Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: Results of a placebo-controlled, double-blind study

Abstract

prandial venous ammonia concentrations in the OAOne hundred twenty-six patients with cirrhosis, hytreated group showed improvements in comparison perammonemia (ú50 mmol/L), and chronic (persistent) with placebo. In addition, venous fasting blood ammonia hepatic encephalopathy (HE), which developed spontaconcentration (P õ .01), mental state gradation (P õ neously without the existence of known precipitating .001), and PSEI (P õ .01), which includes the mental state factors, were enrolled in a randomized, double-blind, gradation, NCT-A time, and postprandial venous ammoplacebo-controlled clinical trial of intravenously adminnia in this trial, improved to a much higher degree in Hepatic encephalopathy (HE) is one of the major complicapresented are based on the total study sample (intent-to-tions of cirrhosis. Five years after the diagnosis of cirrhosis, treat analysis), which included 63 patients in the placebo the probability of developing at least one episode of this spegroup and 63 patients in the OA group. Of the 126 pa-cific form of decompensated cirrhosis is in the range of 26%. 1 tients, 114 met all the criteria for inclusion and com-Once clinical decompensation has occurred, however, the pleted the trial and treatment as outlined in the protocol prognosis (16% 1 to 22% 2 probability of survival at 5 years) (treated-per-protocol analysis). During baseline, the pla-compared with a survival probability of 55% 2 to 70% 1 in circebo and treatment groups were homogeneous with re-rhotic patients without HE is very poor. 1,2 Therefore, prevengard to mental states, NCT-A performance time, fasting tion and effective treatment of HE may have important progvenous blood ammonia levels, and Child-Pugh criteria. nostic implications in cirrhotic patients. Although a slight improvement occurred in the placeboHyperammonemia 3,4 by a variety of postulated mechagroup, NCT-A performance times (P õ .001) and post-nisms 3-8 is felt to be one of the primary pathogenetic factors in the development of HE. 8 The majority of therapeutic measures currently in use are therefore directed at reducing blood Abbreviations: HE, hepatic encephalopathy; SHE, subclinical hepatic encephalopathy; ammonia levels, 9-13 mainly by diminishing enteric ammonia OA, L-ornithine-L-aspartate; GS, glutamine synthetase; NCT-A, number connection test A; PSEI, portal systemic encephalopathy index.production. Otherwise, it is known that liver and muscle play From the 1 Martin-Luther-University Halle-Wittenberg, Department of Internal Median important part within the ammonia detoxification system, cine, Halle;

Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy

“…[15][16][17] Several treatment modalities that reduce ammonia level have been tried in order to treat this condition, for example, dietary protein manipulation, 18 branched-chain amino acids, 19 L-ornithine L-aspartate, 20 lactulose, 21,22,46 and probiotics. 23 Most of the studies of these treatment modalities have found improvement in psychometry, [19][20][21][22][23] ammonia level, 20,23,24 and cerebral edema. 46 We did not measure ammonia level in our patients; however, we believe that improvement in the MHE in our patients most likely was related to the same mechanism.…”

“…[15][16][17] Therapeutic interventions that aim to reduce ammonia are also useful in this setting. [18][19][20][21][22][23][24] Most studies have shown improvement in psychomotor functions coupled with a reduction in ammonia level. Improvement in cognitive functions may translate into improvement in HRQOL.…”

L -Ornithine- L -aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure

“…8 L-Ornithine-L-aspartate (OA) has been proven to be effective in lowering blood ammonia concentrations in both experimental and human chronic liver failure. [9][10][11] A recent randomized, clinical trial of OA treatment revealed significant reductions in blood ammonia in cirrhotic patients concomitant with a significant improvement of neuropsychiatric symptoms. 10 In view of these findings and of the proposed role of ammonia in the pathogenesis of brain edema in ALF, the present study had 2 aims, namely: 1) to study the efficacy of OA in the prevention of encephalopathy and brain edema in experimental ALF; and 2) to relate this protective effect of OA to altered plasma and cerebrospinal fluid (CSF) concentrations of ammonia and ammonia-related metabolites as well as activities of the ammonia-related enzyme, glutamine synthetase.…”

Management of Overt Hepatic Encephalopathy

“…39 These findings point to L-ornithine-L-aspartate (LOLA) as a promising HE treatment that deserves further evaluation. 42 Metaanalysis of eight randomized controlled trials with 646 patients comparing placebo/no-intervention control, LOLA was significantly more effective in the improvement of HE in the total (RR: 1.49, 95% confidence interval [CI]: 1.10-2.01), overt HE (RR: 1.33, 95% CI: 1.04-1.69). The tolerance ratio, incidence of adverse events, and mortality were not significantly different between LOLA and the placebo/nointervention control.…”