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.
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.
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).
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.
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.
Morbid obesity (body mass index [BMI] ≥40 kg/m2) is a relative contraindication to liver transplantation (LT) at many transplant centers. The safety and efficacy of pre-LT bariatric surgery in morbidly obese LT candidates is unknown. Herein, we describe a cohort study of morbidly obese LT candidates who failed to achieve adequate weight loss through a medically supervised weight loss program and subsequently underwent sleeve gastrectomy (SG) at our institution. In total, 32 LT candidates with a median Model for End-Stage Liver Disease (MELD) score of 12 (interquartile range [IQR], 10–13) underwent SG. All LT candidates had a history of hepatic decompensation, but complications of liver disease were required to be well controlled at the time of SG. Median pre-SG BMI was 45.0 kg/m2 (IQR, 42.1–49.0 kg/m2). There were no perioperative deaths or liver-related morbidity. One patient experienced major perioperative morbidity secondary to a gastric leak, which was managed nonoperatively. Median weight loss at 6 and 12 months after SG was 22.0 kg (IQR, 18.9–26.8 kg) and 31.0 kg (IQR, 23.6–50.3 kg), respectively, corresponding to a percentage of excess body weight lost of 33.4% and 52.4%. Within 6 months after SG, 28 (88%) candidates were deemed eligible for LT. Our center’s experience highlights the potential option of SG in morbidly obese LT candidates with advanced liver disease who might otherwise be excluded from pursuing LT.
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.
The gut microbiome, the multispecies community of microbes that exists in the gastrointestinal tract, encodes several orders of magnitude more functional genes than the human genome. It also plays a pivotal role in human health, in part due to metabolism of environmental, dietary, and host‐derived substrates, which produce bioactive metabolites. Perturbations to the composition and associated metabolic output of the gut microbiome have been associated with a number of chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). Here, we review the rapidly evolving suite of next‐generation techniques used for studying gut microbiome composition, functional gene content, and bioactive products and discuss relationships with the pathogenesis of NAFLD.
Hospitalization for ulcerative colitis is a high-risk period associated with increased risk of Clostridium difficile infection, thromboembolism, and opiate use. The study aim was to develop and implement a quality-improvement intervention for inpatient ulcerative colitis management that standardizes gastroenterology consultant recommendations and improves delivery of evidence-based care.
All adult patients hospitalized for ulcerative colitis between July 1, 2014, and December 31, 2017, who received intravenous corticosteroids were included. On July 1, 2016, the UCSF Inpatient Ulcerative Colitis Protocol was implemented, featuring standardized core recommendations and a daily checklist for gastroenterology consultant notes, a bundled IBD electronic order set, and an opiate awareness campaign. The composite primary outcome was adherence to all 3 evidence-based care metrics: C. difficile testing performed, pharmacologic venous thromboembolism (VTE) prophylaxis ordered, and opiates avoided.
Ninety-three ulcerative colitis hospitalizations occurred, including 36 preintervention and 57 postintervention. Age, gender, disease duration, disease extent, and medication use were similar preintervention and postintervention. C. difficile testing was performed in 100% of hospitalizations. Venous thromboembolism prophylaxis was ordered on 84% of hospital days before intervention compared with 100% after intervention (P ≤ 0.001). Opiates were administered in 67% of preintervention hospitalizations, compared with 53% of postintervention hospitalizations (P = 0.18). The median daily dose of oral morphine equivalents decreased from 12.1 mg before intervention to 0.5 mg after intervention (P = 0.02). The composite outcome of adherence to all 3 metrics was higher after intervention (25% vs. 47%, P = 0.03).
Evidence-based inpatient ulcerative colitis management may be optimized with standardized algorithms that reinforce core principles, reduce care variation, and do not require IBD specialists to implement.
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