Artificial Liver Support Systems

1. Artificial Liver Support Systems John McLinden Biomedical Engineering

2. A Brief Introduction • Liver failure leads to a buildup of toxins in the bloodstream • Artificial liver support systems attempt to remove these toxins to increase survival times • Ultimately, liver can repair itself or a transplant is needed • Most early artificial liver support systems insufficient[1]

3. MARS and PDF • Molecular Adsorption and Recycling System (MARS) was among the first artificial liver support systems to show true promise • Used human albumin as a substrate[1] • Plasma diafiltration (PDF) is a newer, experimental system • Also uses albumin, but exchanges blood plasma and was developed to allow the passage of adiponectin (APN)[2]

4. MARS Overview • Blood is pumped through an impermeable hollow fiber dialyzer with albumin containing dialysate • The molecules captured are filtered through a charcoal and anion exchange columns • Dialysate also goes through a single-pass dialyzer[3] http://onlinelibrary.wiley.com.uri.idm.oclc.org/doi/10.1053/jhep.2002.36130/pdf

5. PDF Overview • Uses an anticoagulant, dialysate, replacement fluid, and a human plasma/albumin mixture • Also uses a membrane that allows the passage of APN, which is believed to have anti-inflammatory properties[2] http://onlinelibrary.wiley.com.uri.idm.oclc.org/doi/10.1111/1744-9987.12344/pdf

6. MARS Results • Some studies reported increases in 30-day survivability compared to standard medical procedure[4] • One reported that MARS patients experienced an 8.3% mortality rate versus patients receiving standard medical treatment, who experienced a 50% mortality rate[3]

7. MARS Results Cont. • However, recent reviews of multiple MARS studies claim that the system does not have a significant effect on 30-day survivability • It is possible that the data were skewed because sepsis may have begun before the treatments were administered, which is a significant complication.[4]

8. PDF Results • PDF saw a significant increase in median APN levels (11.64μg/mL before PDF to 14.52μg/mL after PDF) • For comparison, plasma exchange (PE) patients experienced a drop in median APN levels (11.53μg/mL before PE to 7.22μg/mL after)[2] http://onlinelibrary.wiley.com.uri.idm.oclc.org/doi/10.1111/1744-9987.12344/pdf

9. PDF Results Cont. • However, increased pore size of the membrane could have allowed inflammatory cytokines through as well • These could mitigate the beneficial effects of APN[2]

10. Conclusion • MARS has been tested for many years, with mixed results • Further testing is required to understand the conditions under which MARS would be most effective[4] • PDF was able to significantly increase APN levels, but requires more research to determine if it will ever become common practice[2]

11. References • [1] Maiwall, R. et. al. Liver dialysis in acute-on-chronic liver failure: current and future perspectives. Hepatology International, 8(2): 505-13, 2014. • [2] Yamamoto, H. et. al. Plasma adiponectin levels in acute liver failure patients treated with plasma filtration with dialysis and plasma exchange. Therapeutic Apheresis and Dialysis, 19(4): 349-353, 2015. • [3] HassaneinT. et. al. Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study. Hepatology, 36 (4): 949-58 2002. • [4] Wauters, J. & Wilmer, A. Albumin dialysis: current practice and future options. Liver International, 31 (s3): 9-12 2011.

12. Questions?