1. 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/jh ep.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 14.52 μg/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.o clc.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] Hassanein T. 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?