Peripheral arterial disease in hemodialysis patients 10 years later.

Background And Objective: Patients with chronic kidney disease (CKD) on hemodialysis present high cardiovascular comorbidity. Peripheral arterial disease (PAD) is associated with higher mortality and the interest in its early detection and treatment is increasing. The objective of this study is to determine the frequency and severity of symptomatic PAD, and to establish its relationship with mortality in HD patients that have received treated early and compare them with a cohort of our center already reported.

Metabolic liver cancer: associations of rare and common germline variants in one-carbon metabolism and DNA methylation genes.

Animal studies implicate one-carbon metabolism and DNA methylation genes in hepatocellular carcinoma (HCC) development in the setting of metabolic perturbations. Using human samples, we investigated the associations between common and rare variants in these closely related biochemical pathways and risk for metabolic HCC development in a multicenter international study. We performed targeted exome sequencing of 64 genes among 556 metabolic HCC cases and 643 cancer-free controls with metabolic conditions.

Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD.

Background And Aims: Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition from simple steatosis to steatohepatitis.

Methods: EpCAM and CD133 liver proteins and EpCAM+ CD133+ EVs levels were analysed in 31 C57BL/6J mice fed with a chow or high fat, high cholesterol and carbohydrates diet (HFHCC) for 52 weeks.

Extracellular Vesicles as Biomarkers in Liver Disease.

Extracellular vesicles (EVs) are membrane-derived vesicles released by a variety of cell types, including hepatocytes, hepatic stellate cells, and immune cells in normal and pathological conditions. Depending on their biogenesis, there is a complex repertoire of EVs that differ in size and origin. EVs can carry lipids, proteins, coding and non-coding RNAs, and mitochondrial DNA causing alterations to the recipient cells, functioning as intercellular mediators of cell-cell communication (auto-, para-, juxta-, or even endocrine).

Emerging pharmacological treatment options for MAFLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) prevalence and incidence is rising globally. It is associated with metabolic comorbidities, obesity, overweight, type 2 diabetes mellitus, and at least two metabolic risk factors, such as hypertension, hypertriglyceridemia, hypercholesterolemia, insulin resistance, and cardiovascular risk, increasing the risk of mortality. The excessive accumulation of fat comprises apoptosis, necrosis, inflammation and ballooning degeneration progressing to fibrosis, cirrhosis, and liver decompensations including hepatocellular carcinoma development.

Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception.

Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Peripheral blood samples were extracted from LC and HCC patients at different disease stages.

Impact of a Loss-of-Function Variant in on Hepatic Decompensation and Mortality in Cirrhotic Patients.

A common splice variant in HSD17B13 (rs72613567:TA) was recently found to be associated with a reduced risk of developing chronic liver disease in NAFLD patients and a reduced risk of progression to advanced fibrosis and cirrhosis. In this study, we aimed to evaluate the prognosis of cirrhotic patients harboring this variant. We performed a retrospective analysis on 483 prospectively recruited patients from four different hospitals in Spain, followed-up for at least 5 years.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

Background & Aims: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population.

Methods: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020.

Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, reflecting the current epidemics of obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. NAFLD is characterized by the accumulation of fat in the liver, and is known to be a cause of cirrhosis. Although many pathways have been proposed, the cause of NAFLD-linked fibrosis progression is still unclear, which posed challenges for the development of new therapies to prevent NASH-related cirrhosis and hepatocellular carcinoma.

Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD.

Background: NAFLD clinical trials have shown suboptimal results, particularly for liver fibrosis, despite the robust preclinical drug development. We aimed to assess the histological response after the experimental treatment versus placebo by carrying out a meta-analysis of NAFLD clinical trials.

Methods: After a systematic review of NAFLD clinical trials to May 2021, applying strict selection criteria, the following primary outcomes were observed: (a) NASH resolution, with no worsening of fibrosis when available; (b) fibrosis improvement  ≥ 1 stage, with no worsening of NAS when available; (c) worsening of NAS; (d) worsening of liver fibrosis  ≥ 1 stage, including the progression to cirrhosis on histopathology.

Long non-coding RNA H19 as a biomarker for hepatocellular carcinoma.

Background And Aims: Liver cancer stem cells (CSCs) could be involved in the carcinogenesis, recurrence, metastasis and chemoresistance of hepatocellular carcinoma (HCC). The aim of this study was to explore the role of lncRNA-H19 as a biomarker for liver cancer.

Methods: LncRNA-H19 expression levels and the functional assays were conducted in EpCAM CD133 CSCs and C57BL/6J mice fed with a high-fat high-cholesterol carbohydrate (HFHCC) or standard diet for 52 weeks.

Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation.

