Reproducibility of EUS-guided shear wave elastography for assessment of hepatic fibrosis: a prospective pilot cohort study.

Background And Aims: Non-invasive assessment of liver fibrosis is important in the management of liver disease. EUS-guided shear wave elastography (EUS-SWE) is a newer technology that can measure liver stiffness, thereby estimating hepatic fibrosis. There is limited data comparing EUS-SWE to vibration controlled transient elastography (VCTE) using liver biopsy as the gold standard, and the reproducibility of EUS-SWE measurements is not known.

NADPH oxidase 1 promotes hepatic steatosis in obese mice and is abrogated by augmented skeletal muscle mass.

Exercise as a lifestyle modification is a frontline therapy for nonalcoholic fatty liver disease (NAFLD), but how components of exercise attenuate steatosis is unclear. To uncouple the effect of increased muscle mass from weight loss in obesity, myostatin knockout mice were bred on a lean and obese background. Myostatin deletion increases gastrocnemius (Gastrocn.

Changing Trends in Liver Biopsy Practices: A Single-Center Analysis.

Introduction To assess the trends for liver biopsy (LB) indications, technique, and histopathologic diagnosis, we retrospectively evaluated liver biopsies in two one-year periods, separated by a decade. Methods A pathology database query was performed for all parenchymal LB in patients over 18 years (11/2017 to 10/2018) and compared to those performed over a one-year period, a decade ago. We identified 427 parenchymal liver biopsies in the recent group and 166 in the decade-old group.

Hemorrhagic Ascites Is Associated With Reduced Survival in Cirrhosis: A Systematic Review and Meta-Analysis.

Background: Hemorrhagic ascites is characterized as red blood cell count greater than 10,000/mm. In cirrhosis, ascites is an event of decompensation, and associated with poor prognosis. However, significance of hemorrhagic ascites is unclear.

"Bioelectrical impedance analysis in managing sarcopenic obesity in NAFLD".

Introduction: Sarcopenic obesity and its association with nonalcoholic fatty liver disease (NAFLD) is under-recognized by many healthcare providers in Western medicine due to the lack of awareness and diagnostic guidelines. The result is delayed recognition and treatment, which leads to further health deterioration and increased healthcare costs. Sarcopenic obesity is characterized by the presence of increased fat mass in combination with muscle catabolism related to chronic inflammation and/or inactivity.

A Comprehensive Review Evaluating the Impact of Protein Source (Vegetarian vs. Meat Based) in Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a common neurological consequence in patients with cirrhosis and has a healthcare burden of USD 5370 to 50,120 per patient annually. HE significantly hampers the quality of life and is a major cause of morbidity and mortality. Patients with cirrhosis are at a high risk for protein-calorie malnutrition due to altered metabolism.

M3 muscarinic receptor activation reduces hepatocyte lipid accumulation via CaMKKβ/AMPK pathway.

Previously, we reported that hepatic muscarinic receptors modulate both acute and chronic liver injury, however, the role of muscarinic receptors in fatty liver disease is unclear. We observed in patients who underwent weight loss surgery, a decrease in hepatic expression of M3 muscarinic receptors (M3R). We also observed that fat loading of hepatocytes, increased M3R expression.

MicroRNA-34a (miR-34a) Mediates Retinal Endothelial Cell Premature Senescence through Mitochondrial Dysfunction and Loss of Antioxidant Activities.

Stress-associated premature senescence (SAPS) is involved in retinal microvascular injury and diabetic retinopathy. We have investigated the role and mode of action of miR-34a in retinal endothelial cells senescence in response to glucidic stress. Human retinal microvascular endothelial cells (HuREC) were exposed to glucidic stress (high glucose (HG) = 25 mM d-glucose) and compared to cells exposed to normal glucose (NG = 5 mM) or the osmotic control l-glucose (LG = 25 mM).

Bi-lobar liver biopsy via EUS enhances the assessment of disease severity in patients with non-alcoholic steatohepatitis.

Background: In patients with non-alcoholic fatty liver disease (NAFLD), all-cause mortality increases with fibrosis stage. Liver biopsy (LB), performed predominantly in the right lobe, assesses fibrosis, however, right lobe LB may not be sufficient due to histological variation in different lobes. Endoscopic ultrasound (EUS) allows for biopsy of right and left liver lobes in the same setting.

Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis.

GPR109A agonists have been used for the treatment of obesity however, the role of GPR109A in regulating aging-associated alterations in lipid metabolism is unknown. In this study we used mice to investigate the effect of aging in the regulation of lipid accumulation. We observed that in mouse and human livers, in addition to Kupffer cells, GPR109A is expressed in hepatocytes.

Deoxycholylglycine, a conjugated secondary bile acid, reduces vascular tone by attenuating Ca sensitivity via rho kinase pathway.

