Advances in the management of alcohol-associated liver disease.

Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g.

Increasing practice and acceptable outcomes of high-MELD living donor liver transplantation in the USA.

Recent deceased-donor allocation changes in the United States may have increased high-Model for End-Stage Liver Disease (MELD) living donor liver transplantation (LDLT); however, outcomes in these patients remain poorly defined. We aimed to examine the impact of the MELD score on LDLT outcomes. Using UNOS data (January 1, 2010-December 31, 2021), LDLT recipients were identified and stratified into low-MELD (<15), intermediate-MELD (15-24), and high-MELD (≥25) groups.

High Neutrophil-Lymphocyte Ratio and Delta Neutrophil-Lymphocyte Ratio Are Associated with Increased Mortality in Patients with Hepatocellular Cancer.

Background: The neutrophil-lymphocyte ratio (NLR) has been proposed as a prognostic biomarker for cirrhosis and non-liver malignancies. We aimed to evaluate the prognostic value of NLR in a diverse cohort of patients with hepatocellular carcinoma (HCC).

Methods: We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at two large US health systems.

More Than a Rash: Recurrent Hepatocellular Carcinoma After Liver Transplantation.

Recurrent hepatocellular carcinoma (HCC) after liver transplant is uncommon in patients who have favorable pretransplant characteristics. We present a 56-year-old man with a history of liver transplant 8 weeks prior for hepatitis C cirrhosis and HCC who presented for shortness of breath. He was found to have a microangiopathic hemolytic anemia and an erythematous, nodular skin rash on his left lower abdomen.

Liver volume in the cirrhotic patient: does size matter?

Background: While it is established that cirrhosis results in a decrease in liver volume (LV), whether LV itself predicts patient survival is unknown. We hypothesize that estimated LV is an important prognostic indicator in patients with cirrhosis.

Methods: Data was gathered retrospectively from consecutive patients evaluated for a liver transplant from January 2001 to June 2006.

Cysteine sulfinic acid decarboxylase regulation: A role for farnesoid X receptor and small heterodimer partner in murine hepatic taurine metabolism.

Aim: Bile acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor 15/19 (FGF15/19). We hypothesized that hepatic cysteine sulfinic acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile acids (BA). The aim of this study was to investigate CSAD regulation by BA dependent regulatory mechanisms.

Intestine-Specific Mttp Deletion Increases the Severity of Experimental Colitis and Leads to Greater Tumor Burden in a Model of Colitis Associated Cancer.

Background: Gut derived lipid factors have been implicated in systemic injury and inflammation but the precise pathways involved are unknown. In addition, dietary fat intake and obesity are independent risk factors for the development of colorectal cancer. Here we studied the severity of experimental colitis and the development of colitis associated cancer (CAC) in mice with an inducible block in chylomicron secretion and fat malabsorption, following intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO).

IDO1 metabolites activate β-catenin signaling to promote cancer cell proliferation and colon tumorigenesis in mice.

Background & Aims: Indoleamine 2,3 dioxygenase-1 (IDO1) catabolizes tryptophan along the kynurenine pathway. Although IDO1 is expressed in inflamed and neoplastic epithelial cells of the colon, its role in colon tumorigenesis is not well understood. We used genetic and pharmacologic approaches to manipulate IDO1 activity in mice with colitis-associated cancer and human colon cancer cell lines.

Cholesterol and nonalcoholic fatty liver disease: renewed focus on an old villain.

Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular and liver-related mortality. NAFLD is characterized by both triglyceride and free cholesterol (FC) accumulation without a corresponding increment in cholesterol esters. The aim of this study was to evaluate the expression of cholesterol metabolic genes in NAFLD and relate these to disease phenotype.

MicroRNAs and liver disease.

Posttranscriptional regulation of gene expression is now recognized as an important contributor to disease pathogenesis, whose mechanisms include alterations in the function of stability and translational elements within both coding and noncoding regions of messenger RNA. A major component in this regulatory paradigm is the binding both to RNA stability as well as to translational control elements by microRNAs (miRNAs). miRNAs are noncoding endogenously transcribed RNAs that undergo a well-characterized series of processing steps that generate short single-stranded (∼20-22) RNA fragments that bind to complementary regions within a range of targets and in turn lead to mRNA degradation or attenuated translation as a result of trafficking to processing bodies.

Therapeutic RNA manipulation in liver disease.

Posttranscriptional regulation of gene expression is increasingly recognized as a model for inherited and acquired disease. Recent work has expanded understanding of the range of mechanisms that regulate several of these distinct steps, including messenger RNA (mRNA) splicing, trafficking, and/or stability. Each of these pathways is implicated in disease pathogenesis, and each represents important avenues for therapeutic intervention.

Decreased expression of cholesterol 7alpha-hydroxylase and altered bile acid metabolism in Apobec-1-/- mice lead to increased gallstone susceptibility.

Quantitative trait mapping in mice identified a susceptibility locus for gallstones (Lith6) spanning the Apobec-1 locus, the structural gene encoding the RNA-specific cytidine deaminase responsible for production of apolipoprotein B48 in mammalian small intestine and rodent liver. This observation prompted us to compare dietary gallstone susceptibility in Apobec-1(-/-) mice and congenic C57BL/6 wild type controls. When fed a lithogenic diet (LD) for 2 weeks, 90% Apobec-1(-/-) mice developed solid gallstones in comparison with 16% wild type controls.

Pancreatitis following Olanzapine Therapy: A Report of Three Cases.

Context: Atypical antipsychotic agents (clozapine, olanzapine) have been linked to metabolic effects and acute pancreatitis.

Case Report: We reviewed the inpatient and outpatient records of three patients who developed acute pancreatitis while being treated with olanzapine. The mean age of the patients was 37.

Loss of nuclear receptor SHP impairs but does not eliminate negative feedback regulation of bile acid synthesis.

The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid synthesis was examined. Loss of SHP in mice caused abnormal accumulation and increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids induced liver damage and restored feedback regulation.