**12. Coupled plasma filtration with adsorption**

Coupled plasma filtration with adsorption (CPFA) is a technique, which requires a CRRT machine (Amplya), especially designed to combine the separation of plasma from blood by a high-permeability polyethersulfone filter. Then, the separated plasma circulates through a styrene cartridge-divinylbenzene copolymer and the purified plasma is reconstituted with the blood, which is finally returned to a CRRT polyphenylene hemofilter to remove water-soluble molecules (**Figure 11**).

#### **Figure 11.**

*Coupled plasma filtration with adsorption (CPFA). A) Requires the separation of plasma from blood by a high-permeability polyethersulfone filter. B) The separated plasma is circulated through a styrene-divinylbenzene copolymer cartrige. C) The purified plasma is reconstituted with the blood, which is finally returned to a CRRT polyphenylene hemofilter.*

The Hercole trail [54], a non-randomized observational study that included 12 patients, 4 with ALF and 8 with ACLF, started APFC with total bilirubin values > 20 mg/dl and MELD >20 that did not improve with SMT. It is observed that CPFA did not modify the SOFA and MELD score, the decrease in bilirubin (p = 0.0006) and bile acids (p = 0.047) decreased significantly, but after the third hour, the filter was saturated. Water-soluble molecules, such as water-soluble toxins, urea, and creatinine, did not change significantly before or after PAFC, attributed to low convective volumes, INR and aPTT values were prolonged, but bleeding was not reported. It is important to mention that bilirubin rebound is expected to occur after the first session and ranges from 10 to 40% and is characteristic of the multicompartmental model of bilirubin kinetics, which occurs in any of the aforementioned therapies. It is a promising therapy, which requires further evidence with randomized controlled trials.
