Alcohol and Metabolic Syndrome Interaction.

Alcohol-related liver disease and metabolic-dysfunction-associated steatotic liver disease are the most common causes of chronic liver disease. Globally, alcohol intake, and metabolic syndrome driven by excessive caloric intake and sedentary lifestyle have steadily increased over the past decades. Given the high prevalence rates of both excessive alcohol consumption and components of metabolic syndrome, both can frequently coexist in the same individuals and impact their lives. In this article, we review the impact of alcohol and metabolic syndrome on liver-related outcomes.

Exploring Biomarkers in Nonalcoholic Fatty Liver Disease Among Individuals With Type 2 Diabetes Mellitus.

Integrating biomarkers into a comprehensive strategy is crucial for precise patient management, especially considering the significant healthcare costs associated with diseases. Current studies emphasize the urgent need for a paradigm shift in conceptualizing nonalcoholic fatty liver disease (NAFLD), now renamed metabolic dysfunction-associated steatotic liver disease (MASLD). Biomarkers are emerging as indispensable tools for accurate diagnosis, risk stratification, and monitoring disease progression. This review classifies biomarkers into conventional and novel categories, such as lipids, insulin resistance, hepatic function, and cutting-edge imaging/omics, and evaluates their potential to transform the approach to MASLD among individuals with type 2 diabetes mellitus (T2D). It focuses on the critical role of biomarkers in early MASLD detection, enhancing predictive accuracy, and discerning responses to interventions (pharmacological or lifestyle modifications). Amid this discussion, the complexities of the relationship between T2D and MASLD are explored, considering factors like age, gender, genetics, ethnicity, and socioeconomic background. Biomarkers enhance the effectiveness of interventions and support global initiatives to reduce the burden of MASLD, thereby improving public health outcomes. This review recognizes the promising potential of biomarkers for diagnostic precision while candidly addressing the challenges in implementing these advancements in clinical practice. The transformative role of biomarkers emerges as a central theme, promising to reshape our understanding of disease trajectories, prognosis, and the customization of personalized therapeutic strategies for improved patient outcomes. From a future perspective, identifying early-stage biomarkers, understanding environmental impact through exposomes, and applying a multiomics approach may reveal additional insight into MASLD development.

Pharmaco-Economic Assessment of Screening Strategies for High-Risk MASLD in Primary Care.

BACKGROUND AND AIMS: Several scientific associations recommend a sequential combination of non-invasive tests (NITs) to identify high-risk MASLD patients but their cost-effectiveness is unknown. METHODS: A cost-utility model was developed to assess the incremental cost-effectiveness ratio (ICER) of recommended screening strategies for patients with clinically suspected MASLD, specifically those with type 2 diabetes (T2D) and obesity with multiple cardiometabolic risk factors which will be initiated in primary care. Six screening strategies were assessed, using either vibration-controlled transient elastography (VCTE) or the enhanced liver fibrosis (ELF) test as a second-line test following an initial Fibrosis-4 (FIB-4) assessment as the first line NIT. The model included treatment effects of resmetirom for metabolic dysfunction-associated steatohepatitis (MASH) patients with F2 or F3 fibrosis. RESULTS: All screening strategies for high-risk MASLD in US incurred additional costs compared to no screening, ranging from $13 587 to $14 730 per patient with T2D and $14 274 to $15 661 per patient with obesity. However, screening reduced long-term costs, ranging from $22 150 to $22 279 per patient with T2D and $13 704 to $13 705 per patient with obesity, compared to $24 221 and $14 956 for no screening, respectively. ICERs ranged from $26 913 to $27 884 per QALY for T2D patients and $23 265 to $24 992 per QALY for patients with obesity. While ICERs were influenced by VCTE availability, they remained cost-effective when using ELF as the second-line test. Our findings remain robust across a range of key parameters. CONCLUSIONS: Screening for high-risk MASLD is cost-effective according to recent guidelines. Implementing these screening strategies in primary care should be considered.

Knowledge about metabolic dysfunction-associated steatotic liver disease among the medical professionals from countries in the MENA region.

