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Summary: Background and Aims: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy‐proven cirrhosis in NAFLD. Methods: Adult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB‐4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort. Results: 147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95–0.97). FIB‐4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84–0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92–0.96), and FIB‐4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87–0.89). Conclusions: This cross‐sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and <65, unlikely to have cirrhosis so higher‐risk patients maintain access to specialty care. [ABSTRACT FROM AUTHOR]

Background: Adverse muscle composition (MC) as measured by magnetic resonance imaging has previously been linked to poor function, comorbidity, and increased hospitalization. The aim of this study was to investigate if adverse MC predicts all‐cause mortality using data from UK Biobank. Methods: There were 40 178 participants scanned using a 6 min magnetic resonance imaging protocol. Images were analysed for thigh fat‐tissue free muscle volume and muscle fat infiltration (MFI) using AMRA® Researcher (AMRA Medical, Linköping, Sweden). For each participant, a sex, weight, and height invariant muscle volume z‐score was calculated. Participants were partitioned into four MC groups: (i) normal MC, (ii) only low muscle volume [<25th percentile for muscle volume z‐score (population wide)], (iii) only high MFI [>75th percentile (population wide, sex‐specific)], and (iv) adverse MC (low muscle volume z‐score and high MFI). Association of MC groups with mortality was investigated using Cox proportional‐hazard modelling with normal MC as referent (unadjusted and adjusted for low hand grip strength, sex, age, body mass index, previous diagnosis of disease (cancer, type 2 diabetes and coronary heart disease), lifestyle, and socioeconomic factors (smoking, alcohol consumption, physical activity, and Townsend deprivation index). Results: Muscle composition measurements were complete for 39 804 participants [52% female, mean (SD) age 64.2 (7.6) years and body mass index 26.4 (4.4) kg/m2]. Three hundred twenty‐eight deaths were recorded during a follow‐up period of 2.9 (1.4) years after imaging. At imaging, adverse MC was detected in 10.5% of participants. The risk of death from any cause in adverse MC compared with normal MC was 3.71 (95% confidence interval 2.81–4.91, P < 0.001). Only low muscle volume and only high MFI were independently associated with all‐cause mortality [1.58 (1.13–2.21), P = 0.007, and 2.02 (1.51–2.71), P < 0.001, respectively]. Adjustment of low hand grip strength [1.77 (1.28–2.44), P < 0.001] did not attenuate the associations with any of the MC groups. In the fully adjusted model, adverse MC and only high MFI remained significant (P < 0.001 and P = 0.020) while the association with only low muscle volume was attenuated to non‐significance (P = 0.560). The predictive performance of adverse MC [1.96 (1.42–2.71), P < 0.001] was comparable with that of previous cancer diagnosis [1.93 (1.47–2.53), P < 0.001] and smoking [1.71 (1.02–2.84), P = 0.040]. Low hand grip strength was borderline non‐significant [1.34 (0.96–1.88), P = 0.090]. Conclusions: Adverse MC was a strong and independent predictor of all‐cause mortality. Sarcopenia guidelines can be strengthened by including cut‐offs for myosteatosis enabling detection of adverse MC. [ABSTRACT FROM AUTHOR]

BACKGROUNDHepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cognition. However, microbial functional changes are unclear. The aim of this study was to determine the effect of FMT on the gut-brain axis compared with placebo, using microbial function based on bile acids (BAs), inflammation (serum IL-6, LPS-binding protein [LBP]), and their association with EncephalApp.METHODSTwenty cirrhotic patients were randomized 1:1 into groups that received 1-time FMT capsules from a donor enriched in Lachnospiraceae and Ruminococcaceae or placebo capsules, with 5-month follow-up for safety outcomes. Stool microbiota and BA; serum IL-6, BA, and LBP; and EncephalApp were analyzed at baseline and 4 weeks after FMT/placebo. Correlation networks among microbiota, BAs, EncephalApp, IL-6, and LBP were performed before/after FMT.RESULTSFMT-assigned participants had 1 HE recurrence and 2 unrelated infections. Six placebo-assigned participants developed negative outcomes. FMT, but not placebo, was associated with reduced serum IL-6 and LBP and improved EncephalApp. FMT-assigned participants demonstrated higher deconjugation and secondary BA formation in feces and serum compared with baseline. No change was seen in placebo. Correlation networks showed greater complexity after FMT compared with baseline. Beneficial taxa, such as Ruminococcaceae, Verrucomicrobiaceae, and Lachnospiraceae, were correlated with cognitive improvement and decrease in inflammation after FMT. Fecal/serum secondary/primary ratios and PiCRUST secondary BA pathways did not increase in participants who developed poor outcomes.CONCLUSIONGut microbial function in cirrhosis is beneficially affected by capsular FMT, with improved inflammation and cognition. Lower secondary BAs in FMT recipients could select for participants who develop negative outcomes.TRIAL REGISTRATIONClinicaltrials.gov NCT03152188.FUNDINGNational Center for Advancing Translational Sciences NIH grant R21TR002024, VA Merit Review grant 2I0CX001076, the United Kingdom National Institute for Health Research Biomedical Facility at Imperial College London, the British Heart Foundation, Wellcome Trust, and King's College London.