The latest medical research on Gastroenterology

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Efficacy of enteral glutamine supplementation in patients with severe and predicted severe acute pancreatitis- A randomized controlled trial.

Indian Journal of Gastroenterology

NCT01503320.

Patients with AP admitted within 72 h of onset of symptoms were included. The primary outcome measure was development of infected pancreatic and peri-pancreatic necrosis and in-hospital mortality. High-sensitivity C-reactive protein (HS-CRP) and interleukin-6 (IL-6) were evaluated as markers of inflammation; plasma thiobarbituric acid reactive substances (TBARS) and activities of serum superoxide dismutase and glutathione peroxidase were determined to evaluate oxidative stress; serum polyethylene glycol (PEG) was tested for intestinal permeability; subjective global assessment (SGA) was used for nutritional assessment, and an improvement in organ function was measured by the Modified Marshall score. Intention-to-treat analysis was used. A p-value of < 0.05 was considered statistically significant.

After power calculation, we enrolled 18 patients in the glutamine and 22 in the control arm. There was no significant improvement in the development of infected necrosis and in-hospital mortality between the groups. Improvement in Modified Marshall score was observed in a higher proportion of patients receiving glutamine (15 [83.3%] vs. 12 [54.5%]; p = 0.05). Plasma glutamine levels improved more in glutamine-treated group (432.72 ± 307.83 vs. 618.06 ± 543.29 μM/L; p = 0.004), while it was lower in controls (576.90 ± 477.97 vs. 528.20 ± 410.45 μM/L; p = 0.003). PEG level was lower after glutamine supplementation (39.91 ± 11.97 vs. 32.30 ± 7.39 ng/mL; p = 0.02). Statistically significant reduction in IL-6 concentration was observed in the glutamine group at the end of treatment (87.44 ± 7.1 vs. 63.42 ± 33.7 μM/L; p = 0.02).

Despite absence of improvement in infected necrosis and in-hospital mortality, enteral glutamine supplementation showed improvement in gut permeability, oxidative stress, and a trend towards improvement in organ function as depicted by improvement in the Modified Marshall score.

Reply.

Hepatology

We sincerely thank Dr. Vikas Taneja for his interest in our paper and are more than happy to welcome different perspectives and interpretations on ...

Intermittent restraint-induced sympathetic activation attenuates hepatic steatosis and inflammation in a high fat-diet fed-mouse model.

Am J Physiol

NAFLD is very prevalent worldwide, and is associated with insulin resistance and metabolic syndrome. Stress is physiological and biological respons...

Hepatitis B virus-triggered PTEN/β-catenin/c-Myc signaling enhances PD-L1 expression to promote immune evasion.

Am J Physiol

Hepatitis B virus (HBV) exploits multiple strategies to evade host immune surveillance. Programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling plays a critical role in regulating T cell homeostasis. However, it remains largely unknown as to how HBV infection elevates PD-L1 expression in hepatocytes.

A mouse model of HBV infection was established by hydrodynamic injection with a vector containing 1.3-fold over-length HBV genome (pHBV1.3) via the tail vein. Co-culture experiments with HBV-expressing hepatoma cells and Jurkat T cells were established in vitro.

We observed significant decrease in the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and increase in β-catenin/PD-L1 expression in liver tissues from chronic hepatitis B patients and mice subjected to pHBV1.3 hydrodynamic injection. Mechanistically, decrease in PTEN enhanced β-catenin/c-Myc signaling and PD-L1 expression in HBV-expressing hepatoma cells, which in turn augmented PD-1 expression, lowered IL-2 secretion, and induced T cell apoptosis. However, β-catenin disruption inhibited PTEN-mediated PD-L1 expression, which was accompanied by decreased PD-1 expression, and increased IL-2 production in T cells. Luciferase reporter assays revealed that c-Myc stimulated transcriptional activity of PD-L1. In addition, HBV X protein (HBx) and HBV polymerase (HBp) contributed to PTEN downregulation and β-catenin/PD-L1 upregulation. Strikingly, PTEN overexpression in hepatocytes inhibited β-catenin/PD-L1 signaling and promoted HBV clearance in vivo.