INTRODUCTION AND OBJECTIVES: Given the substantial burden of metabolic dysfunction-associated steatotic liver disease (MASLD), there is an urgent need to assess knowledge and awareness levels among physicians. We assessed MASLD knowledge among healthcare providers from Saudi Arabia, Egypt, and Türkiye. MATERIALS AND METHODS: Two global surveys containing 54-59 items assessed awareness and knowledge of MASLD/NAFLD- one was for hepatologists and gastroenterologists, and the second was for non-specialists (e.g. endocrinologists, primary care providers [PCPs], and other healthcare professionals). Data were collected using an electronic data collection form. Knowledge scores and variables associated with higher knowledge scores were compared across all specialties. RESULTS: A total of 584 physicians completed the survey (126 hepatologists, 178 gastroenterologists (GEs), 38 endocrinologists, 242 PCPs/others). Practice guidelines were the primary source for knowledge across all specialties (43-51%), then conferences (24-31%) except PCPs/others who selected the internet as the second common source (25%). Adherence to societal guidelines varied by specialty (81-84% of specialists vs 38-51% of non-specialists). Hepatologists and GEs showed similar mean knowledge scores (51-72% correct answers across three knowledge domains, p > 0.05); endocrinologists outperformed PCPs/others in knowledge scores in all knowledge domains, including Epidemiology/Pathogenesis (72% vs. 60%), Diagnostics (73% vs. 67%), and Treatment (78% vs. 67%) (all p < 0.01). Hospital-based practice and seeing a greater number of patients with MASLD/NAFLD were identified as independent predictors of higher knowledge scores among specialists (both p < 0.05). CONCLUSIONS: A knowledge gap in the identification, diagnosis, and management of MASLD/NAFLD was found despite the growing burden of MASLD/NAFLD in Saudi Arabia, Egypt, and Türkiye. Education to increase awareness is needed.

The work environment and hospitalist work well-being and burnout.

BACKGROUND: Hospital medicine is the largest growing specialty in the United States. It is important to understand factors that are related to burnout and work well-being (WWB), both predictors of workforce retention. OBJECTIVE: To examine the relationship between work environment factors and hospitalist burnout and WWB. METHODS: An online cross-sectional survey was completed by hospitalists in July-October 2020. Burnout was assessed using the Mini-Z burnout scale and the Abbreviated Maslach Burnout Inventory. WWB was assessed using the Work Well-Being Scale. Work structure variables included hours worked per week, frustration at work, safety level of clinical workload, lack of control over schedule, lack of control over daily work, continuity of patient care, and ability to optimize license. The current desire to practice medicine was also examined. RESULTS: Eight-eight hospitalists participated. There were statistically significant differences between levels of safety of workload (F(2,85) = 9.70, p = <.005), frustration at work (F(2,85) = 12.29, p = <.005), control over schedule (F(2,85) = 3.17, p = .04), control over daily work (F(2,85) = 6.17, p = .003), and desire to practice medicine (F(2,85) = 42.34, p = <.005) with WWB. There were statistically significant associations between the presence of burnout and the safety of workload (χ2 = 8.167, p = .017), frustration at work (χ2 = 15.29, p = .005), control over daily work (χ2 = 12.48, p = .002), and desire to practice medicine (χ2 = 7.12, p = .03). WWB was positively associated with years as a hospitalist (r = .249, p = .02)). CONCLUSION: Work environment factors are associated with WWB and burnout. Modifiable work environment factors may offer a point of intervention for reducing burnout and enhancing WWB among hospitalists.

Changes in mortality due to Chronic Liver Diseases (CLD) during the COVID-19 pandemic: Data from the United States' National Vital Statistics System.

