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 survey for hepatologists and gastroenterologists, the second for non-specialists (e.g. endocrinologists, primary care providers (PCPs), 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 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 for 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.

Health-Related quality of life (HRQL) assessments in a 52-Week, Double-Blind, randomized, Placebo-Controlled phase 3 study of resmetirom (MGL-3196) in patients with metabolic dysfunction associated steatohepatitis (MASH) and fibrosis.

BACKGROUND/AIMS: Resmetirom, liver directed thyroid-hormone receptor-ß agonist, received approval for MASH treatment. We assessed HRQL in MASH patients treated with resmetirom. METHODS: Non-cirrhotic MASH/NASH patients with confirmed/suspected fibrosis were enrolled in a 54-month double-blind randomized placebo-controlled Phase 3 clinical trial with serial biopsy assessments (MAESTRO-NASH, NCT03900429) at baseline and Week 52. 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. RESULTS: Included were 966 ITT patients: 323 received resmetirom 100 mg, 322 resmetirom 80 mg, 321 placebo. By weeks 24 and 52, patients receiving 80 or 100 mg resmetirom experienced HRQL improvement 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 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 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: MASH/NASH patients with fibrosis improvement or resolution of MASH with resmetirom experienced clinically meaningful and statistically significant HRQL improvements.

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.

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.

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.

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.

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.

Association of Food Insecurity with the Prevalence and Liver-related Mortality of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

BACKGROUND: The burden of MASLD is growing across the globe. This study explores 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 Global Burden of Disease-2021. Mixed-effects linear regression (MELR) 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 Socioeconomic Development Index (SDI) status. RESULTS: In 2021, the median prevalence and LRM of MASLD 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 (T2D) 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 as 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: And Relevance: MASLD prevalence and LRM exhibit significant geographical variability across the globe which can be influenced by clinic-demographic, and food insecurity. Targeted public health strategies which considers socio-economic realities of each region are essential for mitigating the global burden of MASLD.

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.

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.

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.

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.

Envisioning how to advance the MASH field.

Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has led to, among others, the approval of the first drug specific for metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis). Despite substantial progress, MASLD is still a leading cause of advanced chronic liver disease, including primary liver cancer. This Perspective contextualizes the nomenclature change from nonalcoholic fatty liver disease to MASLD and proposes important considerations to accelerate further progress in the field, optimize patient-centric multidisciplinary care pathways, advance pharmacological, behavioural and diagnostic research, and address health disparities. Key regulatory and other steps necessary to optimize the approval and access to upcoming additional pharmacological therapeutic agents for MASH are also outlined. We conclude by calling for increased education and awareness, enhanced health system preparedness, and concerted action by policy-makers to further the public health and policy agenda to achieve at least parity with other non-communicable diseases and to aid in growing the community of practice to reduce the human and economic burden and end the public health threat of MASLD and MASH by 2030.

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.

Validation of a Primary Biliary Cholangitis-Specific Version of Chronic Liver Disease Questionnaire: CLDQ-PBC.

INTRODUCTION: Primary biliary cholangitis (PBC) is a chronic liver disease, leading to cirrhosis and impairment of patient-reported outcomes. We aimed to develop a PBC-specific version of the Chronic Liver Disease Questionnaire (CLDQ) instrument to assess health-related quality of life of patients with PBC. METHODS: From our Liver Database, we included patients with PBC who had CLDQ, clinicolaboratory data, and completed Short Form-36 and The Functional Assessment of Chronic Illness Therapy-Fatigue. The 29 items of CLDQ were subjected to item reduction, exploratory factor analysis, and fed into a standard instrument validation pipeline. RESULTS: Data were available for 108 patients with PBC: 57 ± 11 years, 7% male, 58% cirrhosis, and 24% decompensated cirrhosis (Child B and C). Of 29 CLDQ items, none met the exclusion criteria. Exploratory factor analysis (95% of variance) returned 7 factors. Based on evaluation of factor loadings and face validity, those factors yielded 7 domains (Diet, Emotion, Fatigue, Itch, Symptoms, Sleep, and Worry). Good to excellent internal consistency (Cronbach's α 0.85-0.93) was observed for 5/7 domains. For the remaining 2 domains (Diet and Itch), additional items obtained from patients, experts, and review of the literature were included. For 5 domains, known-group validity tests discriminated between patients with PBC with and without cirrhosis, advanced cirrhosis, and depression ( P < 0.05 for 3-5 domains). The CLDQ-PBC domains were correlated with relevant domains of Short Form-36, CLDQ-PBC Fatigue correlated with Fatigue Scale of Functional Assessment of Chronic Illness Therapy-Fatigue (rho = +0.85), and CLDQ-PBC Worry domain negatively correlated with alkaline phosphatase (rho = -0.38, P = 0.0082). DISCUSSION: The CLDQ-PBC has been developed based on the original CLDQ. The new instrument has evidence for internal consistency and validity and is being fully validated using an external cohort.