The Rising Global Burden of MASLD and Other Metabolic Diseases (2000-2021).

Background: Metabolic diseases are a public health threat to diverse populations worldwide. This study aims to update the epidemiological trends of metabolic diseases across regions and sociodemographic stratifications using the Global Burden of Diseases Study 2021.

Methods: This study focused on metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) along with obesity, hypertension, and dyslipidemia.

Enhanced Spatial Transcriptomics Analysis of Mouse Lung Tissues Reveals Cell-Specific Gene Expression Changes Associated with Pulmonary Hypertension.

Spatial transcriptomics technologies have emerged as powerful tools for understanding cellular identity and function within the natural spatial context of tissues. Traditional transcriptomics techniques, such as bulk and single-cell RNA sequencing, lose this spatial information, which is critical for addressing many biological questions. Here, we present a protocol for high-resolution spatial transcriptomics using fixed frozen mouse lung sections mounted on 10X Genomics Xenium slides.

Increased Mortality Among Lean Versus Non-Lean Adults With MASLD: A Multicenter Study.

Background And Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide. Since the adoption of the new terminology from the Delphi Consensus statement, there has not been a large multicenter cohort study of MASLD among lean versus non-lean individuals. This study aims to assess prevalence and incidence outcomes among lean and non-lean individuals with MASLD in a diverse patient cohort.

Single-Cell and Spatial Transcriptomics Identified Fatty Acid-Binding Proteins Controlling Endothelial Glycolytic and Arterial Programming in Pulmonary Hypertension.

Background: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for patients with PAH. Recent studies showed that FABP (fatty acid-binding protein) 4 and FABP5 are expressed in endothelial cells (ECs) across multiple tissues, and circulating FABP4 level is elevated in patients with PAH.

Alcohol-Attributable Cancer: Update From the Global Burden of Disease 2021 Study.

Background And Aims: Alcohol is a major risk factor for cancer development. Our study aimed to provide the updated global, regional and national burden of alcohol-attributable cancer.

Approach And Results: We analysed the Global Burden of Disease Study 2021 to determine the death and age-standardised death rate (ASDR) from alcohol-attributable cancer and the change of these measures between 2000 and 2021 (reflected as annual percent change [APC]), classified by region, nation and country's developmental status, which is based on the sociodemographic index (SDI).

International Liver Transplantation Society practice guideline update on portopulmonary hypertension.

Portopulmonary hypertension (POPH), pulmonary arterial hypertension that develops in the setting of portal hypertension, has long been of significant interest to the pulmonary, cardiology, and hepatology communities. Optimal management of POPH has been challenging to define due to a lack of evidence from clinical trials regarding pulmonary arterial hypertension therapies and uncertainty regarding the role of liver transplantation (LT). Initially, the high risk of intraoperative and early post-transplant death in predominantly untreated patients with POPH tempered consideration of LT.

Global burden of HBV-related liver disease: Primary liver cancer due to chronic HBV infection increased in over one-third of countries globally from 2000 to 2021.

Backgrounds And Aims: HBV-related liver disease ranks as the seventh leading cause of mortality. Despite advances in prevention and treatment, global disparities in the burden of primary liver cancer (PLC) persist. We evaluate global trends in the prevalence, incidence, and death of HBV-related liver disease.

Alcohol-Related Liver Disease, Followed by Metabolic Dysfunction-Associated Steatotic Liver Disease, Emerges as the Fastest-Growing Aetiologies for Primary Liver Cancer in the United States.

Objective: Primary liver cancer (PLC) is projected to be the third leading cause of cancer mortality in the United States in 2040. We examine the burden of PLC in the United States, stratified by sex, state and aetiological risk factors.

Methods: Data on PLC prevalence, incidence, death and disability-adjusted life years (DALYs) were extracted from the Global Burden of Disease Study 2021.

Unmet needs in diagnosis and management of portopulmonary hypertension: How far have we reached?

Portopulmonary hypertension (POPH), a form of pulmonary artery hypertension, occurs because of portal hypertension. Pulmonary hemodynamics and right heart function are key entities that are considered when diagnosing and treating POPH. Medical management, combined with liver transplantation, offers a unique opportunity for POPH "cure"; however, transplant risk can be significant as it relates to the severity of POPH.

Neighborhood Social Determinants of Health Are Associated With Metabolic Dysfunction-associated Steatotic Liver Disease Outcomes.

Background & Aims: Significant health disparities exist in metabolic dysfunction-associated steatotic liver disease (MASLD), driven by social determinants of health (SDOH). Few studies have explored neighborhood-level SDOH in MASLD.

Methods: This is a retrospective cohort study of patients with MASLD at a multi-state healthcare institution.

Smoking and outcomes in candidates for liver transplantation: Analysis of the Pulmonary Vascular Complications of Liver Disease 2 (PVCLD2).

