Risk Factors and Cardiovascular Events in Orthotopic Liver Transplantation.

Background And Aims: Patients undergoing liver transplantation often have significant cardiovascular risk factors and may experience cardiac-related morbidity and mortality. The aim of this study was to assess the frequency of cardiovascular risk factors and outcomes in this population, and to identify factors predictive of post-transplant cardiac morbidity and mortality.

Methods: We studied 261 patients who underwent liver transplantation at a single Veterans' Affairs Medical center between 1997 and 2015 to evaluate new cardiovascular events post-transplantation.

Coffee modulates insulin-hepatocyte nuclear factor-4α-Cyp7b1 pathway and reduces oxysterol-driven liver toxicity in a nonalcoholic fatty liver disease mouse model.

Oxysterol 7α-hydroxylase (CYP7B1) controls the levels of intracellular regulatory oxysterols generated by the "acidic pathway" of cholesterol metabolism. Previously, we demonstrated that an inability to upregulate CYP7B1 in the setting of insulin resistance leads to the accumulation of cholesterol metabolites such as ()26-hydroxycholesterol (26HC) that initiate and promote hepatocyte injury; followed by an inflammatory response. The current study demonstrates that dietary coffee improves insulin resistance and restores Cyp7b1 levels in a well-characterized Western diet (WD)-induced nonalcoholic fatty liver disease (NAFLD) mouse model.

Liver-Unrelated Comorbid Conditions Do Not Affect Cognitive Performance or Hepatic Encephalopathy Progression in Cirrhosis.

Introduction: We aimed to determine the effect of comorbidities on covert hepatic encephalopathy (CHE) diagnosis and overt hepatic encephalopathy (OHE) development.

Methods: Cirrhotic outpatients underwent CHE testing and 2-year follow-up. Cox regression was performed for time to OHE.

Sex is associated with differences in gut microbial composition and function in hepatic encephalopathy.

Background & Aims: Altered microbiota can affect the gut-liver-brain axis in cirrhosis and hepatic encephalopathy (HE), but the impact of sex on these changes is unclear. We aimed to determine differences in fecal microbiota composition/functionality between men and women with cirrhosis and HE on differing treatments.

Methods: Cross-sectional stool microbiome composition (16s rRNA sequencing) and microbial functional analyses were performed in men and women with cirrhosis, and controls.

High Glucose Induces Lipid Accumulation via 25-Hydroxycholesterol DNA-CpG Methylation.

This work investigates the relationship between high-glucose (HG) culture, CpG methylation of genes involved in cell signaling pathways, and the regulation of carbohydrate and lipid metabolism in hepatocytes. The results indicate that HG leads to an increase in nuclear 25-hydroxycholesterol (25HC), which specifically activates DNA methyltransferase-1 (DNMT1), and regulates gene expression involved in intracellular lipid metabolism. The results show significant increases in CpG levels in at least 2,225 genes involved in 57 signaling pathways.

Liver Transplant Is Associated with Sustained Improvement in Tandem Gait and Risk of Falls.

Background: Cirrhosis is associated with poor health-related quality of life (HRQOL), cognitive dysfunction (CD), and lack of coordination leading to falls. Tandem gait (TG; heel-toe) can be used to assess coordination. The impact and relationship between CD, TG and falls pre-/post-liver transplant (LT) is unclear.

Addition of [ F]Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography to Cross-Sectional Imaging Improves Staging and Alters Management in Hepatocellular Carcinoma.

In this work, we characterize the value of positron emission tomography (PET) with computed tomography (CT) in combination with cross-sectional imaging for staging and prognostication of hepatocellular carcinoma (HCC) patients. In this retrospective cohort study, HCC patients underwent PET-CT after initial staging with contrast-enhanced CT or magnetic resonance imaging (MRI). The benefit of PET-CT was measured by the identification of new HCC lesions, and potential harm was quantified by the number of false positives and subsequent diagnostic evaluation.

Use of Telehealth Expedites Evaluation and Listing of Patients Referred for Liver Transplantation.

Background & Aims: Liver transplantation is the only treatment that increases survival times of patients with decompensated cirrhosis. Patients who live farther away from a transplant center are disadvantaged. Health care delivery via telehealth is an effective way to manage patients with decompensated cirrhosis remotely.

Serum and urinary metabolomics and outcomes in cirrhosis.

Background: Cirrhosis can alter several metabolic pathways. Metabolomics could prognosticate outcomes like hepatic encephalopathy (HE), transplant, hospitalization and death.

Aim: Determine changes in serum and urine metabolomics in cirrhotics who develop outcomes.

Posttraumatic stress disorder is associated with altered gut microbiota that modulates cognitive performance in veterans with cirrhosis.

Posttraumatic stress disorder (PTSD) is associated with cirrhosis in veterans, and therapeutic results are suboptimal. An altered gut-liver-brain axis exists in cirrhosis due to hepatic encephalopathy (HE), but the added impact of PTSD is unclear. The aim of this study was to define linkages between gut microbiota and cognition in cirrhosis with/without PTSD.