INTRODUCTION: We assessed chronic liver disease (CLD)-related mortality in the U.S. using death data (2011-2021) obtained from National Vital Statistics System (NVSS). The average annual percentage change (AAPC) from the models selected by Joinpoint regression analysis over the pre-pandemic (2011-2019) and the 2019-2021 were reported because non-linear trend in death rates were observed over the 2011-2021. Liver-specific death was defined as an underlying cause of death and Chronic liver disease (CLD)-related death was defined as any cause of death. During the pre-pandemic, age-standardized HCC- and cirrhosis-specific death rates were annually increased by AAPC = +1.18% (95% confidence interval, 0.34% to 2.03%) and AAPC = +1.95% (1.56% to 2.35%). In contrast, during the 2019-2021, the AAPC in age-standardized cirrhosis-specific death rate (per 100,000) accelerated by up to AAPC +11.25% (15.23 in 2019 to 18.86 in 2021) whereas that in age-standardized HCC-specific death rate slowed to -0.39 (-1.32% to 0.54%) (3.86 in 2019 to 3.84 in 2021). Compared to HCC-specific deaths, cirrhosis-specific deaths were more likely to be non-Hispanic white (72.4% vs. 62.0%) and non-Hispanic American Indian and Alaska native (AIAN) (2.2% vs. 1.1%) and have NAFLD (45.3% vs. 12.5%) and ALD (27.6% vs. 22.0%). During the 2019-2021, the age-standardized HCV- and HBV-related death rate stabilized, whereas the age-standardized NAFLD- and ALD-related deaths rate increased to 20.16 in 2021 (AAPC = +12.13% [7.76% to 16.68%]) and to 14.95 in 2021 (AAPC = +18.30% [13.76% to 23.03%]), which were in contrast to much smaller incremental increases during the pre-pandemic (AAPC = +1.82% [1.29% to 2.35%] and AAPC = +4.54% [3.97% to 5.11%]), respectively). The most pronounced rise in the age-standardized NAFLD-related death rates during the pandemic was observed among AIAN (AAPC = +25.38%), followed by non-Hispanic White female (AAPC = +14.28%), whereas the age-standardized ALD-related death rates during the pandemic were highest among AIAN (AAPC = +40.65%), followed by non-Hispanic Black female (AAPC = +26.79%). CONCLUSIONS: COVID-19 pandemic had a major negative impact on cirrhosis-specific and CLD-related mortality in the U.S. with significant racial and gender disparities.

Health-related quality of life (HRQL) assessments in a 52-week, double-blind, randomized, placebo-controlled phase III study of resmetirom (MGL-3196) in patients with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis.

BACKGROUND AND AIMS: Resmetirom, liver-directed thyroid-hormone receptor-ß agonist, received approval for metabolic dysfunction-associated steatohepatitis (MASH) treatment. We assessed health-related quality of life (HRQL) in patients with MASH treated with resmetirom. APPROACH AND RESULTS: Patients with MASH/NASH without cirrhosis and with confirmed/suspected fibrosis were enrolled in a 54-month double-blind randomized placebo-controlled phase III clinical trial with serial biopsy assessments at baseline and week 52 (MAESTRO-NASH, NCT03900429). HRQL was assessed using Chronic Liver Disease Questionnaire-NASH (CLDQ-NAFLD) and Liver Disease Quality of Life (LDQOL). Baseline HRQL score changes by treatment group (resmetirom 80 mg, resmetirom 100 mg, or placebo) and histological response (improvement of fibrosis without worsening of NAS or resolution of MASH/NASH without worsening of fibrosis) were compared after 52 weeks. Included were 966 intention-to-treat patients: 323 received resmetirom 100 mg, 322 resmetirom 80 mg, and 321 placebo. By weeks 24 and 52, patients receiving 80 or 100 mg resmetirom experienced HRQL improvement in CLDQ-NAFLD Worry domain (mean +0.21 to +0.24, p < 0.05). At week 52, subjects who met histologic endpoints after treatment with resmetirom (100 mg and 80 mg pooled) experienced HRQL improvement in CLDQ-NAFLD Worry +0.46 (41% met minimal clinically important difference [MCID]), LDQOL domains: Role Emotional +3.0 (28% met MCID), Health Distress +8.1 (38% MCID), Stigma +3.5 (39% MCID), and total LDQOL +2.2 (35% MCID) (all p < 0.05). Similar improvements were noted in histologic responders from 100 mg or 80 mg resmetirom groups when separated-no improvements in placebo or nonresponders. Baseline F3 histologic responders had similar/more pronounced HRQL improvements. CONCLUSIONS: Patients with MASH/NASH with fibrosis improvement or the resolution of MASH with resmetirom experienced clinically meaningful and statistically significant HRQL improvements.

