Randomised clinical trial:l-ornithine-l-aspartate reduces significantly the increase of venous ammonia concentration after TIPSS

Abstract

SUMMARY BackgroundUse of TIPSS is associated with increases in ammonia concentration and hepatic encephalopathy (HE) risk. L-ornithine-L-aspartate (LOLA) is effective in reducing ammonia concentration.

Effects of supplementation with branched chain amino acids and ornithine aspartate on plasma ammonia and central fatigue during exercise in healthy men

“…Supplements based on proteins and amino acids are currently one of the most overused and overdosed, so any recommendations for their use should be calculated very carefully. In certain cases the use of OA seems to be rational and in agreement with the results of most studies [1,7,8,11,42,44]; however, some critical works are also present [2,45].…”

l-Ornithine l-Aspartate (LOLA) for Hepatic Encephalopathy in Cirrhosis: Results of Randomized Controlled Trials and Meta-Analyses

“…Previous studies demonstrate substantial increases of liver transaminase enzymes and bilirubin indicative of hepatocellular injury following TIPSS. However, following LOLA treatment the increases in transaminases and bilirubin were significantly attenuated as were increases in MELD scores consistent with the notion that a 7-day prophylactic use of LOLA alleviates post-TIPSS hepatic injury [24]. Novel mechanisms have been proposed to explain these hepato-protective actions of LOLA in patients with cirrhosis [25].…”

“…A crossover study in seven patients with previous TIPSS concluded that a single 5 g dose of LOLA was not effective for alleviation of the acute hyperammonemia resulting from a 20 g glutamine challenge [23]. In contrast, a subsequent RCT of 40 TIPSS patients demonstrated that prophylactic use of intravenous LOLA 30 g/day for 7 consecutive days was effective in significantly lowering both fasting and postprandial ammonia concentrations [24]. Moreover, psychometric testing using number connection test NCT-A, serial dotting test and line tracing test were all significantly improved in patients in the LOLA treatment group compared to control at days 1, 3 and 7 and patients in the LOLA group tended to have a slower progression to OHE.…”

Is it time to target gut dysbiosis and immune dysfunction in the therapy of hepatic encephalopathy?

“…Antibiotics such as neomycin, metronidazole and vancomycin have been used with the aim of reducing the production of ammonia by gut microbiota, but their long-term use has been associated with adverse side effects of nephrotoxicity, ototoxicity and peripheral neuropathy. Selective gut decontamination may therefore have utility, but this does not, however, explain why germ-free animals whose guts have been totally irradiated still develop HE and why therapies such as glyceryl phenylbutyrate [23], L-ornithine L-aspartate [24] and L-ornithine phenylacetate [25], which increase ammonia removal, are efficacious. This indicates that other pathophysiological factors may also have importance, including the presence of phosphate-activating glutaminase in enterocytes resulting in net ammonia production and the impact that systemic inflammation alone has on neurocognitive function in those without evidence of liver disease, such as those with septic encephalopathy or delirium [20].…”