The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a functional variant located in carbamoyl phosphate synthetase-1 (CPS1) gene.

Combination of squamous cell carcinoma antigen immunocomplex and alpha-fetoprotein in mid- and long-term prediction of hepatocellular carcinoma among cirrhotic patients.

Background: The combination of alpha-fetoprotein (AFP) and squamous cell carcinoma antigen immunocomplex (SCCA-IgM) have been proposed for its use in the screening of hepatocellular carcinoma (HCC). Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.

Aim: To determine the role of the combination of SCCA-IgM and AFP in predicting mid- and long-term appearance of HCC.

A Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapy.

Background: Metabolic-associated fatty liver disease (MAFLD) has risen as one of the leading etiologies for hepatocellular carcinoma (HCC). Oncogenes have been suggested to be responsible for the high risk of MAFLD-related HCC. We analyzed the impact of the proto-oncogene c-MYC in the development of human and murine MAFLD and MAFLD-associated HCC.

Serum chemerin in a cohort of Colombian patients with primary osteoarthritis.

Background And Purpose: Osteoarthritis (OA) is considered the most common degenerative joint pathology in the adult population, being an important cause of disability worldwide, and its prevalence is increasingly associated with different factors, including obesity. Obesity together with metabolic syndrome have been associated with a pro-inflammatory state due to the release of cytokines that induce changes in cartilage metabolism. Chemerin is an adipokine secreted mainly by adipocytes and its final action is to increase the production of IL-6, IL-8, IL-1b, TNF-a and metalloproteinases by macrophages, dendritic cells and chondrocytes, which are responsible for damage to the articular cartilage.

A new algorithm shows superior ability to discriminate liver fibrosis stages in chronic hepatitis C.

Previous evidence suggests that sialic acid-binding Ig-like lectin 7 (Siglec-7) protein is significantly increased in patients with chronic hepatitis C virus (HCV) infection and directly correlates with clinical parameters of liver inflammation and fibrosis. The aim of this study was to determine the diagnostic value of Siglec-7 as a non-invasive tool to assess liver fibrosis in patients with chronic hepatitis C in a cross-sectional study. Serum levels of Siglec-7 were retrospectively tested in 1007 consecutive patients with chronic HCV infection recruited at three different European sites and data examined by the 'imperfect gold-standard' statistical analysis.

Development and Validation of a Clinical-Genetic Risk Score to Predict Hepatic Encephalopathy in Patients With Liver Cirrhosis.

Introduction: We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical-genetic risk score.

Methods: Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant, or death. Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS.

The Search of a Malaria Vaccine: The Time for Modified Immuno-Potentiating Probes.

Malaria is a deadly disease that takes the lives of more than 420,000 people a year and is responsible for more than 229 million clinical cases globally. In 2019, 95% of malaria morbidity occurred in African countries. The development of a highly protective vaccine is an urgent task that remains to be solved.

Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study.

Introduction: Hepatitis C virus (HCV) infection has been related to increased cardiovascular (CV) risk. The aim of this study was to analyze the impact of sustained virological response (SVR) on endothelial dysfunction and subclinical atherosclerosis in patients with hepatitis C virus treated with direct-acting antiviral agents.

Methods: A total of 114 patients were prospectively recruited and underwent CV risk assessment including (i) endothelial dysfunction determined through laser Doppler flowmetry and (ii) subclinical atherosclerosis, elucidated by the ankle-brachial index (ABI).

Serum chemerin in a cohort of Colombian patients with primary osteoarthritis.

Background And Purpose: Osteoarthritis (OA) is considered the most common degenerative joint pathology in the adult population, being an important cause of disability worldwide, and its prevalence is increasingly associated with different factors, including obesity. Obesity together with metabolic syndrome have been associated with a pro-inflammatory state due to the release of cytokines that induce changes in cartilage metabolism. Chemerin is an adipokine secreted mainly by adipocytes and its final action is to increase the production of IL-6, IL-8, IL-1b, TNF-α and metalloproteinases by macrophages, dendritic cells and chondrocytes, which are responsible for damage to the articular cartilage.

COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction.

International and multicenter real-world study of sorafenib-treated patients with hepatocellular carcinoma under dialysis.

Background & Aims: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population.

Methods: We report a multicenter study comprising patients from Latin America and Europe.

Water-soluble extracts from edible mushrooms (Agaricus bisporus) as inhibitors of hepatitis C viral replication.

Hepatitis C virus (HCV) is the main agent responsible for chronic liver disease. Recent advances in anti-HCV treatment strategies have significantly increased the viral clearance rate (>90%). However, sustained antiviral responses vary in different cohorts, and high costs limit the broad use of direct-acting antivirals (DAAs).