Hyperdynamic circulation and portal hypertension characterize acute on chronic liver failure (AoCLF), partially because of circulating mediators. Molecular Absorbents Recirculating System (MARS) may remove some of these substances. The objective of this study was to evaluate the effect of MARS on portal pressure, systemic haemodynamic and endogenous vasoactive systems. MARS treatment was performed in four patients with AoCLF (mean age 36.2 +/- 3.1 years; Child-Pugh C 11 +/- 1.8 points; three AAH and one NASH). Systemic and splanchnic haemodynamic measurements were performed before and after each session. Plasmatic renin activity (PRA) and NE were measured at baseline, at the end of the sessions and 10 days after MARS. All patients had severe portal hypertension (HVPG=23 +/- 7 mmHg) and pronounced hyperdynamic circulation (MAP 77.8 +/- 11.7 mmHg; CO 11.2 +/- 1.6 L/min; SVRI 478.5 +/- 105 dyne s/cm5). HVPG decreased at the end of the first session in all patients (23 +/- 7 mmHg vs 17.3 +/- 9.9 mmHg; P=0.05; mean decrease 32 +/- 24%) because of a decrease in WHVP (40.7 +/- 5.6 mmHg vs 34 +/- 9.6 mmHg; P=0.025; mean decrease 18 +/- 19%). MARS significantly attenuated hyperdynamic circulation as shown by a decrease in CO (11.2 +/- 1.6 L/min vs 9.4 +/- 2.1 L/min; mean decrease 12.3%), with an increase in MAP (77.8 +/- 11.7 mmHg vs 84.2 +/- 8 mmHg; mean increase 9.2%) and in SVRI (478.5 +/- 105 dyne s/cm5 vs 622 +/- 198 dyne s/cm5; mean increase 41%). PRA and NE decreased significantly (14.2 +/- 17.2 ng/mL/h vs 3.7 +/- 3.4 ng/mL/h; 1319 +/- 1002 pg/mL vs 617 +/- 260 pg/mL, respectively). The NE decrease was correlated to HVPG decrease (r=1, P=0.01). MARS decreases portal hypertension and ameliorates hyperdynamic circulation in patients with AoCLF, probably mediated by clearance of vasoactive substances. Further studies are necessary to confirm these results.