Utilising Pancreatic Exocrine Insufficiency in the Detection of Resectable Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed late, leading to a high mortality rate. Early detection facilitates better treatment options. The aim of this UK-based case-control study was to determine whether two validated tests for pancreatic exocrine insufficiency (PEI), namely, the 13C-mixed triglyceride breath test (13C-MTGBT) and a faecal elastase (FE-1) test, can discriminate between patients with resectable PDAC versus healthy volunteers (HVs) along with a comparison group with chronic pancreatitis (CP). Discrimination between disease states and HVs was tested with receiver operator characteristic (ROC) curves. In total, 59 participants (23 PDAC (16 men), 24 HVs (13 men) and 12 CP (10 men)) were recruited, with a similar age in each population, and a combined median (IQR) age of 66 (57-71). The areas under the ROC curve for discriminating between PDAC and HVs were 0.83 (95% CI: 0.70-0.96) for the 13C-MTGBT, and 0.85 (95% CI: 0.75-0.95) for the FE-1 test. These were similar to CP vs. HV. In conclusion, PEI occurs in resectable PDAC to a similar extent as in CP; further large-scale, prospective studies using these tests in the primary care setting on high-risk groups are warranted.

Factors independently associated with cardiorespiratory fitness in patients with non-alcoholic fatty liver disease.

Low cardiorespiratory fitness (CRF) is associated with non-alcoholic fatty liver disease (NAFLD) and low CRF is an important risk factor for cardiovascular disease. The factors that influence CRF in NAFLD are poorly understood and it has been suggested that reduced hepatic mitochondrial function (HMF) may be linked to low CRF. Therefore, our aim was to determine the factors associated with CRF in NAFLD. METHODS: Ninety-seven patients with NAFLD were studied. CRF was assessed by treadmill testing and expressed as maximal O2 consumption (VO2 peak) per lean body mass. HMF was assessed by the 13 C-ketoisocaproate breath test. Multivariable linear regression modelling was undertaken to test the independence of associations with CRF. RESULTS: Mean (SD) age was 51 (13) years and 61% were men. With CRF as the outcome, age (B coefficient -0.3, 95%CI -0.4, -0.2, P < .0001), total body fat mass (B coefficient -0.2, 95%CI -0.3, -0.05, P = .01), type 2 diabetes mellitus (T2DM) (B coefficient -3.6, 95%CI -1.1, -6.1, P = .005), smoking status (B coefficient -5.7, 95%CI -1.9, -9.5, P = .004), serum γ-glutamyl transferase (GGT) (B coefficient -0.04, 95%CI -0.05, -0.02, P < .0001), HMF (B coefficient -0.5, 95%CI -0.8, -0.1, P = .01) and diastolic function (B coefficient 0.1, 95%CI 0.05, 0.13, P < .0001) were independently associated with CRF. This model explained 60% of the total variance in CRF (R2  = 0.6, P < .0001); and this model with GGT alone explained 24% of the variance in CRF. CONCLUSIONS: In patients with NAFLD, HMF is independently associated with CRF and a model with GGT alone explained most of the variance in CRF.

Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD. METHODS: We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8 ± 12.6 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies lactis BB-12; n = 55) or placebo (n = 49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy, and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study, the fecal microbiome were analyzed by 16S ribosomal DNA sequencing. RESULTS: Mean baseline and end-of-study magnetic resonance spectroscopy liver fat percentage values were 32.3% ± 24.8% and 28.5% ± 20.1% in the synbiotic group and 31.3% ± 22% and 25.2% ± 17.2% in the placebo group. In the unadjusted intention-to-treat analysis, we found no significant difference in liver fat reduction between groups (ß = 2.8; 95% confidence interval, -2.2 to 7.8; P = .30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (ß = 2; 95% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis. CONCLUSIONS: In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, Number: NCT01680640).

The characterisation of hepatic mitochondrial function in patients with non-alcoholic fatty liver disease (NAFLD) using the 13C-ketoisocaproate breath test.

Hepatic mitochondrial function (HMF) assessed by the 13C-ketoisocaproate breath test (13C-KICA BT) has been previously shown to be significantly associated with the severity of biopsy proven non-alcoholic fatty liver disease (NAFLD). However, it is uncertain whether any perturbation in HMF relates specifically to severity of liver disease or factors associated with metabolic syndrome within (NAFLD). Our aim was to investigate whether there was any change in HMF assessed by 13C-KICA BT in patients with NAFLD compared to control subjects, and to assess the factors that are independently associated with HMF. METHODS: 77 patients with NAFLD and 11 healthy control subjects were studied. HMF was assessed using 13C-KICA BT and expressed as cumulative % 13C-dose recovered on breath over 1 h (cPDR over 1 h). Liver fat and fibrosis was assessed by transient elastography. Multivariable linear regression modelling was undertaken to test the independence of associations with HMF. RESULTS: HMF (cPDR over 1 h) was lower in NAFLD compared to controls [13.4% (4.8) v. 21.0% (6.3); p < 0.0001)]. In NAFLD, HMF was lower in patients with diabetes versus no diabetes [12.7% (3.4) v. 14.3% (6.1); p = 0.003)]. Regression modelling showed age (ß = -0.08; p = 0.01), waist circumference (ß = -0.08; p = 0.01), hip circumference (ß = -0.04; p = 0.01), aspartate aminotransferase (AST) (ß = -0.05; p = 0.01) and diabetes status (ß = -1.81; p = 0.01) were independently associated with HMF (R2 = 41.5%; p < 0.0001). CONCLUSIONS: In patients with NAFLD (compared to healthy subjects), there was a reduction in HMF assessed by the 13C-KICA BT. Furthermore, in patients with NAFLD, HMF is independent and inversely associated with age, waist and hip circumference, AST and diabetes status.