Epidemiology of Metabolic Dysfunction-Associated Steatotic Liver Disease

As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does the prevalence of metabolic dysfunction associated steatotic liver disease (MASLD). Currently, 38% of all adults and 7-14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to over 55%. Although many with MASLD will not develop progressive liver disease, given the vast number of patients with MASLD, it has now become the top indication for liver transplant in the United States for those with hepatocellular carcinoma (HCC) and women. However, the most common cause of mortality among patients with MASLD remains death cardiovascular diseases. In addition to liver outcomes (cirrhosis and HCC), MASLD is associated with increased risk for the developing de-novo T2D, chronic kidney disease, sarcopenia and extrahepatic cancers. Furthermore, MASLD is associated with decreased health related quality of life, decreased work productivity, fatigue and increased healthcare resource utilization and substantial economic burden. Similar to other metabolic disease, lifestyle interventions with heathy diet and increased physical activity remain the cornerstone of managing these patients. Although a number of obesity and T2D drugs are available to treat co-morbid disease, Resmetirom is the only MASH-targeted medication that was recently approved by the Federal Drug Administration for use in the United States for those with stage 2-3 fibrosis. The following review provides an overview of MASLD epidemiology, its related risk factors and outcomes and demonstrates that without further global initiatives, MASLD may continue to increase.

Stigma in steatotic liver disease: A survey of patients from Saudi Arabia.

BACKGROUND: A recent name change of nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) to metabolic dysfunction-associated steatotic liver disease was primarily driven by potential stigma associated with the terminology. This stigma can be different between patients and healthcare providers and differ according to geographic regions of the world. Our aim was to better understand stigma and disease burden among patients with NAFLD enrolled in the global survey from Saudi Arabia (SA). METHODS: Members of the Global NASH Council created a 68-item survey about patients' experience with NAFLD, covering history of stigmatization and discrimination due to the disease, various aspects of the disease burden [(Liver Disease Burden (LDB), 35 items, 7 domains], and perception of various diagnostic terms for NAFLD. Patients whose country of residence was SA were asked to complete the survey. RESULTS: The survey was completed by 804 patients with NAFLD from SA. Of all enrolled patients, 17% ever disclosed having NAFLD/nonalcoholic steatohepatitis (NASH) to family/friends. The most commonly used term for the disease was "fatty liver" (96% used it at least sometimes, 79% frequently or always). There were 3.7% who reported experiencing stigma or discrimination (at least sometimes) due to obesity/overweight versus only 2.7% due to NAFLD. Female patients reported a history of stigmatization or discrimination more frequently than males: 5.9% versus 3.0% due to obesity ( P = 0.06) and 5.4% versus 1.8% due to NAFLD ( P = 0.01). There were 43% of patients who reported ever missing or avoiding a visit to a primary care provider due to NAFLD (48% male vs 28% female, P < 0.0001). The greatest social-emotional burden among patients with NAFLD (by LDB) was being or being identified as a person with liver disease (10% agree, 4% male vs 26% female) and feeling like they could not do anything about their liver disease (6.4% agree, 3% male vs 16% female). Regarding how patients perceived diagnostic terms, there were no substantial differences between "fatty liver disease", "NAFLD", "NASH", and "MAFLD". CONCLUSION: Stigmatization in terms of disease burden, disease-related stigma, and perception of various diagnostic terms are rarely observed in patients with NAFLD in SA. In comparison to male patients, female patients with NAFLD reported more commonly a history of stigmatization and discrimination and a significantly greater disease burden. The findings will help inform policymakers to develop programs to increase awareness and provide education about stigma related to NAFLD.

Metabolic dysfunction-associated steatotic liver disease and its link to cancer.

