Abstract
Clinical feasibility phase-I study data are discussed on the use and the safety of a modular mass exchanger for temporary extracorporeal treatment of liver failure; and the use of the cell source primary human liver cells isolated from discarded transplant organs as a metabolic module in this mass exchanger. This technology platform can be compared with the mass exchange functions of a human placenta before giving birth. The "maternal blood side" can be used with various sources/modules of metabolic support including artificial (e.g. absorber) or biological elements (e.g. cells), separated by membrane compartments. These keep the source of metabolic support from contact with the patient, including the immune cells, while allowing exchange of soluble or protein-bound plasma components for therapy. Each of the multiple independent membrane compartments are bundled towards the in/outlets but interwoven to form a decentralized multi-compartment mass exchanger within an effector module compartment. The use of liver cells as a metabolic module in this compartment results in its function as a bioreactor. A combination with further modules outside of the mass exchanger was demonstrated through a continuous SPAD for detoxification. Nine patients (5 m, 4 f) with a median age of 43 years (range 11-55 years) were treated with a total of 11 metabolic modules in 12 sessions, with overall treatment times ranging from 11 to 216 hours. Patients suffered from acute-on-chronic liver failure (AoCLF, n=3), acute liver failure (ALF, n=3) and primary non-function graft after liver transplantation (PNF, n=3). Treatment resulted in a one-year survival of 78%. The results showed a significant decrease in thrombocytes and fibrinogen. No severe adverse effects were found. One patient (AoCLF) recovered without transplantation and remained alive for the one-year follow-up. Six patients (3 ALF, 2 PNF, and 1 AoCLF) were successfully bridged to transplantation, and two (1 AoCLF, 1 PNF) died within ten days after termination of therapy. Total and conjugated bilirubin, ammonia, urea and creatinine were significantly reduced by the end of therapy, compared to baseline. The MELD score decreased significantly, whereas no significant improvements were observed in APACHE-II, APACHE-III, SOFA and Child-Pugh scores.
Conclusion: The mass exchanger technology platform, the Core Module used with primary human liver cells as Metabolic Module, proved to be clinically feasible and safe. Further clinical studies are required to prove the efficacy of such therapies. However, the clinical impact of using human liver cells as a Metabolic Module is limited and a reliable, biocompatible and effective metabolic source is in need.