Published online Mar 27, 2022. doi: 10.4254/wjh.v14.i3.634
Peer-review started: March 31, 2021
First decision: July 27, 2021
Revised: August 1, 2021
Accepted: February 22, 2022
Article in press: February 22, 2022
Published online: March 27, 2022
Processing time: 357 Days and 17.1 Hours
Hepatic encephalopathy (HE) can be considered a result of dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by "gut-centric" therapies, such as the administration of nonabsorbable disaccharides, nonabsorbable antibiotics, probiotics and prebiotics.
The HE treatment of choice is non-absorbable disaccharides, such as lactulose and lactitol. Non-absorbable disaccharides like lactulose are associated with non-serious (mainly gastrointestinal) adverse events like diarrhea and bloating, hence, due to the side effect profile, newer drugs continue to be tested for treatment of HE. Rifaximin is an antibiotic which modulating effect on the composition of the intestinal flora partly explains the clinical efficacy in reducing endotoxaemia and inflammatory markers that contribute to HE progression. Probiotics are effective in the treatment of minimal hepatic encephalopathy. Various studies have shown some improvement in either the prevalence of minimal hepatic encephalopathy or results in neuropsychological tests with the use of probiotics.
To assess the short-term efficacy and safety of the probiotic Escherichia coli Nissle 1917 (EcN) strain compared to lactulose and rifaximin in patients with minimal/mild HE.
In total, 45 patients with HE were enrolled in this prospective, single-centre, open-label, randomized study. Participants were randomly assigned at a ratio of 1:1:1 to one of the treatment groups: the EcN group (n = 15), lactulose group (n = 15) or rifaximin group (n = 15) for a 1 mo intervention period. The main primary outcomes of the study were changes in serum ammonia and Stroop test score. The secondary outcomes were markers of a chronic systemic inflammatory response (ІL-6, ІL-8, and IFN-γ) and bacteriology of the stool flora evaluated by specialized nonculture techniques after a 1 mo intervention period.
Rifaximin or EcN showed a more significant reduction in serum ammonia and normalization of Bifidobacteria and Lactobacilli abundance compared to the lactulose group. In the primary outcome analysis, improvements in the Stroop test parameters in all intervention groups were observed. Moreover, EcN-treated patients performed 15% faster on the Stroop test than the lactulose group patients (P = 0.017). Both EcN and rifaximin produced similar significant reductions in the proinflammatory cytokines INF-γ, IL-6 and IL-8.
Probiotic EcN strain was safe and quite efficient for HE treatment. The probiotic reduced the ammonia content and the level of serum proinflammatory cytokines, normalized the gut microbiota composition and improved the cognitive function of patients with HE. The application of the EcN strain was more effective than lactulose treatment.
New research on the beneficial effects of gut microbiota modulation and related mechanisms of their interaction with liver disease should be conducted to target better a wide variety of probiotic strains. Moreover, one of the possible gut microbiota-based interventions that may be claimed in the nearest future is fecal microbiota transplantation.