IMMUNOMODULATORY EFFECT OF DOUBLE PLASMA MOLECULAR ABSORPTION SYSTEM IN PATIENT WITH ACUTE-ON-CHRONIC LIVER FAILURE

The Double Plasma Molecular Adsorption Recirculating System (DPMAS) is an extracorporeal liver support system designed to remove albumin-bound toxins and inflammatory cytokines using dual adsorbent columns. In acute-on-chronic liver disease (ACLF), the surge of proinflammatory cytokines may lead to multiorgan failure and more liver injury. By removing these mediators, DPMAS may has an immunomodulating effect which reduce systemic inflammation and attenuate the severity of disease. We investigated the effect of DPMAS on clinical and inflammatory markers in patients with ACLF.

We conducted a multicenter, randomized controlled trial in patients with ACLF with hepatic encephalopathy (HE) at least grade 2 who admitted to the ICU. Patients were randomized to receive either DPMAS for 3 consecutive daysplus standard therapy or standard therapy alone according to EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure 2017. We used blood flow rate of 100-120 ml/hour with filtration fraction for plasma separation of 25-30%. DPMAS circuit consist of Plasmaflo OP cartridge (Asahi Medical, Tokyo, Japan), Ion exchange resin hemoperfusion cartridge (BS330; Jafron, Zhuhai City, China), and Neutral adsorption resin hemoperfusion cartridge (HA330-II; Jafron, Zhuhai City, China). We did not use any anticoagulant. The primary outcome was the change of mHLA-DR expression, and CD11b expression between day 3 and baseline. Secondary outcomes are 28 days survival rate, total bilirubin redution, and HE grading. Statistical comparisons between groups were made using the Chi-square test for categorical data and the Wilcoxon rank-sum test for continuous data.

Twenty-five patients (52% male, median age 55 years, median Child-Pugh score of 8) were randomized to the DPMAS (n=15) and placebo (n=10) groups. The most common cause of cirrhosis were alcohol and chronic hepatitis B, with upper gastrointestinal bleeding being the most precipitating cause. Baseline characteristics, including disease severity scores, were comparable between the groups. The DPMAS group showed a significant reduction in median total bilirubin from 28 mg/dL at baseline to 20 mg/dL on day 3, whereas the placebo group showed a slight increase from 20 mg/dL to 22 mg/dL (p-value for change between groups=0.002). A similar significant reduction was observed for direct bilirubin (p=0.004). Regarding immunological markers, there was a trend towards a decrease in CD11b % expression in the DPMAS group and an increase in the placebo group; however, this difference in change between the groups was not statistically significant (p=0.14). In contrast, there was no significant change in mHLA-DR % expression between the groups (Figure). Furthermore, no significant differences were observed in 28-day mortality (20% vs 40%; p=0.48), HE grade, or changes in SOFA and APACHE II scores.

In patients with ACLF, using DPMAS significantly results in decrease total and direct bilirubin. There was a trend towards reduced neutrophil activation in the DPMAS group, as suggested by the decrease in CD11b expression. Further studies are warranted to assess whether these biochemical improvements translate to improved clinical outcomes.