Metabolic-dysfunction associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a growing global health concern with significant implications for oncogenesis. This review synthesizes current evidence on the association between MASLD and cancer risk, highlighting its role as a risk factor for both intrahepatic and extrahepatic malignancies. MASLD is increasingly recognized as a major cause of hepatocellular carcinoma (HCC), with its incidence rising in parallel with the prevalence of metabolic dysfunction. Furthermore, MASLD is associated with an elevated risk of various gastrointestinal cancers, including colorectal, esophageal, stomach, and pancreatic cancers. Beyond the digestive tract, evidence suggests that MASLD may also contribute to an increased risk of other cancers such as breast, prostate, thyroid, gynecological, renal and lung cancers. Understanding the mechanisms underlying these associations and the impact of MASLD on cancer risk is crucial for developing targeted screening and prevention strategies.

Association of food insecurity with MASLD prevalence and liver-related mortality.

BACKGROUND & AIMS: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing. This study explores the association of food insecurity with MASLD prevalence and liver-related mortality (LRM) across the globe. METHODS: The study combines United Nations' country-level food security data with the MASLD data from the Global Burden of Disease study 2021. Mixed-effects linear regression models, accounting for country-level random effects, were used to assess associations of food security indicators with MASLD prevalence and LRM. The analyses were performed according to each country's socio-demographic index (SDI) status. RESULTS: In 2021, the median MASLD prevalence and liver-related mortality (MASLD-LRM) across 204 countries was 21.77% (14.14%-48.18%) and 2.92 per 100,000 (0.42-10.79) with the highest MASLD prevalence located in North Africa & Middle East (41.70%) and the lowest prevalence in high-income countries (17.31%). After adjustments for age, gender and SDI, higher MASLD prevalence was associated with increasing rates of obesity, type 2 diabetes and low physical activity (p <0.001). When analyses were performed based on SDI status, divergent patterns of MASLD prevalence were observed. In high SDI countries (socioeconomically more developed), MASLD prevalence was significantly higher in those in the top tertile of food insecurity compared to the bottom tertile (mean, 26.73% vs. 18.87%, p = 0.0001). In contrast, in low SDI countries (socioeconomically less developed), the opposite was true (19.45% vs. 24.96%, p = 0.0008). MASLD-LRM was associated with older age, obesity, and metabolic risks (p <0.001). CONCLUSIONS: MASLD prevalence and MASLD-LRM exhibit significant geographical variability, which is influenced by clinicodemographic factors, and food insecurity. Targeted public health strategies which consider the socio-economic realities of each region are essential for mitigating the global burden of MASLD. IMPACT AND IMPLICATIONS: Metabolic dysfunction-associated steatotic liver disease (MASLD) burden varies by region, influenced by food insecurity and healthcare access. In high socio-demographic index (SDI) countries, higher MASLD prevalence is linked to the consumption of low-quality, ultra-processed foods. Public health policies should focus on improving food quality, reducing unhealthy food consumption, and enhancing healthcare access. Conversely, in low SDI countries, while food insecurity can lead to outright deficiencies, the observed lower MASLD prevalence may also be partly attributable to underdiagnosis. In this context, limited healthcare access may have contributed to underestimation of the prevalence of MASLD. Therefore, country-specific policies should address both the issues related to poverty, as well as improving access to diagnostic modalities and healthcare infrastructure to ensure more accurate estimates of cases of MASLD in the specific country. Promoting physical activity is crucial in both high and low SDI countries to manage metabolic conditions associated with MASLD.

A narrative review of lifestyle management guidelines for metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) management guidelines have been published worldwide; we aimed to summarize, categorize and compare their lifestyle intervention recommendations. APPROACH RESULTS: We searched MASLD/nonalcoholic fatty liver disease (NAFLD) management guidelines published between 1 January 2013 and 31 June 2024 via databases including PubMed/MEDLINE, Cochrane, and CINAHL. In total, 35 qualifying guidelines were included in the final analysis. Guideline recommendations were categorized into five domains (i.e., 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 increase physical activity; reduce body weight by 7-10% to improve steatohepatitis and/or fibrosis; restrict caloric intake; undertake 150-300 or 75-150 minutes/week of moderate or vigorous-intensity physical activity, respectively; and decrease 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 (DHIs), 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 MASLD 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, and further exploring DHIs.

