Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis.

Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.

Altered gut microbiota is associated with sleep disturbances in patients with minimal hepatic encephalopathy caused by hepatitis B-related liver cirrhosis.

BACKGROUND: Sleep disturbances are prevalent in patients with minimal hepatic encephalopathy (MHE). This study aimed to evaluate the association between sleep disturbances and altered gut microbiota in patients with MHE caused by hepatitis B-related liver cirrhosis. RESEARCH DESIGN AND METHODS: Ninety-eight and 45 patients with MHE were included in exploration and validation cohorts, respectively. Sleep disturbances were assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Microbiota in fecal samples were analyzed via amplicon sequencing of bacterial 16S ribosomal RNA genes. RESULTS: The gut microbiomes of MHE patients with sleep disturbances were characterized by lower bacterial diversity and distinct bacterial composition. Relative abundances of Streptococcus salivarius and Veillonella were independent predictors of sleep disturbances in MHE patients and well-distinguished MHE patients with and without sleep disturbances in both the exploration and validation cohorts. Moreover, the relative abundances of S. salivarius were positively correlated with plasma ammonia levels, and functional modules associated with protein digestion and absorption and lipopolysaccharide biosynthesis were enriched in the microbiomes of MHE patients with sleep disturbances. CONCLUSIONS: Both S. salivarius and Veillonella were associated with sleep disturbances in patients with MHE caused by hepatitis B-related liver cirrhosis.

EncephalApp stroop test versus electronic number connection test-A for screening minimal hepatic encephalopathy in patients with liver cirrhosis: a comparative study.

OBJECTIVES: Minimal hepatic encephalopathy (MHE) is a common neuropsychiatric complication of liver cirrhosis. Both EncephalApp Stroop test (EncephalApp) and electronic number connection test-A (eNCT-A) are novel computerised psychometric tests for MHE screening. We aimed to compare the efficiency, convenience, accessibility, and acceptability of EncephalApp with that of eNCT-A for MHE screening in cirrhotic patients. METHODS: Ninety-five patients with hepatitis B-induced liver cirrhosis were included and respectively tested by the psychometric hepatic encephalopathy score (PHES), EncephalApp, and eNCT-A. Using PHES as the gold standard for MHE diagnosis, the efficiency of EncephalApp and eNCT-A for MHE screening were respectively analysed by the receiver operating characteristic (ROC) curve, and the areas under the ROC curve (AUROC) were compared. The convenience, accessibility, and acceptability of PHES, EncephalApp and eNCT-A were respectively evaluated by the 5-point Likert scale. RESULTS: Fifty-two (55%) of included cirrhotic patients were diagnosed with MHE. The EncephalApp had a sensitivity of 84.6%, a specificity of 74.4%, and an AUROC of 0.836. Meanwhile, the eNCT-A had a sensitivity of 78.8%, a specificity of 83.7%, and an AUROC of 0.845. No significant difference in AUROC was detected between the EncephalApp and eNCT-A (p = .453). Compared with the EncephalApp, the eNCT-A presented better convenience and higher acceptability in cirrhotic patients undergoing MHE screening (p = .019 and p < .001, respectively). CONCLUSIONS: As with the EncephalApp, the eNCT-A will be a potential home monitoring and point-of-care tool for cirrhotic patients at high risk of MHE.