**9. Plasma exchange**

The plasma exchange (PE) is an extracorporeal purification technique that is carried out by centrifugation or filtration. This last technique uses a high permeability membrane with a large pore size greater than 0.3 microns, allowing the separation of plasma and the removal of medium and medium molecules with high molecular weight, such as cytokines and immunoglobulins (**Figure 8**).

Within the pathophysiological mechanisms of acute and chronic liver injury, the increase in Von Willebrand multimeters stands out due to a decrease in the release of ADAMTS 13 as a result of stellate cell damage. The increase in the Von Willebrand factor multimeters intervenes in platelet aggregation in the hepatic sinusoids and conditions the migration of macrophages for their phagocytosis, and both alterations condition a deterioration of the vascular flow of the liver and also condition a greater inflammatory response.

#### **Figure 8.**

*Plasma exchange (PE). The technique uses a high permeability membrane with a large pore size that allows plasma separation and replacement of the extracted volume is performed with 5% albumin or fresh frozen plasma.*

Klaus Stahl et al. [43], in a single-center prospective study, demonstrated in 31 patients with sepsis that plasma exchange increased ADAMTS 13 activity and decreased VWF antigen, confirming the therapeutic application of this imbalance.

The RCT described by Larsen et al. [44], through an RCT in 182 patients with ALF, evaluated SMT vs. SMT and high volume plasma exchange for 3 days (8–12 L) with replacement with fresh-frozen plasma in equivalent volume. In the consulted evidence, the primary outcome that corresponds to liver transplant-free survival during the hospital stay was higher in the group that received plasma exchange (p = 0.0083), and survival in those who did not receive a transplant and received plasma exchange was better when compared with those who were not transplanted and did not receive plasma exchange. In the group with plasma exchange, the hemodynamic variables improved, noradrenaline doses were reduced, the SOFA and Clif SOFA severity scores improved, and the analysis showed improvement in coagulation times, decreased bilirubin, alanine aminotransferase (ALT), and ammonium. When the inflammatory response is assessed, plasma exchange reduces DAMPs, TNF alpha, IL 16 at 48 hours, and IL 18, and decreases in CD 163, CD 64, and CCR7, which indicates less mononuclear cell traffic.

High-volume plasma exchange carries risks with high replacement volume and could worsen cerebral edema, Maiwall et al. [45], report a prospective open-label RCT study where 40 patients with ALF were recruited, each group was divided into 20 patients for SMT vs STM and standard plasma exchange (1–1.5 plasma volumes per PE session). The outcome of transplant-free survival at 21 days was higher in the group with plasma exchange (p 0.04). In the secondary outcomes, there is evidence of a lower inflammatory response and a smaller diameter of the optic nerve sheath with a predictor of decreased cerebral edema, hemodynamic variables, vascular resistance index improved, SOFA score decreased, there was a decrease in lactate and bilirubin values they also decreased. When inflammation data are analyzed, a decrease in innate immunity cytokines and an increase in anti-inflammatory cytokines, a significant decrease in DAMPs, endotoxins, and a decrease in VWF are evident in the group that received exchange plasma.

In a retrospective study [46] of 50 patients with alcohol-related acute on chronic liver failure (A-ACLF), low-dose corticosteroid treatment was compared *Artificial Liver Support Systems DOI: http://dx.doi.org/10.5772/intechopen.109843*


**Table 5.**

*PALS score predictive score of short-term prognosis for patients treated with plasma exchange.*

with low-volume plasma exchange (LVPE) (0.5–1 plasma volumes per PE session) vs. SMT, Kaplan-Meier survival analysis shows better survival in the first year (P = 0.03) and there were lower levels of VWF in the plasma exchange group. Further large randomized control trials are needed to evaluate the efficacy of LVPE in ACLF.

In a systematic review and meta-analysis [47] of 16 RCTs that included 1670 patients with ALF, the efficiency of each therapy was compared to SMT, ELAD, MARS, Prometheus, and plasma exchange. It is shown that the probability of having greater overall survival at the first and third month as well as transplant-free survival at 3 months was better with exchange plasma.

The European Association for the Study of the Liver [11], in the guidelines for the management of acute liver failure, recommends plasma exchange improves transplant-free survival and modulates immune dysfunction with evidence level I, grade of recommendation 1. and recommends early onset and in those who will not undergo liver transplantation with evidence level I, grade of recommendation 2.

One DELPHI consensus of international experts [35] recently published, in relation to PEHV, is recommended due to the greater transplant-free and in-hospital survival. The PLAS score [48] uses two derivation and validation cohorts of patients with ACLF, whose predictive value for 3-month mortality when the score was greater than 6 points (AUC 0.80 derivation cohort and 0.78 validation cohort) has better performance when it is compared with the model for end-stage liver disease (MELD) and also with other mortality scores. The variables taken into account for stratification are liver cirrhosis total bilirubin, PT-INR, infection, and hepatic encephalopathy. The score goes from a minimum of 0 to a maximum of 9, it is called grade I: score of 0–2, grade II: 3–5, grade III: 6–9 (**Table 5**).

Extracorporeal liver support therapy is not recommended in patients who develop platelet counts <40,000/mm3, INR > 2.5, and fibrinogen <1 g/L, which would increase the risk of bleeding [35].
