Unraveling Mechanisms of Genetic Risks in Metabolic Dysfunction-Associated Steatotic Liver Diseases: A Pathway to Precision Medicine.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem, affecting ∼1 billion people. This condition is well established to have a heritable component with strong familial clustering. With the extraordinary breakthroughs in genetic research techniques coupled with their application to large-scale biobanks, the field of genetics in MASLD has expanded rapidly.

Head-to-Head Comparison Between Phosphatidylethanol Versus Indirect Alcohol Biomarkers for Diagnosis of MetALD Versus MASLD: A Prospective Study.

Background: The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity.

Aims: To assess the diagnostic accuracy of PEth for differentiating metabolic dysfunction and alcohol-associated liver disease (MetALD) from metabolic dysfunction-associated steatotic liver disease (MASLD) in a large, population-based, prospective, multiethnic cohort of individuals with overweight or obesity.

Discovery of robust and highly specific microbiome signatures of non-alcoholic fatty liver disease.

Background: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) with a global prevalence of 30% is multifactorial and the involvement of gut bacteria has been recently proposed. However, finding robust bacterial signatures of NAFLD has been a great challenge, mainly due to its co-occurrence with other metabolic diseases.

Results: Here, we collected public metagenomic data and integrated the taxonomy profiles with in silico generated community metabolic outputs, and detailed clinical data, of 1206 Chinese subjects w/wo metabolic diseases, including NAFLD (obese and lean), obesity, T2D, hypertension, and atherosclerosis.

AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

Current Burden of Lean Metabolic Dysfunction-Associated Steatotic Liver Disease Among US Adults, 2017-2023.

Our study investigated the prevalence of lean steatotic liver disease (SLD) and its subcategories, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-related and alcohol-related SLD (MetALD), and alcohol-related liver disease (ALD) among lean adults in the US. Analysing data from 2965 lean adults (≥ 18 years) from the National Health and Nutrition Examination Survey (2017-2023), we found the age-adjusted prevalence of lean SLD to be 12.8%.

Extracorporeal Membrane Oxygenation in Children with Pulmonary Atresia and Intact Ventricular Septum: Mortality and Associated Outcomes.

Data on outcomes of extracorporeal membrane oxygenation (ECMO) are limited in patients with pulmonary atresia intact ventricular septum (PAIVS). The objective of this study was to describe the use of ECMO and the associated outcomes in patients with PAIVS. We retrospectively reviewed neonates with PAIVS who received ECMO between 2009 and 2019 in 19 US hospitals affiliated with the Collaborative Research for the Pediatric Cardiac Intensive Care Society (CoRe-PCICS).

Global Epidemiology of Alcohol-Related Liver Disease, Liver Cancer, and Alcohol Use Disorder, 2000-2021.

Background/aims: Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000-2021.

Methods: We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database.

Primary Care Screening for Nonalcoholic Fatty Liver Disease Among People With HIV in the United States: A Real-World Provider Survey.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people with HIV (PWH) and increases the risk of hepatic fibrosis and hepatocellular carcinoma. We sent an online survey to providers of the American Academy of HIV Medicine. Of respondents (n = 214, 8% response rate), 65% reported screening for NAFLD in PWH, with 28% routinely screening all patients.

Effects of Pemafibrate on LDL-C and Related Lipid Markers in Patients with MASLD: A Sub-Analysis of the PEMA-FL Study.

Aim: In the PEMA-FL study in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), pemafibrate was shown to significantly decrease low-density lipoprotein cholesterol (LDL-C) levels. We aimed to investigate the mechanisms of pemafibrate-induced LDL-C reduction in patients with MASLD by conducting an additional sub-analysis of the PEMA-FL study.

Methods: The PEMA-FL study randomized 118 patients with MASLD to receive pemafibrate or placebo for 72 weeks.

Epinephrine Versus Dopamine in Children, What Is the Current Evidence and What Do We Need? A Systematic Review and Meta-analysis.

Introduction: Pediatric patients often receive vasoactive agents following cardiothoracic surgery or when in shock. The use of vasoactive agents varies between different settings and has largely changed because of anecdotal observations or small observational studies. Although vasoactive agents are frequently used, there are limited studies in pediatric populations comparing them to one another.

Improving process aspect of oral examination as assessment tool in undergraduate biochemistry by introducing structured oral examination: an observational study in India based on a survey among stakeholders.

Purpose: The traditional method of oral examination, though a good tool for assessing the depth and breadth of student's knowledge, has its shortcomings. A variable number of questions with variable difficulty levels by different examiners with different expectations can introduce bias in scores. The process aspect of oral examinations of first-year undergraduate medical students was improved by structuring them and by creating uniformity in the number, time, and difficulty level of questions for assessment, and feedback was taken regarding its acceptance as an improved tool of assessment.

Targeting PNPLA3 to Treat MASH and MASH Related Fibrosis and Cirrhosis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by metabolic triggers and genetic predisposition. Among the genetic MASLD risk variants identified today, the common PNPLA3 148M variant exerts the largest effect size of MASLD heritability. The PNPLA3 148M protein is causatively linked to the development of liver steatosis, inflammation and fibrosis in experimental studies and is therefore an appealing target for therapeutic approaches to treat this disease.

Common arterial trunk with pulmonary atresia.

We report two congenitally malformed hearts found at autopsy to have common arterial trunk and pulmonary atresia. Both exhibited usual atrial arrangement, along with concordant atrioventricular connections. In one case, the common arterial trunk arose predominantly from the right ventricle, while the other had a balanced commitment.

A blood-based biomarker panel for non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis.

The current diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form, metabolic dysfunction-associated steatohepatitis (MASH), is suboptimal. Here, we recruited 700 individuals, including 184 from Hong Kong as a discovery cohort and 516 from San Diego, Wenzhou, and Hong Kong as three validation cohorts. A panel of 3 parameters (C-X-C motif chemokine ligand 10 [CXCL10], cytokeratin 18 fragments M30 [CK-18], and adjusted body mass index [BMI]) was formulated (termed N3-MASH), which discriminated patients with MASLD from healthy controls with an area under the receiver operating characteristic (AUROC) of 0.