Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases. Invasion of the gut by oral bacteria in liver cirrhosis. Previous work has revealed an association between liver complications such as cirrhosis and the gut microbiome. Lanjuan Li and colleagues undertook a microbiome-wide association study of stool samples from 98 liver cirrhosis patients and 83 healthy controls. Quantitative metagenomics analysis revealed 75,245 genes that were significantly different in abundance between the two groups, many of which could be grouped into 66 clusters that represent cognate bacterial species. Of these, 28 species were enriched in liver cirrhosis patients and most were of buccal origin (mostly Veillonella and streptococci). The identified markers were unique liver cirrhosis-specific genes and the authors identify a set of just 15 of these genes that could form the basis of a highly accurate discrimination index that could be used as a diagnostic tool.

Alterations of the human gut microbiome in liver cirrhosis

EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis

http://demystifyingmedicine.od.nih.gov/DM15/m3d17/reading01.pdf

Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.27210

Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study Of Liver Diseases and the European Association for the Study of the Liver

https://www.cell.com/cancer-cell/pdf/S1535-6108(12)00072-4.pdf

Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4

Background Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. Methods In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. Results Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P = 0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events. Conclusions Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.)

/pdf/rifaximin-treatment-in-hepatic-encephalopathy-4nq6fjc3if.pdf

Kimberly Beavers

Papers

Rifaximin treatment in hepatic encephalopathy.