Indications for L-Ornithine L-Aspartate (LOLA)
LOLA is indicated for the treatment of overt hepatic encephalopathy in patients with acute-on-chronic liver failure (ACLF), administered intravenously at 30 g/day. 1, 2
Primary Indication: Overt Hepatic Encephalopathy in ACLF
LOLA should be used in critically ill ACLF patients with overt hepatic encephalopathy as a conditional recommendation based on very low quality evidence from the 2023 Critical Care Medicine guidelines 1
The medication works as a substrate for the urea cycle, stimulating enzymatic activity in residual hepatocytes to increase ammonia detoxification and urea excretion 1
Intravenous administration at 30 g/day is the recommended dose for patients with hepatic encephalopathy 1, 2
Specific Clinical Scenarios
West-Haven Grade 1-2 Hepatic Encephalopathy
- For patients with West-Haven criteria grade 1-2 hepatic encephalopathy, intravenous LOLA is more effective than placebo in lowering number connection test (NCT-A) time and plasma ammonia concentrations 1
Combination Therapy
- LOLA can be combined with lactulose for enhanced efficacy, with studies showing patients treated with lactulose plus intravenous LOLA (30 g/day) achieving lower grades of hepatic encephalopathy within 1-4 days (OR 2.06-3.04) and shorter duration until symptom recovery (1.92 vs 2.50 days) compared to lactulose alone 1, 3
Alternative/Add-on Therapy
LOLA serves as a third-line agent after lactulose and rifaximin for hepatic encephalopathy management 1, 2
The 2014 EASL/AASLD guidelines recommend intravenous LOLA as an alternative or additional agent for patients nonresponsive to conventional therapy (GRADE I, B, 2) 1, 2
Important Limitations and Contraindications
NOT Indicated For:
LOLA is NOT recommended for acute liver failure (ALF) patients with hyperammonemia - there is insufficient evidence to support its use in this population 1
Oral LOLA supplementation is ineffective and should not be used, according to major guidelines 1, 2
Route of Administration Matters:
Only intravenous administration has proven efficacy in improving psychometric testing and reducing postprandial venous ammonia levels in patients with persistent hepatic encephalopathy 1
While oral LOLA may lower NCT-A time and plasma ammonia concentrations, further studies are required to assess its efficacy in managing overt hepatic encephalopathy 1
Geographic and Availability Considerations
LOLA is more frequently used outside the United States for treatment of hepatic encephalopathy 1
The medication has a favorable safety profile with no specific contraindications documented in major guidelines 2
LOLA demonstrates better safety compared to antibiotics like neomycin and metronidazole, which carry risks of nephrotoxicity, ototoxicity, and peripheral neuropathy 1
Clinical Evidence Quality
A systematic review of six RCTs (n=597) suggested possible beneficial effects of LOLA on mortality, hepatic encephalopathy, and serious adverse events compared to placebo, though the quality of evidence was very low 1
The strongest evidence comes from a 2018 prospective, double-blind RCT showing that intravenous LOLA as add-on therapy significantly improved hepatic encephalopathy grades over days 1-4, decreased venous ammonia, reduced time to recovery, and shortened hospital stay 3