Abstract
The present systematic review with meta-analysis was undertaken to review the evidence base in support of a beneficial effect of L-ornithine L-aspartate (LOLA) for the prevention/prophylaxis of overt hepatic encephalopathy (OHE) in patients with cirrhosis. Using appropriate keywords and electronic and manual searches together with established inclusion/exclusion criteria, six randomized controlled trials (RCTs) for a total of 384 patients were identified five of which were of high quality and low risk of bias according to Jadad-Cochrane criteria. Treatment with LOLA resulted in significant reductions in the risk of progression to OHE in MHE patients (3 studies) with RR: 0.23 [95% CI: 0.07, 0.73], p < 0.01. LOLA was also effective for secondary OHE prophylaxis with RR: 0.389 [95% CI: 0.174–0.870] p < 0.002 as well as for primary prophylaxis for OHE following acute variceal bleeding [RR: 0.42 [95% CI: 0.16–0.98] p < 0.03 and for OHE prophylaxis post-TIPSS [RR: 0.30 [95% CI: 0.03–2.66] compared to placebo/no intervention in all cases. OHE prevention/prophylaxis was accompanied by significant reductions of blood ammonia. Both oral and intravenous formulations of LOLA appeared to be effective for the prevention of progression to OHE in patients with MHE. These findings provide the first direct evidence of potential benefit of LOLA for the prevention of OHE in cirrhosis across a range of clinical presentations.
Highlights
Hepatic encephalopathy (HE) is a serious central nervous system (CNS) complication of cirrhosis characterized by a spectrum of neurological and neuropsychiatric symptoms whose appearance heralds a deteriorating medical condition
Four cirrhosis-related clinical presentations of overt hepatic encephalopathy (OHE) were identified in which details of L-ornithine L-aspartate (LOLA)-related prevention/ prophylaxis were provided namely the prevention of the progression of minimal HE (MHE) to OHE, the prevention of recurrence of OHE, primary prophylaxis aimed at the prevention of OHE associated with acute variceal bleeding and the prevention of OHE associated with the transjugular intrahepatic stent shunt (TIPSS) procedure
Results of the present systematic review and meta-analysis demonstrate, for the first time, that LOLA is effective for the prevention of OHE in patients with cirrhosis in a relatively wide spectrum of clinical presentations including decreased progression of MHE to OHE, prevention of the recurrence of OHE / secondary prophylaxis, primary OHE prophylaxis associated with acute variceal bleeding and post-TIPSS OHE prophylaxis
Summary
Hepatic encephalopathy (HE) is a serious central nervous system (CNS) complication of cirrhosis characterized by a spectrum of neurological and neuropsychiatric symptoms whose appearance heralds a deteriorating medical condition. Sporadic reports are limited in number to small sub-groups of very low numbers of trials and patients but results so far are inconsistent (Goh et al 2018; Thumburu et al 2017) Given this paucity of available data and as a basis for planned research in this area, the present systematic review with meta-analysis was undertaken in order to review the evidence base in support of a beneficial effect of LOLA for OHE prevention/prophylaxis in patients with cirrhosis. The analysis aimed to compare effects of LOLA (oral or intravenous formulations) compared to placebo/no intervention in randomized controlled clinical trials (RCTs) with adequate description of patient characteristics, blinding of personnel, patients, investigators, numbers of dropouts, dose and route of administration of LOLA or placebo in sufficient detail for assessment of trial quality and risk of biases as previously reported (Butterworth et al 2018). Aggregations of the results of the primary studies were made using the Random Effects model in all cases
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