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This article explores the impact of endoscopic gastric plication (EGP) on the portosystemic pressure gradient (PPG) in individuals with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease (cACLD). NAFLD is a prevalent cause of chronic liver disease, and weight loss is the primary treatment. However, lifestyle changes often do not lead to sufficient weight loss. EGP, a procedure that reduces gastric volume, has shown promise in promoting weight loss, but its effect on NAFLD/NASH is not well-studied. This study aims to evaluate the effect of EGP on PPG and weight loss in individuals with NAFLD/NASH and cACLD. The study found that EGP was associated with a significant decrease in PPG, with nearly 80% of patients experiencing a reduction of at least 20%. Furthermore, three-quarters of patients with baseline portal hypertension saw resolution after the procedure. This study suggests that EGP may be an effective treatment option for reducing portal hypertension in individuals with NAFLD and cACLD. [Extracted from the article]

INTRODUCTION: Fibrosis stage is the strongest predictor of mortality in patients with nonalcoholic fatty liver disease (NAFLD). There is currently no approved therapy that specifically targets fibrosis. This study aims to assess the effect of endoscopic gastric plication on hepatic fibrosis in patients with underlying NAFLD. METHODS: This is a retrospective analysis of prospectively collected registry of patients with obesity and NAFLD with clinically significant hepatic fibrosis (‡F2) who underwent endoscopic gastric plication. Fullthickness plications were placed in the gastric body using a commercially available platform to reduce the gastric volume. The primary outcome included various noninvasive tests (NITs) of hepatic fibrosis based on clinical chemistry and/or imaging. The secondary outcomes included NITs of hepatic steatosis, other metabolic outcomes, including hemoglobin A1c, insulin resistance, and total weight loss (TWL), and adverse events.RESULTS: Forty-five patients (age 51 6 13 years and body mass index 40.7 6 6.9 kg/m2) were included. All patients underwent endoscopic gastric plication successfully. At 6–12 months, there were significant reductions in biochemistries (alanine aminotransferase: 49.7 6 36.8 U/L to 24.2 6 12.0 U/L [P < 0.0001], aspartate aminotransferase: 39.1 6 24.1 U/L to 24.1 6 10.0 U/L [P < 0.0001]), composite fibrosis score (NAFLD fibrosis score: 0.48 6 1.51 to 21.18 6 1.56 [P < 0.0001], fibrosis-4 index: 1.4 6 1.2 to 1.2 6 0.7 [P 5 0.03]), and imaging-based markers of fibrosis (vibration-controlled transient elastography: 13.9 6 7.5 kPa to 8.9 6 4.8 kPa (P < 0.0001) and Agile 31: 0.53 6 0.28 to 0.37 6 0.28 [P 5 0.001]). There were significant reductions in controlled attenuation parameter, Homeostatic Model Assessment for Insulin Resistance, and hemoglobin A1c (P < 0.05 for all). At 12 months, patients experienced 15.5% 6 7.9% TWL, with 63% reaching at least 10% TWL. DISCUSSION: Endoscopic gastric plication seems effective at treating NAFLD, with significant reduction in NITs of hepatic fibrosis even in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Results reveal that a kinetic model of protein-mediated ligand transport describes the ligand-protein interactions involved in the intracellular diffusion of ligands, such as fatty acids and amphipathic compounds, which is driven by cytosolic proteins.

A 23-year-old man with liver failure was admitted to a hospital to be evaluated for a liver transplant. He had been diagnosed with chronic liver disease 3 years earlier. He was confused and uncommunicative and an ultrasound scan revealed cirrhosis of the liver. He died on the 6th day of hospitalization. A liver biopsy revealed that the copper content of his liver was substantially higher than normal, leading to the diagnosis of Wilson's disease. This disease is characterized by abnormal accumulation of copper, especially in the liver and brain.

The effect of submicellar bile salt concentrations on model and native membrane permeability to small uncharged molecules such as water, urea and ammonia, was investigated. Findings indicated that at submicellar concentrations, bile salts do not form nonselective convective channels that facilitate transmembrane transport of small uncharged molecules. Therefore, bile salt-mediated transport of specific substrates, rather than nonselective enhancement of membrane permeability, underlies bile salt cytotoxicity for enterocytes and hepatocytes.

