Disparities in Health Care in Patients With Chronic Liver Disease.

Chronic liver disease (CLD) is increasing in prevalence worldwide. CLD has significant associated morbidity and mortality, including a negative impact on health-related quality of life (HRQOL), progression to cirrhosis, development of hepatocellular carcinoma (HCC), and need for liver transplantation. CLD disproportionately impacts racial, ethnic, sexual, and gender minorities.

Metabolic dysfunction-associated steatotic liver disease in adults.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the umbrella term that comprises metabolic dysfunction-associated steatotic liver, or isolated hepatic steatosis, through to metabolic dysfunction-associated steatohepatitis, the progressive necroinflammatory disease form that can progress to fibrosis, cirrhosis and hepatocellular carcinoma. MASLD is estimated to affect more than one-third of adults worldwide. MASLD is closely associated with insulin resistance, obesity, gut microbial dysbiosis and genetic risk factors.

PNPLA3 I148M and Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. With the widespread implementation of HBV vaccination and the availability of highly effective antiviral therapies, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC has proportionally increased. Notably, up to 20%-30% of MASLD-related HCC cases develop in the absence of overt cirrhosis.

Addressing the High and Rising Global Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH): From the Growing Prevalence to Payors' Perspective.

Background: The continuum of metabolic syndrome encompasses a spectrum of dysfunctions impacting obesity-linked insulin resistance, glucose homeostasis, lipid metabolism and pro-inflammatory immune responses. The global prevalence of metabolic diseases, including diabetes, chronic liver disease, cardiometabolic disease and kidney disease, has surged in recent decades, contributing significantly to population mortality. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a leading cause of liver disease worldwide.

Comparison Between Dynamic Models for Predicting Response to Corticosteroids in Alcohol-Associated Hepatitis: A Global Cohort Study.

Several dynamic models predict mortality and corticosteroid response in alcohol-associated hepatitis (AH), yet no consensus exists on the most effective model. This study aimed to assess predictive models for corticosteroid response and short-term mortality in severe AH within a global cohort. We conducted a multi-national study of patients with severe AH treated with corticosteroids for at least 7 days, enrolled between 2009 and 2019.

Management of alcohol use disorder: a gastroenterology and hepatology-focused perspective.

Alcohol use disorder is a prevalent and major but preventable cause of morbidity and mortality worldwide, causing several important health consequences, including chronic liver disease. Despite its substantial effects, most clinicians do not adequately assess alcohol intake in clinical practice, and there are several barriers to providing integrated management to patients with alcohol use disorder. Standardised questionnaires, such as the Alcohol Use Identification Test (AUDIT), can facilitate the identification of individuals at risk of alcohol use disorder, and alcohol biomarkers such as phosphatidylethanol aid in quantifying levels of alcohol consumption.

Clinical Trial to Assess the Safety and Tolerability of Anti-IL 23 Monoclonal Antibody Guselkumab in Patients With Alcohol-Associated Liver Disease.

Background: There are no FDA-approved therapies for alcohol-associated liver disease (ALD). Preclinical studies indicate that blocking IL-23/IL-17 signalling may reverse liver injury. Guselkumab, an IL-23-specific antibody approved for psoriasis, may be beneficial for ALD.

The Lipidomic Profile Discriminates Between MASLD and MetALD.

Background: The recent consensus statement redefined steatotic liver diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction and alcohol-related liver disease (MetALD) now represent distinct disease entities. However, biomarkers that differentiate MASLD and MetALD remain largely unknown.

The Global Burden of Cirrhosis and Other Chronic Liver Diseases in 2021.

Background And Aim: The burden of cirrhosis and other chronic liver diseases has changed in recent years due to shifts in the contributing aetiologies. We estimated the burden of cirrhosis and other chronic liver diseases, including etiological and regional differences, across 204 countries and territories from 2010 to 2021.

Approach And Results: We analysed temporal trends in the burden of cirrhosis and other chronic liver diseases utilising data from the Global Burden of Disease Study 2021.

Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis.

Background And Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. With the advent of multiple therapeutic targets in late-phase clinical drug development for MASH, there is a knowledge gap to better understand the comparative efficacy of various pharmacological agents. We conducted an updated network meta-analysis to evaluate the relative rank-order of the different pharmacological agents for both fibrosis regression and MASH resolution.

Colorectal Cancer Incidence in Steatotic Liver Disease (MASLD, MetALD, and ALD).

Background And Aims: Obesity and alcohol consumption are established risk factors for colorectal cancer (CRC). Recently, a multisociety consensus group has introduced a new classification for steatotic liver disease (SLD), which encompasses metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD). However, the risk of developing CRC in each of these SLD subgroups is unknown.

Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis.

No therapy has been shown to reduce the risk of major adverse liver outcomes (MALO) in patients with cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) observational study compared the effects of metabolic surgery and nonsurgical treatment in patients with obesity and compensated histologically proven MASH-related cirrhosis. Using a doubly robust estimation methodology to balance key baseline characteristics between groups, the time-to-incident MALO was compared between 62 patients (68% female) who underwent metabolic surgery and 106 nonsurgical controls (71% female), with a mean follow-up of 10.

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.

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.

Neurogastroenterology and motility disorders in patients with cirrhosis.

Neurogastroenterology and motility disorders are complex gastrointestinal conditions that are prevalent worldwide, particularly affecting women and younger individuals. These conditions significantly impact the quality of life of people suffering from them. There is increasing evidence linking these disorders to cirrhosis, with a higher prevalence compared to the general population.