Figure 1.

Targeted 20% HAS infusions reverse immune dysfunction in AD/ACLF by improving ability of patients with AD/ACLF plasma to bind PGE₂. (A) Endotoxin (LPS) stimulated MDM TNF production in presence of patient plasma pretreatment with 20% HAS (n = 45 patients) compared with nonautologous healthy volunteer plasma. LPS MDMs TNF production in presence of healthy volunteer plasma was 6.88 ng/mL more in presence of AD plasma (CI, 4.85–8.91 ng/mL; P < .0001). (B) LPS MDM TNF production in presence of plasma pre- and post-HAS treatment (n = 45 patients incremented serum albumin >30 g/L). Mean post-treatment TNF increase 1.75 ng/mL (0.72–2.77; P = .0013), 14.5% (5.1%–23.5%). (C) Percentage PGE₂/³H-PGE₂ bound to healthy volunteer and AD/ACLF plasma protein using equilibrium dialysis. Post-HAS treatment plasma binds more PGE₂ than pre-HAS (mean increase, 8.7%; CI, 5.2%–12.1%; P < .0001; n = 45). (D) Percentage PGE₂/³H-PGE₂ bound in different HAS products or Sigma albumin diluted to 20 g/L albumin in phosphate-buffered saline (n = 3). (E) LPS MDM TNF production in presence of pretreatment patient plasma (n = 10) in presence/absence of EP2 (AH6890-50 μM) and EP4 (MF498-10 μM) receptor antagonists compared with post-treatment effect. (F) LPS MDM TNF production in presence of AD/ACLF plasma Day 5 and 10 post-treatment with 20% HAS.