Anti-GCA monoclonal antibody, clone 3G6

Background Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non-alcoholic fatty liver disease (NAFLD). We investigated the associations between serum and faecal BAs, gut microbiome and fibrosis in patients with and without NAFLD and examined the impact of diet and alcohol consumption on these relationships. Methods Adult patients (n = 122) underwent liver biopsy and BAs characterization by high-performance liquid chromatography/mass spectrometry. Gut microbiome composition was analysed using next-generation 16S rRNA sequencing. Diet and alcohol intake were determined by 3-day food diary. Results Serum and faecal BA concentrations increased progressively among non-NAFLD controls (n = 55), NAFLD patients with no/mild fibrosis (F0-2, n = 58) and NAFLD with advanced fibrosis (F3/4, n = 9). Progressive increases in serum BAs were driven by primary conjugated BAs including glycocholic acid [GCA] and secondary conjugated BAs. In contrast, faecal BA increase was driven by secondary unconjugated BAs (predominately deoxycholic acid [DCA]). Serum GCA levels and faecal DCA levels correlated with the abundance of Bacteroidaceae and Lachnospiraceae, and stool secondary BAs with an unclassifiable family of the order Bacteroidales (Bacteroidales;other). These bacterial taxa were also associated with advanced fibrosis. Modest alcohol consumption was positively correlated with faecal DCA levels and relative abundance of Lachnospiracaea and Bacteroidales;other. Conclusions Higher serum and faecal BA levels are associated with advanced fibrosis in NAFLD. Specific gut bacteria link alterations in BA profiles and advanced fibrosis, and may be influenced by low-level alcohol consumption.

Introduction The purpose of our study was to compare visual rating and volumetry of brain atrophy in an elderly population over a 5-year period and compare findings with cognitive test results. Materials and Methods Two hundred and one subjects were examined with magnetic resonance imaging (MRI) of the brain. Visual rating and volumetry were performed in all subjects at ages 75 and 80. Cognitive function at both time points was assessed with the Mini-Mental State Examination (MMSE) and Trail Making Tests A and B (TMT-A and TMT-B). Changes in visual rating and volumetry were compared with changes in cognitive test. Results A correlation was found between visual rating of medial temporal lobe atrophy (MTA) and hippocampal volumetry at both time points (rs = -.42 and rs = -.49, p < .001, respectively). The correlation between visual rating of posterior atrophy (PA); frontal atrophy (F-GCA) and volumetry of these brain regions was significant only at age 80 (rs = -.16, p = .02 for PA and rpb = .19, p = .006 for F-GCA). Visual rating showed only a minimal progression of regional atrophy at age 80, whereas volumetry showed 2%-5% decrease in volume depending on brain region. Performance in the MMSE, TMT-A, and TMT-B was virtually unchanged between ages 75 and 80. Conclusion We found a mild age-associated decrease in regional brain volumes in this healthy cohort with well-preserved cognitive functions. Visual assessment may not be sufficient for detecting mild progression of brain atrophy due to normal aging, whereas volumetry is more sensitive to capture these subtle changes.