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Patient-reported outcomes (PROs), such as health-related quality of life (HRQL), are important outcome measures for patients with chronic liver diseases (CLDs). Presence of cirrhosis and advanced liver disease have been associated with worsened HRQL and fatigue. On the other hand, some patients with earlier stages of CLD also experience fatigue, causing PRO impairment. Treatment for some CLDs may improve HRQL and, sometimes, levels of fatigue. We aimed to provide an in-depth expert review of concepts related to fatigue and HRQL in patients with primary biliary cholangitis, hepatitis C virus and MASLD (metabolic dysfunction-associated steatotic liver disease). A panel of experts in fatigue and CLD reviewed and discussed the literature and collaborated to provide this expert review of fatigue in CLD. Herein, we review and report on the complexity of fatigue, highlighting that it is comprised of peripheral (neuromuscular failure, often in conjunction with submaximal cardiorespiratory function) and central (central nervous system dysfunction) causes. Fatigue and HRQL are measured using validated self-report instruments. Additionally, fatigue can be measured through objective tests (e.g. grip strength). Fatigue has deleterious effects on HRQL and one's ability to be physically active and socially engaged but does not always correlate with CLD severity. Treatments for hepatitis C virus and MASLD can improve levels of fatigue and HRQL, but current treatments for primary biliary cholangitis do not seem to affect levels of fatigue. We conclude that obtaining PRO data, including on HRQL and fatigue, is essential for determining the comprehensive burden of CLD and its potential treatments., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers., Methods: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey., Results: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%)., Conclusions: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties., Impact and Implications: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma., Competing Interests: Conflict of interest ZMY: research funding or consultation fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cymabay, GlaxoSmithKline, Intercept, Novo Nordisk, Siemens, Madrigal, Merck; VWSW: served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, Visirna, speaker for Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Unilab, received a research grant from Gilead Sciences, co-founder of Illuminatio Medical Technology Limited; AMA: grant funding from NIH, Novo Nordisk, Target Pharma, consulting/advisory board for Novo Nordisk; JMS: consultant for Astra Zeneca, Apollo Endosurgery, Bayer, Boehringer Ingelheim, BMS, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers, receives research funding from Gilead Sciences, Boehringer Ingelheim, Siemens Healthcare GmbH, has stock options of AGED diagnostics, Hepta Bio, received speaker honorarium from Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, Madrigal Pharmaceuticals, Histoindex, MedPublico GmbH; CWS: speaker bureau fees from Gilead Sciences, Abbott; RL: receives funding support from NCATS, NIDDK, NHLBI, serves as a consultant to Aardvark Therapeutics, Altimmune, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, Terns Pharmaceuticals, co-founder of LipoNexus Inc; PC: received research grants by MSD and Intercept. Other coauthors report no conflicts of interest related to this study. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Hepatocellular carcinoma (HCC) is frequently a lethal disease and one of the few malignancies that is still increasing in incidence around the world. Better animal models are highly desired to investigate the molecular basis of HCC and to develop novel therapeutic strategies. Alpha-fetoprotein (Afp) gene is expressed in fetal liver, silenced soon after birth, and highly re-expressed in hepatocellular carcinomas (HCC). We aimed to take advantage of the dramatic re-expression of the Afp gene in HCC to develop a hepatocarcinogenesis reporter (HCR) mouse model for dual-modality, longitudinal in vivo imaging of liver tumor development, and progression., Methods: Knock in mice were established by placing a thymidinekinase (tk)-luciferase (luc) reporter gene cassette under the transcriptional control of the endogenous Afp promoter. DEN, a liver carcinogen, was used to induce liver tumors, which was monitored by both luc-based bioluminescent (BL) and tk-based positron emission tomography (PET) imaging., Results: The expression profile of luc was identical to that of the endogenous Afp gene during development. As early as 2 months after the exposure to DEN, BLI revealed multifocal signals in the liver, long before the appearance of histologically apparent neoplastic lesions. By 6 months, BL and PET dual imaging showed strong signals in malignant HCC. By serendipity, a strong BL signal was also detected in adult testes, a previously unknown site of Afp expression., Conclusions: The HCR model enables longitudinal monitoring of liver tumor development and progression, providing a powerful tool in developing chemoprevention and therapeutic strategies for HCC., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)