Effect of rifaximin, probiotics, and l-ornithine l-aspartate on minimal hepatic encephalopathy: A randomized controlled trial

Abstract

Background/Aims:Minimal hepatic encephalopathy (MHE) implies subtle impairment of cognitive functions in the absence of features of overt encephalopathy. We aimed to determine the prevalence of MHE in patients with liver cirrhosis and to find out the effect of rifaximin, probiotics, and l-ornithine l-aspartate (LOLA) individually in reversal of MHE by comparing it with placebo group.Patients and Methods:This study was carried out in two phases. Phase I included the recruitment of 250 apparently healthy controls and extraction of normative data utilizing three neuropsychometric tests (NPTs) and critical flicker frequency (CFF) test. Phase II consisted of screening and recruitment of patients of MHE followed by drugs trial. A total of 317 cirrhotics were screened; 111 were excluded and the remaining 206 cirrhotics were screened for MHE using NPTs and/or CFF test. Of these, 124 patients with MHE were randomized to receive LOLA (n = 31), rifaximin (n = 31), probiotics (n = 32), for 2 months and were compared with patients who were given placebo (n = 30).Results:Out of 206 cirrhotics, 124 (60.19%) had MHE. Among these 124 MHE patients, 87 (70.16%) patients had CFF <39Hz, 112 (90.32%) patients with MHE had two or more abnormal NPTs, and 75 (60.48%) patients had abnormality on both the CFF values and more than two abnormal NPTs. Intention-to-treat analysis showed the number of patients who improved after giving treatment were 67.7% (21/31), 70.9% (22/31), 50% (16/32), and 30% (9/30) for LOLA, rifaximin, probiotics, and placebo, respectively. CFF scores and improvement in psychometric tests after treatment were significantly higher (P < 0.05) for LOLA, rifaximin, and probiotics as compared with placebo group.Conclusions:Prevalence of MHE is high in patients with cirrhosis of liver. Rifaximin, LOLA, and probiotics are better than giving placebo in patients with MHE.

Kinetic mutations in argininosuccinate synthetase deficiency: characterisation and in vitro correction by substrate supplementation

“…Therefore, substrate supplementation, even if not reaching saturating concentrations intracellularly, would increase the activity of these kinetic mutations to different extents (depending on the K m for aspartate of each specific mutation). l -Aspartate, as l -ornithine- l -aspartate, is an already available drug currently used for treatment of hepatic encephalopathy 26 27. Thus, it could potentially be directly implemented in clinics to treat patients with citrullinemia type 1 with decreased affinity for aspartate.…”

Retracted: Efficacy of different drugs in the treatment of minimal hepatic encephalopathy: A network meta‐analysis involving 826 patients based on 10 randomized controlled trials

“…As ALC treatment was found without the presence of adverse reactions, it was verified to be effective, safe, and reliable . Furthermore, based on a randomized controlled trial conducted on the effects of rifaximin, probiotics, and LOLA on MHE, placebo, rifaximin, probiotics, and LOLA, ALC had the best efficacy in the treatment of MHE …”

Covert and Overt Hepatic Encephalopathy: Diagnosis and Management

“…It has been studied extensively with better results with its intravenous rather than oral formulation across the HE spectrum 79,80,81,82,83,84 .…”