Abstract: FR-PO135
Role of Immunomodulation Therapy with Selective Cytopheretic Device (SCD) in Reversing Acute on Chronic Liver Failure (ACLF) with Hepatorenal Syndrome (HRS) and Multi-Organ Failure
Session Information
- AKI: Outcomes, RRT
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Yessayan, Lenar Tatios, University of Michigan, Ann Arbor, Michigan, United States
- Sharma, Pratima, University of Michigan, Ann Arbor, Michigan, United States
- Westover, Angela, University of Michigan, Ann Arbor, Michigan, United States
- Szamosfalvi, Balazs, University of Michigan, Ann Arbor, Michigan, United States
- Humes, H. David, University of Michigan, Ann Arbor, Michigan, United States
Introduction
ACLF is a clinical disorder characterized by acute clinical deterioration in patients with pre-existing chronic liver disease. ACLF develops from systemic inflammation, often due to bacterial infections or alcoholic hepatitis, and progresses to multi-organ failure. Severe ACLF with ≥ 4 organ failure has a grave prognosis with a mortality rate at 28 days of 100%. Early liver transplant is the treatment of choice for those who are refractory to medical treatment. Intervention to modulate and lessen this systemic inflammatory state may alter the progression of multi-organ dysfunction and allow time for liver transplantation.
Case Description
Case 1. A male patient in his 30s presented with acute alcohol associated hepatitis, ACLF, HRS, and ≥4 organ failure. He required vasopressors, mechanical ventilation, and CKRT. MELD score was 38. Case 2. A male patient in his 60s with non-alcoholic steatohepatitis (NASH) was admitted for hypotension and decompensated cirrhosis. He required vasopressors and developed HRS. MELD score was 37. Both patients were enrolled into a clinical trial (NCT 04898010) to evaluate an extracorporeal immunomodulating device, SCD. Both patients showed rapid clinical improvement associated with a decline in elevated blood cytokine concentrations and diminution of activation levels of circulating leukocytes. On follow up Case 1 was alive at day 90 after treatment and undergoing liver transplantation evaluation and Case 2 had a successful liver transplantation 6 days after SCD therapy ended.
Discussion
The final common pathway of systemic hyper-inflammation resulting in multi-organ failure is the effector cells of the innate immunologic system. The activation of neutrophils and monocytes is the key driver of the developing hypoxic and toxic tissue damage of solid organs. The immunomodulation of these cellular elements rather than removal or inhibition of soluble cytokines or chemokines of inflammation is the critical target for effective therapy, as demonstrated with SCD treatment.
These cases represent the first in human treatment of ACLF with SCD. These results suggest a role for SCD treatment in the management of HRS-AKI and ACLF as a bridge to liver transplantation.