Patients with cirrhosis have reduced systemic vascular resistance and elevated circulating bile acids (BAs). Previously, we showed that secondary conjugated BAs impair vascular tone by reducing vascular smooth muscle cell (VSMC) Ca influx. In this study, we investigated the effect of deoxycholylglycine (DCG), on Ca sensitivity in reducing vascular tone.

Targeting Cholinergic System to Modulate Liver Injury.

Over the past few decades, evidence accumulated to indicate that parasympathetic innervation regulates liver injury and regeneration. Liver derives its parasympathetic input via vagus nerve. In animal models, vagus nerve stimulation and transection are frequently used to determine the impact of parasympathetic input on liver injury responses.

Hepatocellular carcinoma in non-alcoholic steatohepatitis: Current knowledge and implications for management.

With the prevalence of hepatitis C virus expected to decline, the proportion of hepatocellular carcinoma (HCC) related to non-alcoholic steatohepatitis (NASH) is anticipated to increase exponentially due to the growing epidemic of obesity and diabetes. The annual incidence rate of developing HCC in patients with NASH-related cirrhosis is not clearly understood with rates ranging from 2.6%-12.

Characterization of pressure-mediated vascular tone in resistance arteries from bile duct-ligated rats.

In cirrhosis, changes in pressure-mediated vascular tone, a key determinant of systemic vascular resistance (SVR), are unknown. To address this gap in knowledge, we assessed ex vivo dynamics of pressurized mesenteric resistance arteries (diameter ~ 260 μm) from bile duct-ligated (BDL) and sham-operated (SHAM) rats and determined the underlying mechanisms. At isobaric intraluminal pressure (70 mmHg) as well as with step-wise increase in pressure (10-110 mmHg), arteries from SHAM-rats constricted more than BDL-rats, and had reduced luminal area.

Naturally Occurring Nrf2 Activators: Potential in Treatment of Liver Injury.

Oxidative stress plays a major role in acute and chronic liver injury. In hepatocytes, oxidative stress frequently triggers antioxidant response by activating nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, which upregulates various cytoprotective genes. Thus, Nrf2 is considered a potential therapeutic target to halt liver injury.

A comparative study on postoperative pain relief in laparoscopic cholecystectomy: Intraperitoneal bupivacaine versus combination of bupivacaine and buprenorphine.

Context: To assess the analgesic efficacy of the combination of bupivacaine and buprenorphine in alleviating postoperative pain following laparoscopic cholecystectomy.

Aims: Laparoscopic cholecystectomy is comparatively advantageous as it offers less pain in the postoperative period and requires a shorter hospital stay. There are only a few studies performed to evaluate the analgesic efficacy of intraperitoneal instillation of buprenorphine and bupivacaine during laparoscopic cholecystectomy.

Data regarding M1 muscarinic receptor-mediated modulation of hepatic catalase activity in response to oxidative stress.

We recently demonstrated the role of M1 muscarinic receptors (M1R) in modulating oxidative stress in liver and hepatocytes (Urrunaga et al., 2015) [1]. Here we provide data regarding the effect of a novel M1R agonist, VU0357017 (Lebois et al.

M1 Muscarinic Receptor Deficiency Attenuates Azoxymethane-Induced Chronic Liver Injury in Mice.

Cholinergic nervous system regulates liver injury. However, the role of M1 muscarinic receptors (M1R) in modulating chronic liver injury is uncertain. To address this gap in knowledge we treated M1R-deficient and WT mice with azoxymethane (AOM) for six weeks and assessed liver injury responses 14 weeks after the last dose of AOM.

Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice.

Withaferin-A (WA) has anti-oxidant activities however, its therapeutic potential in acetaminophen (APAP) hepatotoxicity is unknown. We performed a proof-of-concept study to assess the therapeutic potential of WA in a mouse model that mimics APAP-induced liver injury (AILI) in humans. Overnight fasted C57BL/6NTac (5-6 wk.

Assessing Myogenic Response and Vasoactivity In Resistance Mesenteric Arteries Using Pressure Myography.

Small resistance arteries constrict and dilate respectively in response to increased or decreased intraluminal pressure; this phenomenon known as myogenic response is a key regulator of local blood flow. In isobaric conditions small resistance arteries develop sustained constriction known as myogenic tone (MT), which is a major determinant of systemic vascular resistance (SVR). Hence, ex vivo pressurized preparations of small resistance arteries are major tools to study microvascular function in near-physiological states.

M1 muscarinic receptors modify oxidative stress response to acetaminophen-induced acute liver injury.

The role of muscarinic receptor subtypes in modulating acute liver injury is unknown. We detected M1 muscarinic receptor (M1R) expression in human and murine hepatocytes, and investigated the consequences of M1R deficiency on acute liver injury in vivo and inhibiting M1R activation on hepatocyte injury in vitro. Age-matched wild-type (WT) and M1R-deficient (Chrm1(-/-)) male mice were injected intraperitoneally with 200mg/kg acetaminophen (APAP) and euthanized 0, 2, 4, 16, 24, and 36h later.