Patients with chronic liver disease commonly have abnormal lung function; however, the impact of smoking on outcomes in these patients is unknown. We hypothesized current or past smoking would be associated with worse survival in patients with advanced liver disease. The Pulmonary Vascular Complications in Liver Disease Study 2 (PVCLD2) was a prospective cohort of patients with advanced liver disease undergoing evaluation for liver transplantation (LT).

Mortality outcomes in individuals with MASLD versus MASLD and increased alcohol intake.

Background And Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease worldwide. A new entity termed MetALD has also been described and is defined as individuals with MASLD and increased alcohol intake. However, the natural history of MetALD compared with MASLD is unknown.

A Novel Animal Model for Pulmonary Hypertension: Lung Endothelial-Specific Deletion of in Mice.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by high blood pressure in the pulmonary arteries, which can potentially lead to heart failure over time. Previously, our lab found that endothelia-specific knockout of , encoding prolyl 4-hydroxylase-2 (PHD2), induced spontaneous pulmonary hypertension (PH). Recently, we elucidated that is a lung-specific endothelial gene using mice.

Pulmonary Complications of Portal Hypertension.

Portopulmonary hypertension (POPH), hepatopulmonary syndrome, and hepatic hydrothorax constitute significant complications of portal hypertension, with important implications for management and liver transplantation (LT) candidacy. POPH is characterized by obstruction and remodeling of the pulmonary resistance arterial bed. Hepatopulmonary syndrome is the most common pulmonary vascular disorder, characterized by intrapulmonary vascular dilatations causing impaired gas exchange.

Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: a systematic analysis from the global burden of disease study 2019.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.

General Capillary Endothelial Cells Undergo Reprogramming into Arterial Endothelial Cells in Pulmonary Hypertension through HIF-2α/Notch4 Pathway.

Pulmonary arterial hypertension (PAH) is characterized by a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling that result in right heart hypertrophy, failure, and premature death. The underlying mechanisms of loss of distal capillary endothelial cells (ECs) and obliterative vascular lesion formation remain unclear. Our recent single-cell RNA sequencing, spatial transcriptomics analysis, RNASCOPE, and immunostaining analysis showed that arterial ECs accumulation and loss of capillary ECs were evident in human PAH patients and pulmonary hypertension (PH) rodents.

Disparities among ethnic groups in mortality and outcomes among adults with MASLD: A multicenter study.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and 10%-20% occurs in lean individuals. There is little data in the literature regarding outcomes in an ethnically-diverse patient populations with MASLD. Thus, we aim to investigate the natural history and ethnic disparities of MASLD patients in a diverse population, and stratified by body mass index categories.

Single-cell and Spatial Transcriptomics Identified Fatty Acid-binding Proteins Controlling Endothelial Glycolytic and Arterial Programming in Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Single-cell RNA sequencing (scRNAseq) analysis found that both FABP4 and FABP5 were highly induced in endothelial cells (ECs) of (CKO) mice, which was also observed in pulmonary arterial ECs (PAECs) from idiopathic PAH (IPAH) patients, and in whole lungs of pulmonary hypertension (PH) rats.

E2F1 Mediates SOX17 Deficiency-Induced Pulmonary Hypertension.

Background: Rare genetic variants and genetic variation at loci in an enhancer in SOX17 (SRY-box transcription factor 17) are identified in patients with idiopathic pulmonary arterial hypertension (PAH) and PAH with congenital heart disease. However, the exact role of genetic variants or mutations in SOX17 in PAH pathogenesis has not been reported.

Methods: SOX17 expression was evaluated in the lungs and pulmonary endothelial cells (ECs) of patients with idiopathic PAH.

Rising incidence and impact of early-onset colorectal cancer in the Asia-Pacific with higher mortality in females from Southeast Asia: a global burden analysis from 2010 to 2019.

Background And Aim: Early-onset colorectal cancer (CRC) is a growing global health concern, especially in the Asia-Pacific region. However, comprehensive research on this topic from the region is lacking. Our study aims to investigate trends in early-onset CRC in Asia over 10 years, filling this research gap.

Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension.

Portopulmonary hypertension (PoPH) is a type of pulmonary vascular disease due to portal hypertension that exhibits high morbidity and mortality. The mechanisms driving disease are unknown, and transcriptional characteristics unique to the PoPH liver remain unexplored. Here, we apply single nuclear RNA sequencing to compare cirrhotic livers from patients with and without PoPH.

Fibrosis-4 Index Score Predicts Concomitant Coronary Artery Diseases Across the Spectrum of Fatty Liver Disease.

Background: 25% of US adults have nonalcoholic fatty liver disease (NAFLD). The independent association between hepatic fibrosis and cardiovascular disease remains controversial. Metabolic dysfunction-associated fatty liver disease (MAFLD) precisely characterizes hepatic steatosis.