Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin–like receptor CLEC7A on Kupffer cells and possibly other bone marrow–derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non–alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease.

One of the most important statistical analyses when designing animal and human studies is the calculation of the required sample size. In this review, we define central terms in the context of sample size determination, including mean, standard deviation, statistical hypothesis testing, type I/II error, power, direction of effect, effect size, expected attrition, corrected sample size, and allocation ratio. We also provide practical examples of sample size calculations for animal and human studies based on pilot studies, larger studies similar to the proposed study—or if no previous studies are available—estimated magnitudes of the effect size per Cohen and Sawilowsky.

With its increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a major global public health concern over the past few decades. Growing evidence has proposed the microbiota-derived metabolites short-chain fatty acids (SCFAs) as a potential factor in the pathophysiology of MASLD and related metabolic conditions, such as obesity and type 2 diabetes mellitus (T2DM). By influencing key pathways involved in energy homeostasis, insulin sensitivity, and inflammation, SCFAs play an important role in gut microbiota composition, intestinal barrier function, immune modulation, and direct metabolic signaling. Furthermore, recent animal and human studies on therapeutic strategies targeting SCFAs demonstrate their potential for treating these metabolic disorders.

Background and Aims: NAFLD in adolescents is an increasing health crisis worldwide, but its exact global, continental, and national prevalence, its relationship with other metabolic conditions, and the human development index (HDI) globally are not known. Approach and Results: We analyzed data from the Global Burden of Disease Study 2019 to compare global, continental, and national prevalence rates of adolescent NAFLD and associations with other metabolic conditions and HDI. The global NAFLD prevalence in adolescents increased from 3.73% in 1990 to 4.71% in 2019 (a relative increase of 26.27%). The prevalence for the male and female populations was 5.84% and 3.52% in 2019, respectively. The Oceanian and North American continents had the highest adolescent NAFLD prevalence (median: 6.54% and 5.64%, respectively), whereas Europe had the lowest prevalence (median: 3.98%). South America and North America had the highest relative increase in adolescent NAFLD prevalence from 1990 to 2019 (median: 39.25% and 36.87%, respectively). High body mass index and type 2 diabetes mellitus increased significantly in adolescents worldwide. However, only high body mass index and not type 2 diabetes mellitus correlated with NAFLD prevalence in adolescents globally. Countries with a higher HDI had larger increases in adolescent NAFLD prevalence from 1990 to 2019 although countries with the highest HDI (HDI: > 0.9) had the lowest NAFLD prevalence in 2019. Conclusions: NAFLD in adolescents is an increasing health problem on all continents. Improving environmental factors, including lifestyle but also healthcare policies, can help to prevent NAFLD from developing in children and adolescents and help to improve outcomes in children and adolescents with NAFLD.

Importance: Pediatric obesity is associated with complications such as metabolic dysfunction–associated steatotic liver disease (MASLD), type 2 diabetes, dyslipidemia, and hypertension. However, data on the prevalence of extremely severe obesity in childhood and adolescence and its associated complications are lacking.Objective: To assess trends in pediatric obesity over time and to investigate the association between obesity degree and comorbidities.Design, Setting, and Participants: This cross-sectional study included data from nationally representative samples of pediatric participants aged 2 to 18 years from the National Health and Nutrition Examination Survey (NHANES) from 2008 through 2023. NHANES is a US cross-sectional survey assessing health and nutrition through questionnaires, physical examinations, and laboratory tests.Exposure: Pediatric obesity, classified as follows: traditional classes 1 to 3 obesity (body mass index [BMI] ≥95th percentile to <160% of the 95th percentile) and extremely severe obesity, comprising class 4 (BMI ≥160% to <180% of 95th percentile) and class 5 (BMI ≥180% of 95th percentile) obesity.Main Outcomes and Measures: The main outcomes were national trends in prevalence of obesity classes in childhood and adolescence, stratified by gender, age, and ethnicity and race, and odds of conditions of metabolic dysfunction in each obesity group.Results: The cohort included 25 847 participants (51% male) with a median age of 10.0 (IQR, 6.00-15.0) years. From 2008 to 2023, the prevalence of pediatric obesity increased, with the highest relative increase of 253.1% observed for extremely severe obesity from 0.32% (95% CI, 0.17%-0.59%) in 2008 to 1.13% (95% CI, 0.78%-1.65%) in 2023. From 2020 to 2023, extremely severe obesity was particularly prevalent among adolescents aged 16 to 18 years (1.99%; 95% CI, 1.31%-2.99%) and non-Hispanic Black participants (2.04%; 95% CI, 1.45%-2.86%). Compared with milder forms of obesity, extremely severe obesity was associated with higher odds of metabolic complications, including MASLD (odds ratio [OR], 6.74; 95% CI, 3.30-15.75), prediabetes or diabetes (OR, 4.94; 95% CI, 3.41-7.14), severe insulin resistance (OR, 8.05; 95% CI, 3.70-17.02), and metabolic syndrome (OR, 1.99; 95% CI, 1.45-2.73).Conclusions and Relevance: In this nationally representative cross-sectional study of US children and adolescents, prevalence of extremely severe obesity significantly increased over time, particularly among older adolescents and non-Hispanic Black participants. Extremely severe obesity was associated with severe metabolic and cardiovascular complications, including MASLD, prediabetes or diabetes, severe insulin resistance, and metabolic syndrome. These findings emphasize the urgent need for public health interventions and policies to address pediatric obesity broadly.