Liver Transplantation Profile Among Teenagers in the United States.

PURPOSE: Indications for liver transplantation (LT) vary across age groups. We identified predictors of outcomes for teenage LT waitlisted candidates and recipients in the United States from 2008 to 2022. METHODS: The Scientific Registry of Transplant Recipients 2008-2022 provided data (clinical, sociodemographic, indications for LT, outcomes) for all teenagers (13-19 years) waitlisted for LT in the United States. Sociodemographic and clinical characteristics, including primary listing diagnoses, were evaluated and compared by age group (13-16 vs. 17-19 years) among waitlisted teenage candidates. RESULTS: There were 2,813 teenage LT candidates listed between 2008 and 2022. The most common LT indication was acute liver disease (23.5%), followed by biliary atresia or hypoplasia (11.9%), autoimmune hepatitis (11.1%), and primary sclerosing cholangitis (9.7%). In contrast, chronic viral hepatitis, metabolic dysfunction-associated steatotic liver disease, and alcohol-related liver disease (the most common indications in adults) did not exceed 1% each; 2.8% had hepatocellular carcinoma. Excluding the two most recent years, 67.2% of candidates received a transplant; mean time to transplant was 217.0 days (standard deviation 371.6). Independent predictors of receiving a transplant were a more recent calendar year, younger age, higher model for end-stage liver disease score, and an acute liver disease diagnosis (all p < .05). Among the LT group, 3-year survival was 90%, with an improving survival trend. Higher post-transplant mortality was associated with earlier years of transplantation, older age, having Medicaid, being retransplanted, and having hepatocellular carcinoma (adjusted hazard ratios >1, all p < .05). DISCUSSION: Indications for LT among US teenagers are different from adults or younger children. There is a trend toward improved post-transplant outcomes.

The burden of metabolic dysfunction-associated steatotic liver disease and viral hepatitis in Saudi Arabia.

BACKGROUND: Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is increasing. We assessed the burden and trends of MASLD and viral hepatitis in Saudi Arabia. METHODS: Prevalence, death, and disability data due to MASLD, hepatitis C virus (HCV), and hepatitis B virus (HBV) were obtained from 2019 Global Burden of Disease (GBD) database for Saudi Arabia. Time trends were assessed by annual percent change (APC) from joinpoint regression. RESULTS: From 2012 through 2019, MASLD prevalence in children and adults increased from 28.02% ( n = 8.34 million) to 33.11% ( n = 11.83 million); APC +2.43% (95% confidence interval: 2.33% to 2.54%). HBV prevalence decreased from 1.83% ( n = 0.54 million) to 1.53% ( n = 0.55 million); APC -1.74% (-2.66% to -0.81%). HCV prevalence stabilized from 0.72% ( n = 0.21 million) to 0.73% ( n = 0.26 million): APC +0.32% (-0.13% to 0.78%). Among adults (>20 years), MASLD prevalence increased from 40.64% to 43.95% (APC = +1.15%, 1.12% to 1.18%), HBV prevalence decreased from 2.67% to 2.05% (APC = -2.96%, -3.90% to -2.01%), and HCV leveled from 0.88% to 0.86% (APC = -0.30%, -0.75% to 0.16%). MASLD liver mortality rate from liver cancer and cirrhosis increased: APC of +1.15% (0.82% to 1.48%) from 1.31 to 1.43 (per 100,000). HBV and HCV liver mortality increased at slower rates (APC = +0.78%, 0.38% to 1.19%): 2.07 to 2.20 (per 100,000) and (APC = +0.55%, 0.09% to 0.89%): 6.32 to 6.61 (per 100,000), respectively. CONCLUSIONS: MASLD burden is increasing, while HBV and HCV burden is decreasing/remaining stable. Early prevention and diagnosis health policies for MASLD are needed.

Food inequity and insecurity and MASLD: burden, challenges, and interventions.

