL-6, IL-10 and IL-17 are increased in liver cirrhosis.

The artificial liver support system (ALSS) is an extracorporeal support system that temporarily and partially replaces the partial function of the liver. Its treatment mechanism is to remove all kinds of harmful substances, supplement essential substances, improve the internal environment, create conditions for hepatocyte regeneration and liver function recovery, or use it as a symptomatic support treatment method during the perioperative period of liver transplantation. Plasma bilirubin adsorption is the specific adsorption of bilirubin through anion resin adsorption column, which can effectively reduce the level of bilirubin and bile acid, thus improving the internal environment of the machine and helping the further repair of damaged liver cells. Cytokine adsorption is designed to reduce the level of cytokines represented by IL-6 through the cytokine adsorption column. In clinical practice, it is mainly used to reduce the level of circulating pro-inflammatory cytokines and early harmful effects in the first few hours and days of treatment of infectious shock, so as to improve the treatment effect of patients. In this study, we plan to use BS330 for plasma bilirubin adsorption. On this basis, we will add a CA280 cytokine adsorption column to establish a new artificial liver combination model CABA for the immune inflammatory damage mechanism of liver failure. This treatment model can not only absorb bilirubin, but also effectively remove more inflammatory factors. In this study, patients with end-stage liver disease and inflammatory status will be selected as the observation object, and the new CABA combination will be used for treatment, and the clinical effectiveness and safety of this treatment mode will be evaluated, aiming to provide evidence-based medical evidence for the clinical application and promotion of this treatment mode.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital
      • Contact: Yang Zhongyuan, MD/PhD; Phone Number: 0086 2783662391; Email: 1049446560@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

① Age 18-70;

② Patients with end-stage liver disease, including patients with acute decompensation of cirrhosis, chronic liver failure and patients with chronic and acute liver failure in Child-Pugh grade B-C;

A. Acute decompensation of liver cirrhosis:

1. ALB<35 g/L; A / G <1.0;
2. TBIL> 120 μ mol / L;
3. ALT> 1 × ULN and/or AST>1 × ULN;
4. PTA <60%
5. Ascites or hepatic encephalopathy or bleeding from esophageal varices;

B. Chronic liver failure:

1. The basis of chronic liver disease: decompensated cirrhosis;
2. Time of onset: unlimited;
3. Hepatic encephalopathy: with or without;
4. Coagulation: PTA ≤ 40% or INR ≥ 1.5;
5. Jaundice>171.1umol/L;

C. Chronic plus acute liver failure:

1. Chronic liver disease is based on: chronic hepatitis or decompensated cirrhosis;
2. Time of onset:<4 weeks;
3. Hepatic encephalopathy: with or without;
4. Coagulation: PTA ≤ 40% or INR ≥ 1.5;

5. Jaundice: TBIL ≥ 171 μ Mol/L or daily increase ≥ 17.1 μ mol/L

   ③ Inflammation status: the following 4 items meet any 2 items

   1. PCT≥0.50 μ g/L
   2. CRP≥40 mg/L
   3. IL-6 > 5 × ULN

   4. IL-8 > 5 × ULN

      ④ Understand and voluntarily sign the informed consent form approved by the Ethics Committee.

      Exclusion Criteria:

      • Patients with liver malignant tumor and other tumors;

        • People with HIV infection or other immunodeficiency diseases;

          • Pregnant or lactating women;

            • Patients with autoimmune disease, unstable stage of infarction caused by cardio-cerebrovascular accident, history of organ transplantation and other organ dysfunction or failure; ⑤ Patients with other serious complications (such as active bleeding, diffuse intravascular coagulation); ⑥ Those who are unable to return to the hospital for further consultation and follow-up regularly according to the research plan;

              • Those who fail to comply with the research arrangement and sign the informed consent form; ⑧ Other conditions judged by the researcher not suitable for the group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CABA group; new artificial liver CABA system (BS330+CA280) combined with plasma exchange	Device: New artificial liver CABA system (BS330+CA280) +PE; The new artificial liver CABA system (BS330+CA280) combioned plasma exchange in the treatment of end-stage liver disease with inflammatory status; Other Names: standard drug therapy
Experimental: control group; BS330 combined with plasma exchange	Device: New artificial liver CABA system (BS330+CA280) +PE; The new artificial liver CABA system (BS330+CA280) combioned plasma exchange in the treatment of end-stage liver disease with inflammatory status; Other Names: standard drug therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
non-transplantation mortality	the 28-day and 90-day non-transplantation mortality	1 year

Collaborators and Investigators

• Sponsor: Qin Ning

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2023
• Primary Completion (Anticipated): March 8, 2024
• Study Completion (Anticipated): March 8, 2024

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 21, 2023
• First Posted (Actual): March 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Liver Diseases; End Stage Liver Disease; Inflammation
• Other Study ID Numbers: CABA STUDY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No