The gut microbiome, a diverse microbial community in the gastrointestinal tract, plays a pivotal role in the maintenance of health. The gut microbiome metabolizes dietary and host-derived molecules to produce bioactive metabolites, which have a wide array of effects on host metabolism and immunity. 'Dysbiosis' of the gut microbiome, commonly considered as perturbation of microbiome diversity and composition, has been associated with intestinal and extra-intestinal diseases, including nonalcoholic fatty liver disease (NAFLD). A number of endogenous and exogenous factors, such as nutritional intake and xenobiotic exposure, can alter the gut microbiome. We will review the evolving methods for studying the gut microbiome and how these profiling techniques have been utilized to further our understanding of the gut microbial community composition and functional potential in the clinical spectrum of NAFLD. We will highlight microbiome-host interactions that may contribute to the pathogenesis of NAFLD, with a primary focus on mechanisms related to the metabolic output of the gut microbiome. Finally, we will discuss potential therapeutic implications of the gut microbiome in NAFLD.

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Background The proportion of older patients awaiting liver transplantation (LT) is rising. While increased age and LT-MELD are known to increase the risk of graft loss, no studies have explored whether there is a synergistic effect between LT-age and LT-MELD. Methods All US adult, non-Status 1 recipients of primary deceased donor LT from 2/05–1/10 without MELD exceptions were included (n=15,677). Recipients were categorized by LT-age [18–59y (n=11,966), 60–64y (n=2,181), 65–69y (n=1,177), ≥70y (n=343)] and LT-MELD [low (<20, n=5,290), mid (20–27, n=5,112), high (≥28, n=5,265)]. Adjusted Cox models evaluated the 1) independent and 2) combined effects of LT-age and LT-MELD on graft loss (death or re-LT). Results LT-age ≥70y (HR=1.65, 95% CI 1.08–1.82) and LT-MELD ≥28 (HR=1.46, 95% CI 1.02–1.47) were independently associated with increased risk of graft loss (p<0.001). In a model allowing for the interaction between LT-age and LT-MELD, the risk of graft loss for recipients ≥70y with MELD ≥28 was higher than predicted by the additive model (HR=2.38, 95%CI 1.73–3.27, p<0.001) resulting in one-year graft survival of 56%. However, the increased risk of graft loss in recipients ≥70y was attenuated at lower LT-MELD <28. Furthermore, the interaction term was not significant for any other LT-age and LT-MELD combination. Conclusion Our analyses suggest that recipients should not be excluded solely based on age, however LT for recipients ≥70y at high LT-MELD scores should be undertaken cautiously.

Significant volume reductions of brain metastases measured at either 6 or 12 weeks post-SRS were strongly associated with prolonged local control. Furthermore, early volume reduction was associated with less corticosteroid use and stable neurological symptoms.

Background and Aims: Patients with NAFLD with significant hepatic fibrosis (Stage ≥ 2) are at increased risk of liver-related morbidity and are candidates for pharmacologic therapies. In this study, we compared the diagnostic accuracy of MEFIB (the combination of magnetic resonance elastography [MRE] and ) and FAST (FibroScan-aspartate aminotransferase; combined liver stiffness measurement by vibration-controlled transient elastography, controlled attenuation parameter, and aspartate aminotransferase) for detecting significant fibrosis.