Lazarus, Jeffrey V

Abstract Background & Aims: Alcohol is a leading global risk factor, over 200 diseases and injuries, but policy adoption varies. We updated the Alcohol Preparedness Index (API) to track global and regional policy trends from 2010–2019. Methods: Using WHO GISAH data for 141 countries, we scored five domains (policy frameworks; production/pricing/taxation; marketing/availability; drink-driving; monitoring/surveillance). The primary endpoint was % change in API. Trends were summarized by WHO region and correlates tested in adjusted regression. Results: In 2019, <25% of countries had a strong national alcohol plan and 40% had none. Production/pricing/taxation increased most (27%→78%); monitoring/surveillance reached strong levels in 47.5%. Median API increased from 57.0 [39.0–82.0] (2010) to 74.8 [58.3–83.5] (2016) and stayed above baseline in 2019 (67.8 [51.2–83.8]). Larger population predicted less API gain (β=−19.1, p<0.05); HDI and per-capita consumption did not. Conclusions: Global alcohol policy preparedness increased from 2010–2019.

Importance Metabolic dysfunction–associated steatohepatitis (MASH) represents a high, underprioritized burden among noncommunicable diseases (NCDs) and people living with type 2 diabetes (T2D). Objective To identify cost-effective management approaches to prevent, detect, and treat MASH and liver fibrosis in people living with T2D. Design, Setting, and Participants This economic evaluation consisted of a generalized cost-effectiveness analysis (GCEA) that was conducted for 12 countries (Brazil, Chile, Germany, Italy, Japan, Saudi Arabia, South Africa, Spain, Sweden, Tanzania, Thailand, and the United States), across all 6 World Health Organization (WHO) regions. A cohort state-transition model simulated liver disease development and its impact on a synthetic cohort, aged 19 years and older and living with T2D, over their lifespan across 10 liver health states. Exposures Using an 80% coverage level, 14 management approaches were compared, including screening via the Fibrosis-4 (FIB-4) test and Enhanced Liver Fibrosis (ELF) test or vibration-controlled transient elastography (VCTE) as well as treatment with pharmacological and nonpharmacological interventions. Main Outcomes and Measures The main outcomes were the average cost-effectiveness ratios (ACERs) and the incremental cost-effectiveness ratios (ICERs), which were used to construct care expansion paths by ranking the management approaches in order of cost-effectiveness. The main measures were the total incremental costs and the total incremental quality-adjusted life-years (QALYs) of each intervention. Results In this GCEA, the outcomes were evaluated with respect to country-specific willingness-to-pay thresholds. The standard of care had the lowest ACERs in 8 countries (not in Chile, Germany, Saudi Arabia, or the United States). Treatment with intensive lifestyle interventions (ILIs), after screening via ELF or VCTE, was cost-effective in all countries. ILIs and treatment with semaglutide was cost-effective in 11 countries (not in Tanzania); ILIs and treatment with resmetirom was cost-effective in 8 countries (not in Brazil, South Africa, Tanzania, or Thailand). Conclusion and Relevance In this economic evaluation, screening followed by ILIs was found to be a cost-effective management approach for MASH and liver fibrosis among people living with T2D in all countries. Screening followed by pharmacological treatment was cost-effective in most countries. These results can inform health policy decision-making and further the development of WHO recommended interventions to address NCDs.

Background: Noninvasive tests (NITs) are used to risk-stratify metabolic dysfunction–associated steatotic liver disease. The aim was to survey global patterns of real-world use of NITs. Methods: A 38-item survey was designed by the Global NASH Council. Providers were asked about risks for advanced fibrosis, which NITs (cutoff values) they use to risk-stratify liver disease, monitor progression, and which professional guidelines they follow. Results: A total of 321 participants from 43 countries completed the survey (54% hepatologists, 28% gastroenterologists, and 18% other). Of the respondents, 85% would risk-stratify patients with type 2 diabetes, obesity (82%), or abnormal liver enzymes (73%). Among NITs to rule out significant or advanced fibrosis, transient elastography (TE) and fibrosis-4 (FIB-4) were most used, followed by NAFLD Fibrosis Score, Enhanced Liver Fibrosis, and magnetic resonance elastography. The cutoffs for ruling out significant fibrosis varied considerably between practices and from guidelines, with only 50% using TE <8 kPa, 65% using FIB-4 <1.30 for age <65, and 41% using FIB-4 <2.00 for age ≥65. Similar variability was found for ruling in advanced fibrosis, where thresholds of FIB-4 ≥2.67 and TE ≥10 kPa were used by 20% and 17%, respectively. To establish advanced fibrosis, 48% would use 2 NITs while 23% would consider 1 NIT, and 17% would confirm with liver biopsy. TE was used by >75% to monitor, and 66% would monitor (intermediate or high risk) annually. Finally, 65% follow professional guideline recommendations regarding NITs. Conclusions: In clinical practice, there is variability in NIT use and their thresholds. Additionally, there is suboptimal adherence to professional societies’ guidelines.