Liver disease prevalence, severity, outcomes and hepatic risk factors (for example, unhealthy diet) are heavily affected by socioeconomic status and food insecurity. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease globally and is likely to co-occur with other liver diseases associated with food insecurity. Though weight reduction and adopting a healthy diet can reverse the course of MASLD, gaps between recommendations and practice transcend individual responsibility and preference. Broader sociocultural determinants of food choices (social nutrition) include food insecurity, community and social norms and the local environment, including commercial pressures that target people experiencing poverty, ethnic minorities and children. Food insecurity is a barrier to a healthy diet, as a low-quality diet is often less expensive than a healthy one. Consequently, food insecurity is an 'upstream' risk factor for MASLD, advanced fibrosis and greater all-cause mortality among patients with liver disease. Intervening on food insecurity at four major levels (environment, policy, community and health care) can reduce the burden of liver disease, thereby reducing social and health inequities. In this Review, we report on the current research in the field, the need for implementing proven interventions, and the role liver specialists can have.

Estimating the economic impact of comorbidities in patients with MASH and defining high-cost burden in patients with noncirrhotic MASH.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is associated with high health care costs. This US study investigated the economic burden of MASH, particularly in patients without cirrhosis, and the impact of comorbidities on health care costs. METHODS: This retrospective, observational study used data from patients diagnosed with MASH aged ≥18 years from October 2015 to March 2022 (IQVIA Ambulatory electronic medical record-US). Patients were stratified by the absence or presence of cirrhosis. Primary outcomes included baseline characteristics and annualized total health care cost after MASH diagnosis during follow-up. In addition, this study defined high costs for the MASH population and identified patient characteristics associated with increased health care costs among those without cirrhosis. RESULTS: Overall, 16,919 patients (14,885 without cirrhosis and 2034 with cirrhosis) were included in the analysis. The prevalence of comorbidities was high in both groups; annual total health care costs were higher in patients with cirrhosis. Patients with a high-cost burden (threshold defined using the United States national estimated annual health care expenditure of $13,555) had a higher prevalence of comorbidities and were prescribed more cardiovascular medications. MASH diagnosis was associated with an increase in cost, largely driven by inpatient costs. In patients without cirrhosis, an increase in cost following MASH diagnosis was associated with the presence and burden of comorbidities and cardiovascular medication utilization. CONCLUSIONS: Comorbidities, such as cardiovascular disease and type 2 diabetes, are associated with a higher cost burden and may be aggravated by MASH. Prioritization and active management may benefit patients without cirrhosis with these comorbidities. Clinical care should focus on preventing progression to cirrhosis and managing high-burden comorbidities.

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. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

Review article: Hepatic steatosis and its associations with acute and chronic liver diseases.

BACKGROUND: Hepatic steatosis is a common finding in liver histopathology and the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), whose global prevalence is rising. AIMS: To review the histopathology of hepatic steatosis and its mechanisms of development and to identify common and rare disease associations. METHODS: We reviewed literature on the basic science of lipid droplet (LD) biology and clinical research on acute and chronic liver diseases associated with hepatic steatosis using the PubMed database. RESULTS: A variety of genetic and environmental factors contribute to the development of chronic hepatic steatosis or steatotic liver disease, which typically appears macrovesicular. Microvesicular steatosis is associated with acute mitochondrial dysfunction and liver failure. Fat metabolic processes in hepatocytes whose dysregulation leads to the development of steatosis include secretion of lipoprotein particles, uptake of remnant lipoprotein particles or free fatty acids from blood, de novo lipogenesis, oxidation of fatty acids, lipolysis and lipophagy. Hepatic insulin resistance is a key feature of MASLD. Seipin is a polyfunctional protein that facilitates LD biogenesis. Assembly of hepatitis C virus takes place on LD surfaces. LDs make important, functional contact with the endoplasmic reticulum and other organelles. CONCLUSIONS: Diverse liver pathologies are associated with hepatic steatosis, with MASLD being the most important contributor. The biogenesis and dynamics of LDs in hepatocytes are complex and warrant further investigation. Organellar interfaces permit co-regulation of lipid metabolism to match generation of potentially toxic lipid species with their LD depot storage.