Specific Gut and Salivary Microbiota Patterns Are Linked With Different Cognitive Testing Strategies in Minimal Hepatic Encephalopathy.

Objectives: Minimal hepatic encephalopathy (MHE) is epidemic in cirrhosis, but testing strategies often have poor concordance. Altered gut/salivary microbiota occur in cirrhosis and could be related to MHE. Our aim was to determine microbial signatures of individual cognitive tests and define the role of microbiota in the diagnosis of MHE.

Diagnosis of covert hepatic encephalopathy: a multi-center study testing the utility of single versus combined testing.

Covert hepatic encephalopathy (CHE) affects cognition in a multidimensional fashion. Current guidelines recommend performing Psychometric Hepatic Encephalopathy Score (PHES) and a second test to diagnose CHE for multi-center trials. We aimed to determine if a two-test combination strategy improved CHE diagnosis agreement, and accuracy to predict overt hepatic encephalopathy (OHE), compared to single testing.

Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis.

Objectives: Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis.

Methods: Four cohorts were enrolled.

Telehealth-Based Evaluation Identifies Patients Who Are Not Candidates for Liver Transplantation.

The burden of chronic liver disease has increased exponentially, driving more patients toward orthotopic liver transplant (OLT) evaluation. Because of limited access to transplant centers, patients often travel long distances to be evaluated for OLT. Liver transplantation in the VA system is offered at 6 Veterans Affairs transplant centers (VATCs) across the United States, including Richmond.

Gut microbial RNA and DNA analysis predicts hospitalizations in cirrhosis.

Background: Cirrhosis is associated with gut microbial changes, but current 16S rDNA techniques sequence both dead and live bacteria. We aimed to determine the rRNA content compared with DNA from the same stool sample to evaluate cirrhosis progression and predict hospitalizations.

Methods: Cirrhotics and controls provided stool for RNA and DNA analysis.

Alterations in gut microbial function following liver transplant.

Liver transplantation (LT) improves daily function and ameliorates gut microbial composition. However, the effect of LT on microbial functionality, which can be related to overall patient benefit, is unclear and could affect the post-LT course. The aims were to determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism, and lipidomics.

Gut microbial composition can differentially regulate bile acid synthesis in humanized mice.

We previously reported that alcohol drinkers with and without cirrhosis showed a significant increase in fecal bile acid secretion compared to nondrinkers. We hypothesized this may be due to activation by alcohol of hepatic cyclic adenosine monophosphate responsive element-binding protein 3-like protein 3 (CREBH), which induces cholesterol 7α-hydroxylase (Cyp7a1). Alternatively, the gut microbiota composition in the absence of alcohol might increase bile acid synthesis by up-regulating Cyp7a1.

Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort.

Unlabelled: The relative ranking of cirrhosis-related deaths differs between high-/middle-income countries. Gut microbiome is affected in cirrhosis and is related to diet. Our aim was to determine the effect of differing dietary habits on gut microbiota and clinical outcomes.

Effect of Post-Traumatic Stress Disorder on Cognitive Function and Covert Hepatic Encephalopathy Diagnosis in Cirrhotic Veterans.

Background: In veterans, post-traumatic stress disorder (PTSD) is often associated with substance abuse, which in turn can lead to cirrhosis. Cirrhotic patients are prone to cognitive impairment, which is typically due to covert hepatic encephalopathy (CHE), but can also be affected by PTSD. The aim was to define the impact of PTSD on cognitive performance and the diagnosis of CHE in cirrhotic patients.

Brain Integrity Changes Underlying Cognitive and Functional Recovery Postliver Transplant Continue to Evolve Over 1 Year.

Background: There is evidence of brain recovery on brain magnetic resonance imaging (MRI) early postliver transplant (LT), but the longer-term impact is unclear. The aim of this study was to determine the change in brain MRI parameters, cognition, and health-related quality of life (HRQOL) between 6 and 12 months post-LT.

Methods: Listed cirrhotics underwent cognitive, HRQOL and brain MRI pre-LT, 6 months (post-LT1), and 1-year (post-LT2) post-LT.

Continued Alcohol Misuse in Human Cirrhosis is Associated with an Impaired Gut-Liver Axis.

Background: Cirrhosis and alcohol can independently affect the gut-liver axis with systemic inflammation. However, their concurrent impact in humans is unclear.

Methods: Our aim was to determine the effect of continued alcohol misuse on the gut-liver axis in cirrhotic patients.

Overt hepatic encephalopathy impairs learning on the EncephalApp stroop which is reversible after liver transplantation.

After an initial exposure, patients can develop test-taking/learning strategies called the "test sophistication effect." Patients with cirrhosis with prior overt hepatic encephalopathy (OHE) could have persistent learning impairments. The aim was to define learning/test sophistication on EncephalApp (downloadable application) in OHE patients compared with patients without prior overt hepatic encephalopathy (no-OHE) patients and controls cross-sectionally and longitudinally.