The interplay between western diet and gut microbiota drives the development of non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. However, the specific microbial and metabolic mediators contributing to non-alcoholic steatohepatitis remain to be identified. Here, a choline-low high-fat and high-sugar diet, representing a typical western diet, named CL-HFS, successfully induces male mouse non-alcoholic steatohepatitis with some features of the human disease, such as hepatic inflammation, steatosis, and fibrosis. Metataxonomic and metabolomic studies identify Blautia producta and 2-oleoylglycerol as clinically relevant bacterial and metabolic mediators contributing to CL-HFS-induced non-alcoholic steatohepatitis. In vivo studies validate that both Blautia producta and 2-oleoylglycerol promote liver inflammation and hepatic fibrosis in normal diet- or CL-HFS-fed mice. Cellular and molecular studies reveal that the GPR119/TAK1/NF-κB/TGF-β1 signaling pathway mediates 2-oleoylglycerol-induced macrophage priming and subsequent hepatic stellate cell activation. These findings advance our understanding of non-alcoholic steatohepatitis pathogenesis and provide targets for developing microbiome/metabolite-based therapeutic strategies against non-alcoholic steatohepatitis.

Serum β-hydroxybutyrate (β-HB) is frequently utilized as a surrogate marker for hepatic fatty acid oxidation; however, few studies have investigated this relationship during states of liver disease. We found that the progression of nonalcoholic fatty liver disease (NAFLD) is associated with reductions in circulating β-HB and liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). As well, decreased rates of hepatic fatty acid oxidation correlated with liver HMGCS2 mRNA and serum β-HB. Our work supports serum β-HB as a potential marker for hepatic fatty acid oxidation and liver injury during NAFLD.

Patients with morbid obesity are at high risk for nonalcoholic fatty liver disease (NAFLD) complicated by liver fibrosis. The clinical utility of transient elastography (TE) by Fibroscan in patients with morbid obesity (body mass index (BMI) ≥ 40 kg/m²) is not well-defined. We examined the diagnostic accuracy of Fibroscan in predicting significant liver fibrosis (fibrosis stage ≥2) in morbidly obese patients (BMI ≥ 40 kg/m²). Patients scheduled for bariatric surgery were prospectively enrolled. Intraoperative liver biopsy, liver-stiffness measurement (LSM) by Fibroscan (XL probe), and biochemical evaluation were all performed on the same day. The endpoint was significant liver fibrosis defined as fibrosis stage ≥2 based on the Nonalcoholic Steatohepatitis Clinical Research Network. The optimal LSM cutoff value for detecting significant fibrosis was determined by using the Youden Index method. Routine clinical, laboratory, and elastography data were analyzed by stepwise logistic regression analysis to identify predictors of significant liver fibrosis and build a predictive model. An optimal cutoff point of the new model’s regression formula for predicting significant fibrosis was determined by using the Youden index method. One hundred sixty-seven patients (mean age, 46.4 years) were included, of whom 83.2% were female. Histological assessment revealed the prevalence of steatohepatitis and significant fibrosis of 40.7% and 11.4%, respectively. The median LSM was found to be significantly higher in the significant fibrosis group compared to those in the no or non-significant fibrosis group (18.2 vs. 7.7 kPa, respectively; p = 0.0004). The optimal LSM cutoff for predicting significant fibrosis was 12.8 kPa, with an accuracy of 71.3%, sensitivity of 73.7%, specificity of 70.9%, positive predictive value of 24.6%, negative predictive value of 95.5%, and ROC area of 0.723 (95% CI: 0.62–0.83). Logistic regression analysis identified three independent predictors of significant fibrosis: LSM, hemoglobin A1c, and alkaline phosphatase. A risk score was developed by using these three variables. At an optimal cutoff value of the regression formula, the risk score had an accuracy of 79.6% for predicting significant fibrosis, sensitivity of 89.5%, specificity of 78.4%, positive predictive value of 34.7%, negative predictive value of 98.3%, and ROC area of 0.855 (95% CI: 0.76–0.95). Fibroscan utility in predicting significant liver fibrosis in morbidly obese subjects is limited with accuracy of 71.3%. A model incorporating hemoglobin A1c and alkaline phosphatase with LSM improves accuracy in detecting significant fibrosis in this patient population.

To describe our results of laparoscopic transperitoneal division of the hernia sac with purse string closure of the proximal peritoneum for inguinal hernia repair in children. A retrospective case review of all patients undergoing laparoscopic herniorrhaphy with herniotomy by a single surgeon between January and August 2007 was performed evaluating perioperative and postoperative outcomes. A complete intracorporeal laparoscopic technique was utilized to inspect bilateral inguinal canals followed by circumferential division of the peritoneum at the deep ring (patent processus vaginalis) followed by purse string closure of the proximal peritoneum. 31 inguinal hernias were repaired laparoscopically in 26 patients (23 boys, 3 girls). Median age was 36 months (range 1–168 months). 22 children had unilateral inguinal hernia repairs including 2 recurrent hernias; 4 children underwent repair of bilateral inguinal hernias. Mean operating time for unilateral and bilateral inguinal hernia repairs were 48.5±14 min and 61±13.8 min, respectively. 2 patients with a preoperative unilateral inguinal hernia were found to have bilateral inguinal hernias upon laparoscopic examination which were repaired. Postoperative pain was minimal in 20 (77%) patients at discharge. Mean telephone follow-up at 8±9.6 months demonstrated no recurrences to date. Laparoscopic inguinal hernia repair with transperitoneal division of the hernia sac and purse string closure of the proximal peritoneum allows for a minimally invasive option for pediatric inguinal hernia repair that mimics open inguinal hernia repair. At medium term follow-up there have been no recurrences to date, high parent satisfaction, minimal scarring and good cosmetic results.