Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with T2D and MASLD.

Background & Aims: Lanifibranor is a pan-PPAR agonist that improves glucose/lipid metabolism and reverses steatohepatitis and fibrosis in adults with MASH. We tested its effect on insulin resistance at the level of different target tissues in relationship to change in intrahepatic triglyceride (IHTG) content.

Methods: This phase 2, single center, study randomized (1:1) 38 patients with T2D and MASLD to receive lanifibranor 800 mg or placebo for 24 weeks.

Interdisciplinary perspectives on the co-management of metabolic dysfunction-associated steatotic liver disease and coronary artery disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a public health threat as it affects approximately 38% of the adult population worldwide, with its prevalence rising in step with that of obesity and type 2 diabetes. Beyond the implications of MASLD for liver health, it is also associated with cardiovascular and vascular dysfunction. Although the many shared risk factors and common metabolic milieu might indicate that cardiovascular disease and MASLD are discrete outcomes from common systemic pathogeneses, a growing body of evidence has identified a potential causal relationship between MASLD and coronary artery disease, which is the leading cause of morbidity and mortality in people with MASLD and all-cause mortality worldwide.

Obesity increases the risk of hepatic fibrosis in young adults with type 2 diabetes mellitus: the need to screen.

Objective: The objective of this study was to determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in young compared with older adults.

Methods: Individuals (n = 1420) with (63%) and without type 2 diabetes mellitus (T2D; 37%) who attended internal medicine clinics and did not have a known history of MASLD underwent laboratory evaluation and transient elastography to assess for hepatic steatosis and fibrosis. Magnetic resonance elastography and liver biopsy were recommended when indicated.

Detecting altered hepatic lipid oxidation by MRI in an animal model of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030.

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL.

Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD.

Insulin resistance is an integral feature of MASLD even in the presence of PNPLA3 variants.

Background & Aims: It has been postulated that carriers of PNPLA3 I148M (CG [Ile/Met] or GG [Met/Met]) develop metabolic dysfunction-associated steatotic liver disease (MASLD) in the absence of insulin resistance or metabolic syndrome. However, the relationship between insulin resistance and MASLD according to the allele has not been carefully assessed.

Methods: A total of 204 participants were recruited and underwent genotyping, an oral glucose tolerance test, liver proton magnetic resonance spectroscopy and percutaneous liver biopsy if diagnosed with MASLD.

Guideline-based management of metabolic dysfunction-associated steatotic liver disease in the primary care setting.

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. Primary care providers play a critical role in the screening, diagnosis, and management of MASLD and/or metabolic dysfunction-associated steatohepatitis (MASH), though they can face challenges in this setting, particularly where healthcare resources are limited and barriers to care exist. To address these challenges, several guidelines have been developed to provide evidence-based recommendations for the clinical assessment and management of patients with MASLD/MASH.

Making Sense of the Nonalcoholic Fatty Liver Disease Clinical Practice Guidelines: What Clinicians Need to Know.

Standards of care summarized in clinical practice guidelines for nonalcoholic fatty liver disease (NAFLD) offer clinicians a streamlined diagnostic and management approach based on the best available evidence. These recommendations have changed a great deal in recent years; today, there is a clear focus on screening for the early identification and risk stratification of patients at high risk of steatohepatitis and clinically significant fibrosis to promote timely referrals to specialty care when needed. This article reviews and provides the rationale for current guidelines for NAFLD screening, diagnosis, treatment, and monitoring and addresses barriers to providing evidence-based NAFLD care and how to overcome them.

Role of Insulin Resistance in the Development of Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: From Bench to Patient Care.

Insulin resistance is implicated in both the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and its progression from steatosis to steatohepatitis, cirrhosis, and even hepatocellular carcinoma, which is known to be more common in people with type 2 diabetes. This article reviews the role of insulin resistance in the metabolic dysfunction observed in obesity, type 2 diabetes, atherogenic dyslipidemia, and hypertension and how it is a driver of the natural history of NAFLD by promoting glucotoxicity and lipotoxicity. The authors also review the genetic and environmental factors that stimulate steatohepatitis and fibrosis progression and their relationship with cardiovascular disease and summarize guidelines supporting the treatment of NAFLD with diabetes medications that reduce insulin resistance, such as pioglitazone or glucagon-like peptide 1 receptor agonists.

Pharmacological Approaches to Nonalcoholic Fatty Liver Disease: Current and Future Therapies.

Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), can promote the development of cirrhosis, hepatocellular carcinoma, cardiovascular disease, and type 2 diabetes. Similarly, type 2 diabetes confers the greatest risk for the development of NASH, especially when associated with obesity. Although lifestyle changes are critical to success, early implementation of pharmacological treatments for obesity and type 2 diabetes are essential to treat NASH and avoid disease progression.

Implementation of a liver health check in people with type 2 diabetes.

As morbidity and mortality related to potentially preventable liver diseases are on the rise globally, early detection of liver fibrosis offers a window of opportunity to prevent disease progression. Early detection of non-alcoholic fatty liver disease allows for initiation and reinforcement of guidance on bodyweight management, risk stratification for advanced liver fibrosis, and treatment optimisation of diabetes and other metabolic complications. Identification of alcohol-related liver disease provides the opportunity to support patients with detoxification and abstinence programmes.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers.

Methods: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey.

Artificial intelligence-assisted digital pathology for non-alcoholic steatohepatitis: current status and future directions.

The worldwide prevalence of non-alcoholic steatohepatitis (NASH) is increasing, causing a significant medical burden, but no approved therapeutics are currently available. NASH drug development requires histological analysis of liver biopsies by expert pathologists for trial enrolment and efficacy assessment, which can be hindered by multiple issues including sample heterogeneity, inter-reader and intra-reader variability, and ordinal scoring systems. Consequently, there is a high unmet need for accurate, reproducible, quantitative, and automated methods to assist pathologists with histological analysis to improve the precision around treatment and efficacy assessment.

Impact of Type 2 Diabetes on the Outcomes of Solid Organ Transplantations in the U.S.: Data From a National Registry.

Objective: Type 2 diabetes (T2D) is a major driver of chronic diseases around the globe. The aim was to assess the impact of T2D on the outcomes of solid organ transplantations.

Research Design And Methods: We used the Scientific Registry of Transplant Recipients from 2006 to 2021 to collect data for all patients age ≥18 years who received a lung, heart, liver, or kidney transplant in the U.

A global action agenda for turning the tide on fatty liver disease.

Background And Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care.

Approach And Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice.

Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF).

Background: Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH.

Methods: We included derivation (n = 790) and validation (n = 565) cohorts from international tertiary centers.