IL-6 Trans-Signaling Is Increased in Diabetes, Impacted by Glucolipotoxicity, and Associated With Liver Stiffness and Fibrosis in Fatty Liver Disease.

Many people living with diabetes also have nonalcoholic fatty liver disease (NAFLD). Interleukin-6 (IL-6) is involved in both diseases, interacting with both membrane-bound (classical) and circulating (trans-signaling) soluble receptors. We investigated whether secretion of IL-6 trans-signaling coreceptors are altered in NAFLD by diabetes and whether this might associate with the severity of fatty liver disease. Secretion patterns were investigated with use of human hepatocyte, stellate, and monocyte cell lines. Associations with liver pathology were investigated in two patient cohorts: 1) biopsy-confirmed steatohepatitis and 2) class 3 obesity. We found that exposure of stellate cells to high glucose and palmitate increased IL-6 and soluble gp130 (sgp130) secretion. In line with this, plasma sgp130 in both patient cohorts positively correlated with HbA1c, and subjects with diabetes had higher circulating levels of IL-6 and trans-signaling coreceptors. Plasma sgp130 strongly correlated with liver stiffness and was significantly increased in subjects with F4 fibrosis stage. Monocyte activation was associated with reduced sIL-6R secretion. These data suggest that hyperglycemia and hyperlipidemia can directly impact IL-6 trans-signaling and that this may be linked to enhanced severity of NAFLD in patients with concomitant diabetes. ARTICLE HIGHLIGHTS: IL-6 and its circulating coreceptor sgp130 are increased in people with fatty liver disease and steatohepatitis. High glucose and lipids stimulated IL-6 and sgp130 secretion from hepatic stellate cells. sgp130 levels correlated with HbA1c, and diabetes concurrent with steatohepatitis further increased circulating levels of all IL-6 trans-signaling mediators. Circulating sgp130 positively correlated with liver stiffness and hepatic fibrosis. Metabolic stress to liver associated with fatty liver disease might shift the balance of IL-6 classical versus trans-signaling, promoting liver fibrosis that is accelerated by diabetes.

Prevalence of Helicobacter pylori Infection in Bariatric Surgery Patients.

OBJECTIVE: To determine the rate of histology-proven Helicobacter pylori (HP) infection in patients undergoing bariatric surgery and to identify risk factors for HP infection. METHODS: In a retrospective analysis, patients who underwent bariatric surgery with gastric resection in a single hospital between January 2004 and January 2019 were analyzed. For each patient, a surgical specimen was submitted for anatomopathological examination and analyzed for gastritis or other anomalies. When gastritis was present, HP infection was confirmed by the identification of curvilinear bacilli in conventional histology or by specific immunohistochemical detection of HP antigen. RESULTS: A total of 6388 specimens were available for review (4365 women, 2023 men) with a mean age of 44.9 ± 11.2 years and a mean body mass index (BMI) of 49.3 ± 8.2 kg/m2. Histology-proven HP infection rate was 6.3% (n = 405). There was no significant difference in sex, BMI, and body weight between HP + and HP - patients. Logistic regressions identified age as a risk factor for HP infection in this population (OR 1.02, p < 0.0001, CI 95% 1.01-1.03 for every 1-year increase, OR 1.26, p < 0.0001, CI 95% 1.14-1.40 for every 10-year increase). CONCLUSIONS: The rate of histology-proven HP infection is low in patients with severe obesity who present for bariatric surgery and is associated with age.