Dysbiosis of the Duodenal Mucosal Microbiota Is Associated With Increased Small Intestinal Permeability in Chronic Liver Disease OBJECTIVES: Chronic liver disease (CLD) is associated with both alterations of the stool microbiota and increased small intestinal permeability. However, little is known about the role of the small intestinal mucosa-associated microbiota (MAM) in CLD. The aim of this study was to evaluate the relationship between the duodenal MAM and both small intestinal permeability and liver disease severity in CLD. METHODS: Subjects with CLD and a disease-free control group undergoing routine endoscopy underwent duodenal biopsy to assess duodenal MAM by 16S rRNA gene sequencing. Small intestinal permeability was assessed by a dual sugar (lactulose: rhamnose) assay. Other assessments included transient elastography, endotoxemia, serum markers of hepatic inflammation, dietary intake, and anthropometric measurements. RESULTS: Forty-six subjects (35 with CLD and 11 controls) were assessed. In subjects with CLD, the composition (P = 0.02) and diversity (P < 0.01) of the duodenal MAM differed to controls. Constrained multivariate analysis and linear discriminate effect size showed this was due to Streptococcus-affiliated lineages. Small intestinal permeability was significantly higher in CLD subjects compared to controls. In CLD, there were inverse correlations between microbial diversity and both increased small intestinal permeability (r = −0.41, P = 0.02) and serum alanine aminotransferase (r = −0.35, P = 0.04). Hepatic stiffness was not associated with the MAM. DISCUSSION: In CLD, there is dysbiosis of the duodenal MAM and an inverse correlation between microbial diversity and small intestinal permeability. TRANSLATIONAL IMPACT: Strategies to ameliorate duodenal MAM dysbiosis may ameliorate intestinal barrier dysfunction and liver injury in CLD.

Selection Between Liver Resection Versus Transarterial Chemoembolization in Hepatocellular Carcinoma: A Multicenter Study OBJECTIVES: Models should be developed to assist choice between liver resection (LR) and transarterial chemoembolization (TACE) for hepatocellular carcinoma. METHODS: After separating 520 cases from 5 hospitals into training (n = 302) and validation (n = 218) data sets, we weighted the cases to control baseline difference and ensured the causal effect between treatments (LR and TACE) and estimated progression-free survival (PFS) difference. A noninvasive PFS model was constructed with clinical factors, radiological characteristics, and radiomic features. We compared our model with other 4 state-of-the-art models. Finally, patients were classified into subgroups with and without significant PFS difference between treatments. RESULTS: Our model included treatments, age, sex, modified Barcelona Clinic Liver Cancer stage, fusion lesions, hepatocellular carcinoma capsule, and 3 radiomic features, with good discrimination and calibrations (area under the curve for 3-year PFS was 0.80 in the training data set and 0.75 in the validation data set; similar results were achieved in 1- and 2-year PFS). The model had better accuracy than the other 4 models. A nomogram was built, with different scores assigned for LR and TACE. Separated by the threshold of score difference between treatments, for some patients, LR provided longer PFS and might be the better option (training: hazard ratio [HR] = 0.50, P = 0.014; validation: HR = 0.52, P = 0.026); in the others, LR provided similar PFS with TACE (training: HR = 0.84, P = 0.388; validation: HR = 1.14, P = 0.614). TACE may be better because it was less invasive. DISCUSSION: We propose an individualized model predicting PFS difference between LR and TACE to assist in the optimal treatment choice.

Characterization of Proximal Small Intestinal Microbiota in Patients With Suspected Small Intestinal Bacterial Overgrowth: A Cross-Sectional Study OBJECTIVES: The composition of the small intestinal microbiota has not yet been characterized thoroughly using culture-independent techniques. We compared small intestinal microbial communities in patients with and without small intestinal bacterial overgrowth (SIBO) using culture-dependent and culture-independent bacterial identification approaches. METHODS: Small bowel aspirate and mucosal samples were collected from patients with suspected SIBO. The aspirates were cultured to diagnose SIBO, defined as ≥104 colony-forming units/mL coliform or ≥105 colony-forming units/mL upper aerodigestive tract bacteria. Bacteria in the aspirates and mucosa were identified using 16S rRNA gene sequencing. We compared small intestinal microbiome composition between groups with and without a culture-based SIBO diagnosis. RESULTS: Analysis of the aspirate and mucosal microbial communities from 36 patients revealed decreased α-diversity but no differences in β-diversity in patients with SIBO compared with those without SIBO. There were no significant differences in the relative abundance of individual taxa from the aspirates or mucosa after adjustment for false discovery rate between patients with and without SIBO. Subgroup analysis revealed significant differences in mucosal β-diversity between the coliform and upper aerodigestive tract subgroups. Relative abundances of a mucosal Clostridium spp. (P = 0.05) and an aspirate Granulicatella spp. (P = 0.02) were higher in coliform SIBO vs non-SIBO subgroups. The microbial composition and relative abundance of multiple taxa significantly differed in the mucosal and aspirate specimens. DISCUSSION: Culture-based results of small bowel aspirates do not correspond to aspirate microbiota composition but may be associated with species richness of the mucosal microbiota.

Multicenter Validation Study of a Diagnostic Algorithm to Detect NASH and Fibrosis in NAFLD Patients With Low NAFLD Fibrosis Score or Liver Stiffness OBJECTIVES: Nonalcoholic steatohepatitis (NASH) and fibrosis play critical roles for the prognosis of patients with nonalcoholic fatty liver disease (NAFLD). Identification of patients at risk of NASH and fibrosis is therefore critical for disease management. NAFLD Fibrosis Score (NFS) and transient elastography (TE) have been suggested to exclude advanced fibrosis. However, there is increasing evidence that also patients with NASH and early fibrosis are at risk of disease progression and complications, emphasizing the need for improved noninvasive risk stratification in NAFLD. METHODS: Because hepatocyte apoptosis plays an early role in NASH pathogenesis, we evaluated whether the apoptosis biomarker M30 might identify NAFLD patients who are at risk of NASH and fibrosis despite low NFS or TE values. Serum M30 levels were assessed by enzyme-linked immunosorbent assay in combination with NFS and/or TE in an exploration (n = 103) and validation (n = 100) cohort of patients with biopsy-proven NAFLD. RESULTS: Most patients with low NFS (cutoff value < −1.455) revealed increased M30 levels (>200 U/L) in the exploration (62%) and validation (67%) cohort, and more than 70% of them had NASH, mostly with histological fibrosis. Vice versa, most patients with NFS < −1.455 but nonelevated M30 levels showed no NASH. NASH was also detected in most patients with indeterminate NFS (−1.455 to 0.676) but elevated M30 levels, from which ∼90% showed fibrosis. Similar results were obtained when using TE instead of NFS. DISCUSSION: The combination of the M30 biomarker with NFS or TE enables a more reliable identification of patients with an increased risk of progressed NAFLD and improves patient stratification.