Our findings suggest that HBV-triggered PTEN/β-catenin/c-Myc signaling via HBx and HBp enhances PD-L1 expression, leading to inhibition of T cell response, and promotes HBV immune evasion.

Cure with Interferon Free DAA is Associated with Increased Survival in Patients with HCV related HCC from both East and West.

Hepatology

Survival data among patients with HCV-related HCC after achieving sustained virologic response (SVR) with interferon (IFN)-free direct acting antiv...

Overriding adaptive resistance to sorafenib via combination therapy with SHP2 blockade in hepatocellular carcinoma.

Hepatology

The survival benefit of sorafenib for hepatocellular carcinoma (HCC) patients is unsatisfactory due to the development of adaptive resistance. Incr...

qFIBS: A Novel Automated Technique for Quantitative Evaluation of Fibrosis, Inflammation, Ballooning, and Steatosis in Patients With Nonalcoholic Steatohepatitis.

Hepatology

Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. Clinical trials use the NASH Clinical Research Network (CRN) system...

Post-Liver Transplantation Sinusoidal Obstruction Syndrome With Refractory Ascites Induced by Mycophenolate Mofetil.

Hepatology

Sinusoidal obstruction syndrome (SOS) is a complex entity whose pathogenesis is still not completely defined. Numerous drugs have been associated w...

Botox Injection into the Lower Esophageal Sphincter Induces Hiatal Paralysis and Gastroesophageal Reflux.

Am J Physiol

Endoscopic intrasphincteric injection of botox (ISIB) is used routinely for the treatment of achalasia esophagus and other spastic motor disorders. Studies show that botox reduces the smooth muscle lower esophageal sphincter (LES) pressure. The esophageal hiatus, formed by the right crus of diaphragm surrounds the cranial half of the LES, it works like an external LES.

We studied the effects of ISIB on the LES and hiatal contraction and reflux (GER).

14 patients treated with ISIB were studied. Esophageal manometry-impedance recordings were performed before and after the ISIB. Hiatal contraction was assessed during tidal inspiration, forced inspiration, Muller maneuver and straight leg raise. In 6 subjects, the manometry were repeated 6-12 months after the ISIB. The esophagogastric junction (EGJ) pressure was measured at end-expiration (LES pressure) and at the peak of maneuvers (hiatal contraction). Trans-diaphragmatic pressure (pdi, force of diaphragmatic contraction) was measured at the peak of forced inspiration. GER was measured from impedance recordings.

The EGJ pressure at end-expiration (LES pressure) decreased significantly after botox injection. The peak EGJ pressure at tidal inspiration, forced inspiration, Muller maneuver and straight leg raise was also dramatically reduced by the ISIB. There was no effect of botox on the pdi during forced inspiration. Seven of the 10 subjects demonstrated GER during maneuvers following the ISIB. Six to 12 months after ISIB, hiatal contraction returned to the pre ISIB levels.

ISIB, in addition to decreasing LES pressure, paralyzes the esophageal hiatus (crural diaphragm) and induces GER.

Use of organoids to study regenerative responses to intestinal damage.

Am J Physiol

Intestinal organoid cultures provide an in vitro model system for studying pathways and mechanisms involved in epithelial damage and repair. Derive...

Letter to the Editor: Reply (HEP-19-1537 and 19-1551).

Hepatology

We agree that antiviral treatment affects outcomes in chronic hepatitis B (CHB) patients. In our study, antiviral therapy use was only significant ...

Biallelic mutations in TTC26 (IFT56) cause severe biliary ciliopathy in humans.

Hepatology

The clinical consequences of defective primary cilium (ciliopathies) are characterized by marked phenotypic and genetic heterogeneity. Although fib...