Cusi, Kenneth

Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease (NAFLD), is a growing but often unrecognized medical problem for people with diabetes (particularly type 2 diabetes, especially when associated with obesity). Liver health has not been at the forefront of complications tracked for disease prevention, as traditionally done for diabetic retinopathy, nephropathy, or neuropathy. However, liver steatosis affects approximately two out of three people with type 2 diabetes and places them at an increased risk for metabolic dysfunction–associated steatohepatitis (MASH), cirrhosis, hepatocellular carcinoma (HCC), and overall liver-related mortality. MASLD is also associated with extrahepatic cancers, atherosclerotic cardiovascular disease, and progression from prediabetes to type 2 diabetes and negatively impacts health-related quality of life. However, most individuals and their health care professionals remain unaware of the severe hepatic or extrahepatic health risks associated with MASLD and the need for early identification. In recognition of this knowledge gap and the rising prevalence of MASLD, this consensus report is a call to action to screen for liver fibrosis and risk stratify people with prediabetes or type 2 diabetes, in particular if obesity is also present. This consensus report explains the rationale for the recent MASLD nomenclature change, how to best risk stratify, current treatment and long-term monitoring options, the value of an interprofessional approach to disease management, and the impact of alcohol intake on liver health. More awareness about the health risks associated with MASLD and broad adoption of screening for liver fibrosis as a new standard of care hold promise for a future without cirrhosis for people with prediabetes and type 2 diabetes.

ABSTRACT 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. MASLD poses a significant global health challenge with its rising prevalence, placing a substantial burden on healthcare systems, impacts patient well‐being and incurs significant economic costs. Addressing MASLD requires a comprehensive understanding of its interconnected factors, including its prevalence, healthcare burden and economic implications. Lack of awareness, imprecise non‐invasive diagnostic methods and ineffective preventive interventions are core components of the MASLD‐related problem. Aim The aim of this article was to summarise the global burden of MASLD from the payer's perspective. Methods We carried out a review of the global comprehensive burden of MASLD. These topics led to discussions and insights by an expert panel during the 7th Metabolic Continuum Roundtable meeting, which took place in November 2023. This meeting focused on the burden, patient‐reported outcomes and health economics, from payor and societal perspectives, and aimed to identify opportunities for improving patient care, optimise resource allocation and mitigate the overall impact on individuals and society related to MASLD. During the roundtable, an emphasis emerged on the need for greater awareness and strategic deployment of diagnostic, therapeutic and preventative measures to address MASLD effectively. Conclusion The global burden of MASLD is high and growing. Prioritising the prevention of metabolic dysregulation and timely therapeutic interventions can yield a holistic strategy to combat MASLD, its progression and potentially lower disease costs. Trial Registration: NCT06309992

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. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of “agree” responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% “agree”). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

Abstract Purpose Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM). Methods Subjects with new-onset DM (<3 years’ duration) in the setting of PDAC (PDAC-DM, n = 28), CP (CP-DM, n = 38), or T2DM (n = 99) completed a standardized mixed meal tolerance test, then serum PP concentrations were subsequently measured at a central laboratory. Two-way comparisons of PP concentrations between groups were performed using Wilcoxon rank-sum test and analysis of covariance while adjusting for age, sex, and body mass index. Results The fasting PP concentration was lower in both the PDAC-DM and CP-DM groups than in the T2DM group (P = 0.03 and <0.01, respectively). The fold change in PP at 15 minutes following meal stimulation was significantly lower in the PDAC-DM (median, 1.869) and CP-DM (1.813) groups compared with T2DM (3.283; P < 0.01 for both comparisons). The area under the curve of PP concentration was significantly lower in both the PDAC-DM and CP-DM groups than in T2DM regardless of the interval used for calculation and remained significant after adjustments. Conclusions Fasting PP concentrations and the response to meal stimulation are reduced in new-onset DM associated with PDAC or CP compared with T2DM. These findings support further investigations into the use of PP concentrations to characterize pancreatogenic DM and to understand the pathophysiological role in exocrine pancreatic diseases (NCT03460769).