Ammonia Removal During Plasma Exchange in ACLF
Yes, ammonia is effectively removed during plasma exchange (PLEX) in patients with acute-on-chronic liver failure (ACLF), with studies demonstrating significant reductions in plasma ammonia levels that correlate with improved survival and reduced hepatic encephalopathy severity. 1
Evidence for Ammonia Removal
Direct ammonia reduction has been documented in ACLF patients treated with PLEX, showing more dramatic decreases compared to standard medical therapy alone. In a controlled study, PLEX survivors demonstrated ammonia reduction from 116.8 ± 36.3 to 44.8 ± 16.3 μmol/L after 30 days, compared to medical therapy survivors who only decreased from 105.7 ± 30.2 to 57.1 ± 20.3 μmol/L (p < 0.05). 1 Importantly, ammonia levels remained significantly lower in the PLEX group even after treatment completion. 1
Elevated ammonia levels are independently associated with mortality in ACLF patients, making ammonia removal a clinically relevant therapeutic target. 1 The mechanism by which PLEX improves survival in acute liver failure includes ameliorating the release of ammonia from the necrotic liver. 2
Clinical Context and Guidelines
However, routine ammonia level testing is not recommended for diagnosis or monitoring of hepatic encephalopathy in ACLF patients. 3 The 2024 AASLD guidance explicitly states that ammonia levels are variable within patients and laboratories, and may be elevated in non-HE conditions. 3 A low ammonia level in patients with coma or confusion should point toward etiologies other than hepatic encephalopathy. 3
Despite ammonia removal being a documented effect of PLEX, major guidelines do not recommend routine PLEX for ACLF outside research protocols. 4 The EASL explicitly recommends against routine use of plasma exchange for ACLF outside of research trials, citing insufficient high-quality evidence. 4 The AASLD suggests plasma exchange only for acute liver failure with hyperammonemia, not for ACLF. 4
Pathophysiological Significance
Ammonia plays a critical role in the pathogenesis of brain dysfunction in ACLF, along with inflammation and abnormal cerebral oxygenation. 5 Hyperammonemia is associated with both the presence and severity of hepatic encephalopathy in ACLF patients. 5 Improvement in ammonia levels correlates with reduction in hepatic encephalopathy grade. 5
In acute liver failure (distinct from ACLF), arterial ammonia levels ≥200 μg/dL are strongly associated with cerebral herniation. 3 This has led to consideration of ammonia-lowering strategies, though lactulose's role in acute liver failure remains unclear. 3
Clinical Implications
While PLEX does remove ammonia and may improve outcomes, the decision to use PLEX in ACLF should be based on broader criteria than ammonia levels alone. 4 Consider PLEX only in ACLF patients who are:
- Listed for liver transplantation 4
- Deteriorating despite standard medical therapy 4
- At a center with PLEX expertise 4
- Ideally enrolled in a research protocol 4
Standard management of hepatic encephalopathy in ACLF remains lactulose or polyethylene glycol, with rifaximin as adjunctive therapy. 3 These treatments target ammonia through different mechanisms than PLEX and should be initiated regardless of PLEX consideration. 3