Low-diversity microbiota and an increased metabolism of arginine and aromatic amino acids: a hallmark of hepatic encephalopathy in western Mexican patients with alcohol-associated cirrhosis.

AIMS: To evaluate the composition and functions of the gut microbiota in patients with decompensated alcohol-associated cirrhosis, with and without hepatic encephalopathy (HE). METHODS AND RESULTS: Faecal samples from 31 inpatients (20 with HE, 11 without HE), and from 18 age-balanced healthy controls (HC), were included. Microbial composition was determined by 16S rRNA amplicon sequencing and analysed using QIIME2. Metabolic pathways were inferred by PICRUSt2, and short-chain fatty acids (SCFAs) quantification was performed by gas chromatography. The gut microbiota of patients with HE was characterized by a diminished α-diversity, compared to no-HE (P < 0.01) and HC (P < 0.001) groups; ß-diversity also differed between HE vs no-HE patients (P < 0.05), and between HE vs HC (P < 0.001). In patients with HE, Escherichia/Shigella, Burkholderiales and Lactobacillales taxa predominated. In contrast, patients without HE were characterized by Veillonella and Bacteroides. Reduced levels of faecal SCFAs in both groups correlated with a depletion of beneficial taxa, such as Ruminococcus or Faecalibacterium. PICRUSt2 analysis showed both an enhanced catabolism of arginine through ammonia-producing pathways and chorismate biosynthesis in HE patients, a key precursor of aromatic amino acids. CONCLUSIONS: The gut microbiota of HE patients exhibits a proinflammatory dysbiotic profile, plus metabolic pathways that produce potentially neurotoxic byproducts.

Bacterial infections associated with hepatic encephalopathy: prevalence and outcome.

Hepatic encephalopathy (HE) is a major sign of severe liver disease and the impact of associated bacterial infections should be better evaluated. A retrospective cohort of 333 patients with cirrhosis and HE was analyzed in three periods of time, from 1984 to 1998. Variance analysis, Wilcoxon, Chi-square and Fisher's exact tests were used for statistical comparisons. Prevalence of bacterial infections decreased along the time (p = 0.0029). Spontaneous Bacterial Peritonitis -SBP- (37%) and urinary tract infection (30%) were the more frequent types of bacterial infections. Early death was significantly higher in HE with infection (46,47%) and the calculated RR was 2.047. Prognosis was worse in septicemia (79%) and respiratory tract infection (50%) and better in urinary tract infection (27%). SBP lethality was reduced from 70% to 38% (p = 0.062). In conclusion, lower prevalence of bacterial infections, in severe liver disease, was achieved in the last decade, but short-term prognosis remains bad, varying according to the type of bacterial infection.

The importance of bacterial infections as precipating factors of chronic hepatic encephalopathy in cirrhosis.

BACKGROUND/AIMS: It is generally accepted that chronic hepatic encephalopathy (HE) is a stable form of neuropsychiatric disorder, usually related to porto-systemic shunts and with no exogenous precipitating factors. Bacterial infections are frequent causes of morbidity in cirrhosis, including the development of HE in its acute form, but there are no reports of its role in chronic forms of HE. METHODOLOGY: We studied 168 episodes of hepatic encephalopathy in 111 patients with cirrhosis who were admitted to hospital during the last four years. Clinical staging was used for the diagnosis of acute and chronic HE, complemented by number connection tests and EEG. In chronic HE the diagnostic criteria were intolerance to animal proteins and a continuous need for medications and/or special diets. Alcohol was the etiology of cirrhosis in 81.1% of patients, hepatitis B or C virus in 12.6% and various factors in 6.3%. The male/female ratio was 3:1 and mean age was 53 years. RESULTS: Twenty patients (18%) were characterized as having chronic HE, whereas ninety-one (82%) presented acute HE. Precipitating factors could be detected in 43 out of 57 (75.4%) of chronic forms and in 108 of 111 (97.3%) episodes of acute HE. Bacterial infections were associated with HE in 15 of 43 cases (34.8%) of chronic HE and in 37 of 108 (34.7%) cases of acute HE (p < 0.05). Spontaneous bacterial peritonitis was the most prevalent infection in acute HE, whereas urinary tract infection was most frequent in chronic HE. Mortality was higher in acute than in chronic HE (p < 0.001), associated with Child C prognostic classification, grades III and IV of HE and more severe precipitating factors. CONCLUSIONS: The diagnosis and control of precipitating factors, especially bacterial infection, should also be considered during the treatment of chronic hepatic encephalopathy.

[Vegetable protein diets with or without non-absorbable antibiotics for the treatment of chronic portal systemic encephalopathy]. / Son necesarios los antibioticos inabsorbibles en pacientes con encefalopatía hepática manejados con dieta de proteínas vegetales?

Five patients with mild chronic portal systemic encephalopathy (PSE) were studied. The study was designed in a double cross over fashion in which each patient received during period I a 40 g vegetable protein diet as single treatment. During period II three g/day of oral kanamycin were added and then new periods of single vegetable protein diet (period III) and vegetable protein diet plus kanamycin (period IV) were introduced (identical to periods I and II respectively). Each period lasted two weeks. Several biweekly assessements-tests were determined including: mental state, asterixis grade, electroencephalograms, number connection tests, figure connection tests, blood ammonia levels and stool counts of total aerobes/anaerobes per g/feces were done. During the study none of the patients developed acute encephalopathy. In any case it was detected a significant improvement of the PSE parameters assessed with the addition of oral kanamycin. Fecal counts were very similar during the various periods of the study. We conclude that in mild portal systemic encephalopathy controlled with vegetable protein diet, the addition of non absorbable antibiotics is not mandatory for the management of these patients and may represent a potential risk of serious side effects. At the beginning of treatment vegetable protein diet should be administered and only in case of failure, antibiotics are to be indicated.