A study was conducted on the mechanism of intracellular bilirubin transport. The transfer of uncojugated bilirubin between unilamellar phosphatidylcholine vesicles was observed. Results showed the independence of the bilirubin transfer rate from the acceptor vesicle concentration and also revealed that the rate decreased as the buffer ionic strength increased. These result suggest that the intracellular transport was based on aqeuous diffusion. The results finally indicated the relationship between bilirubin and the presence of phospholipid bilayers at the membrane-water surface.

Despite scant evidence, current guidelines indicate that esophageal varices are a relative contraindication to transesophageal echocardiography (TEE). The aim of this study is to compare the risk of gastrointestinal bleeding following TEE among cirrhotic patients with and without endoscopically‐documented esophageal varices. This is a retrospective analysis of patients with cirrhosis who underwent upper endoscopy within 4 years of TEE at five institutions between January 2000 and March 2020. Primary outcome was overt gastrointestinal bleeding. Secondary outcomes were hemoglobin decline by at least 2 g/dL or blood transfusion within 48 hours following TEE. Of the 191 patients, 79 (41.4%) had esophageal varices (30.4% large). No patient experienced a primary outcome. Secondary outcomes occurred in 52 (27.2%): 28 (35.4%) with esophageal varices and 24 (21.4%) without varices. After propensity‐score covariate adjustment, the odds ratio for a secondary outcome in patients with esophageal varices was 1.49 (95% confidence interval 0.74‐2.99). Restricting analysis to those who underwent endoscopy within 1 year of TEE did not significantly alter results. The risk of a secondary outcome was identical between patients who had upper endoscopy prior (27.5%) versus subsequent (26.7%; P = 1.00) to TEE. Conclusions: Among patients with cirrhosis, there was no overt gastrointestinal bleeding after TEE. The likelihood of a 2 g/dL decline in hemoglobin or blood transfusion within 48 hours following TEE was not significantly higher in patients with esophageal varices after controlling for confounders. Patients who underwent upper endoscopy before TEE did not manifest a lower risk of secondary outcomes versus those who had endoscopy after TEE, suggesting that routine preprocedural endoscopy is of marginal utility. [ABSTRACT FROM AUTHOR]

Goessling, Wolfram, and Stephen D. Zucker. Role of apolipoprotein D in the transport of bilirubin in plasma. Am J Physiol Gastrointest Liver Physiol 279: G356-G365, 2000.-- Apolipoprotein D (apo D) is a 30-kDa glycoprotein of unknown function that is associated with high-density lipoproteins (HDL). Because unconjugated bilirubin has been shown to bind apo D with a 0.8:1 stoichiometry, we examined the contribution of this protein to transport of bilirubin in human plasma. Density gradient centrifugation analysis using physiological concentrations of [[sup.14]C]bilirubin reveals that 9% of unconjugated bilirubin is associated with HDL, with the remaining pigment bound primarily to serum proteins (i.e., albumin). The percentage of total plasma bilirubin bound to HDL was found to increase proportionally with bilirubin concentration. Affinity of human apo D for bilirubin was determined by steady-state fluorescence quenching, with Scatchard analysis demonstrating a single binding site for unconjugated bilirubin with an affinity constant ([K.sub.a]) of ~3 x [10.sup.7] [M.sup.-1]. Incorporation of apo D into phosphatidylcholine vesicles had no effect on [K.sub.a], suggesting that a lipid environment does not alter the affinity of the protein for bilirubin. Using stopped-flow techniques, the first-order rate constant for bilirubin dissociation from apo D was measured at 5.4 [s.sup.-1] (half-time = 129 ms). Our findings indicate that HDL is the principal nonalbumin carrier of bilirubin in human plasma and further support the proposition that the affinity of HDL for bilirubin is primarily the result of binding to apo D. high-density lipoproteins; human serum albumin; dissociation rate; cholesterol; cholic acid