Hepatic Encephalopathy and Albumin Lasting Cognitive Improvement

In outpatients with cirrhosis with prior HE who have cognitive impairment despite adequate therapy, how long the impact of albumin lasts and through which potential mechanism(s) needs to be determined.

A prior recent HEAL trial showed that patients with prior HE and current minimal hepatic encephalopathy (MHE) randomized to albumin experienced significant improvement in cognitive dysfunction and psychosocial quality of life. Moreover, these improvements persisted a week after the last albumin infusion, which was not seen in the placebo group. This was accompanied by an improvement in endothelial dysfunction, ischemia-modified albumin levels and inflammatory markers that persisted one week even after albumin discontinuation. The reported half-life of IV albumin is 2 weeks, but the function and the length of time of albumin's action in decompensated cirrhosis is lower, and further details surrounding albumin pharmacokinetics in this population remain unelucidated. The mechanisms and length of time albumin's potential improvement for patients with MHE after treatment discontinuation also require continued study.

Study design:

This will be a single-arm, single-blind sequential trial of IV 25% albumin and IV saline over 8 weeks with biological sampling and cognitive and health related quality of life (HRQOL) testing with each subject acting as their own control.

Th order of the albumin and placebo infusion and blind the infusions from the subjects and the assessors of the outcomes will be changed.

• EncephalApp Stroop change in Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Critical Flicker Frequency change in Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in Sickness Impact Profile Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in PROMIS-29 Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in MELD-Na score Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in endotoxin binding protein Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in oxidized albumin Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in ischemia modified albumin Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in stool bile acids Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in serum bile acids Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in serum Short-chain fatty acids Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]
• Change in stool Short-chain fatty acids Placebo phase vs Albumin phase [Срок оценки: 4 weeks each]