Background and Aims: Screening for diseases can have psychological impacts, such as anxiety, and requires acceptability from the population to be effective. This study examined the perspectives on the benefits and harms of screening for metabolic dysfunction–associated steatotic liver disease (MASLD) among the general population to optimize screening practices. Approach and Results: A survey was sent to participants enrolled between 2020 and 2024 in a prospective MASLD screening study in Olmsted County, MN. The survey assessed participants' perceived anxiety, stigma, quality of life, preferred screening methods, financial concerns, and lifestyle impacts following screening and diagnosis. Of the 461 participants, 342 (74%) completed the survey. Overall, 14% of participants reported screening-related anxiety, and 14% were concerned about disclosing a potential MASLD diagnosis to others. Among those without a MASLD diagnosis, 99% felt reassured about their liver health, 48% reported an improved quality of life, and 25% made lifestyle changes pertaining to their diet, alcohol use, and physical activity. Of the 77 participants diagnosed with MASLD, 52% experienced some anxiety about their new diagnosis; however, 95% and 97% considered it important to receive an early MASLD diagnosis to mitigate the risk for cirrhosis and cardiovascular disease, respectively. Notably, 79% of diagnosed participants found the diagnosis beneficial in adopting healthier habits, with 30% achieving a >10% weight loss after screening. Conclusion: This population-based survey demonstrates that the perceived benefits of proactive MASLD screening, such as increased awareness, lifestyle changes, and early diagnosis, outweigh the harms. These findings highlight the importance of early screening through patient-centered protocols to improve health outcomes.

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: Metabolic dysfunction–associated steatotic liver disease management guidelines have been published worldwide; we aimed to summarize, categorize, and compare their lifestyle intervention recommendations. Approach and Results: We searched metabolic dysfunction–associated steatotic liver disease/NAFLD management guidelines published between January 1, 2013, and June 31, 2024, through databases including PubMed/MEDLINE, Cochrane, and CINAHL. In total, 35 qualifying guidelines were included in the final analysis. Guideline recommendations were categorized into 5 domains (ie, weight reduction goals, physical activity, nutrition, alcohol, and tobacco smoking) and were ranked based on how frequently they appeared. A recommendation was defined as widely adopted if recommended in ≥24 (≥66.6%) of the guidelines. These included increasing physical activity; reducing body weight by 7%–10% to improve steatohepatitis and/or fibrosis; restricting caloric intake; undertaking 150–300 or 75–150 minutes/week of moderate or vigorous-intensity physical activity, respectively; and decreasing consumption of commercially produced fructose. The least mentioned topics, in ≤9 of the guidelines, evaluated environmental determinants of health, mental health, referring patients for psychological or cognitive behavioral therapy, using digital health interventions, and assessing patients’ social determinants of health. Conclusions: Most guidelines recommend weight reduction through physical activity and improving nutrition, as these have proven positive effects on health outcomes when sustained. However, gaps regarding mental health and the social and environmental determinants of metabolic dysfunction–associated steatotic liver disease were found. To optimize behavioral modifications and treatment, we recommend carrying out studies that will provide further evidence on social support, environmental factors, and mental health, as well as further exploring digital health interventions.

Abstract Background Outcomes in alcohol‐associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown. Methods We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis. Results Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable‐adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non‐Hispanic White interviewees (OR: 1.4, 95% CI: 1.1–1.8 and OR: 1.5 95% CI:1.1–2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6–.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73–.94). Finally, a multivariate competing‐risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6–.8) along with female Asian population (HR: .40, 95% CI: .26–.62). Conclusions After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.

Abstract Background and Aims Non‐invasive tests (NITs) are underutilized for diagnosis and risk stratification in metabolic dysfunction‐associated steatotic liver disease (MASLD), despite good accuracy. This study aimed to identify challenges and barriers to the use of NITs in clinical practice. Methods We conducted a qualitative exploratory study in Germany, Italy, United Kingdom and United States. Phase 1 participants (primary care physicians, hepatologists, diabetologists, researchers, healthcare administrators, payers and patient advocates; n = 29) were interviewed. Phase 2 participants (experts in MASLD; n = 8) took part in a group discussion to validate and expand on Phase 1 findings. Finally, we triangulated perspectives in a hybrid deductive/inductive thematic analysis. Results Four themes hindering the use of NITs emerged: (1) limited knowledge and awareness; (2) unclear referral pathways for patients affected by liver conditions; (3) uncertainty over the value of NITs in monitoring and managing liver diseases; and (4) challenges justifying system‐level reimbursement. Through these themes, participants perceived a stigma associated with liver diseases, and primary care physicians generally lacked awareness, adequate knowledge and skills to use recommended NITs. We identified uncertainties over the results of NITs, specifically to guide lifestyle intervention or to identify patients that should be referred to a specialist. Participants indicated an ongoing need for research and development to improve the prognostic value of NITs and communicating their cost‐effectiveness to payers. Conclusions This qualitative study suggests that use of NITs for MASLD is limited due to several individual and system‐level barriers. Multi‐level interventions are likely required to address these barriers.