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Background The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. Results We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, and a central role in a pro-fibrotic TGFβ signaling cell–cell communications network. Integrated analysis and comparisons with healthy controls reveal extensive changes in the cellular composition and expression states in COVID-19 liver, providing the underpinning of hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis characteristic of COVID-19 cholangiopathy. We also observe Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition is dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Conclusions Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

Cirrhosis, a rising cause of death in the United States, has an extended preclinical phase characterized by progressive liver fibrosis. Despite the developments in noninvasive fibrosis measurement, there is no recommended screening, in part due to an incomplete understanding of the disease epidemiology on a national scale. Herein, we aim to define the prevalence of liver fibrosis and compare strategies to identify the at‐risk population. We analyzed 4,510 US adults with complete liver stiffness measurement (LSM) by vibration‐controlled transient elastography (VCTE) in the 2017‐2018 National Health and Nutrition Examination Survey to estimate the disease burden of increased liver stiffness. An estimated 11.6 million (95% confidence interval [C.I.], 8.1‐15.0 million) US adults had LSM ≥9.5 kPa, indicating advanced fibrosis and representing 1 in every 18 adults. Among them, 7.1 million (95% CI, 5.0‐9.1 million) had LSM ≥12.5 kPa, which is concerning for cirrhosis. LSM ≥9.5 kPa is associated with male sex (S), history of other liver diseases (O), diabetes (D), advanced age (A), and an elevated BMI (B). A simple SODA‐2B score had a sensitivity of 96.4% in identifying individuals at risk for advanced cirrhosis (LSM ≥9.5 kPa) and a negative predictive value of 99.3% in stratifying more than half of the adult population. When the liver function test (LFT) is available, the inclusion of abnormal LFT and elevated fibrosis‐4 index can further increase screening efficiency. Conclusion: Elevated liver stiffness is prevalent among US adults. A SODA‐2B score can risk stratify adults for VCTE‐based fibrosis screening.

Diabetic kidney disease (DKD) is the major contributor to the mortality and the financial burden of diabetes, accounting for approximately 50% of the cases of end‐stage renal disease (ESRD) in the developed world. Several studies have already demonstrated that achieving blood pressure targets in DKD with agents blocking the renin‐angiotensin system confer superior renoprotection when compared to other agents. However, the effects on renal outcomes of antihyperglycaemic agents in these patients have not been reported or studied broadly until recent years. The intent of this article is to review the available data on safety, efficacy, impact on renal outcomes and pathophysiology implications of the most utilized antihyperglycaemic agents in DKD/ESRD. We summarized the current data and recommendations on the safety and efficacy of antihyperglycaemic agents in patients with diabetic kidney disease.

COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure 1 – 4 , but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63 + intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments. Single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe COVID-19 infection.

Background & AimLiver fibrosis is associated with poor patient-reported outcomes (PROs), but the impact of steatosis is unknown. We aimed to evaluate the impact of steatosis on PROs independent of liver fibrosis.MethodsWe evaluated the impact of steatosis, measured by Controlled-Attenuation Parameter (CAP) on transient elastography, and PROs using the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We used univariate and multivariate logistic and ordinal regression to evaluate categorical CAP score with PROs measuring physical disability, general health and depression.ResultsOf 4,509 participants included, 38% had severe steatosis (> 280 dB/m). Those with severe steatosis were older and more likely to be male (56% vs. 43% and 51%). On univariate analysis, severe steatosis was associated with more difficulty walking (P = 0.01), dressing (P = 0.005), lifting objects (P = 0.02), bending (P < 0.001), and moving large objects (P = 0.0006). After multivariate adjustment, severe steatosis remained associated with difficulty lifting objects (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.2–2.4, P = 0.01) and difficulty bending (OR: 1.8, 95% CI: 1.2–2.7, P = 0.006). Severe steatosis increased risk of having any of the disabilities (OR: 1.7, 95% CI: 1.2–2.4, P = 0.008) and had higher ordinal disability index (OR: 1.6, 95% CI: 1.2–2.2, P = 0.007). Lastly, severe steatosis was also associated with worse self-perceived health status (OR: 1.5, 95% CI: 1.2–1.9, P = 0.002), while general health compared to one year ago and depression trended toward significance.ConclusionPatients with severe steatosis are at increased risk of physical disability and have worse self-perceived health status independent of liver fibrosis.

Chronic liver disease (CLD) is a major healthcare burden for the United States, responsible for 60,000 deaths annually and recently surpassing heart failure hospitalization rates. We analyzed 4,510 adults sampled by the National Health and Nutrition Examination Survey (NHANES) in the cycle of 2017-2018 who underwent non- invasive vibration-controlled transient elastography (VCTE). Participants are enrolled using a stratified multistage probability with an oversampling design that allows a weighted and simplified representation of the civilian US population.In the first paper, we intended to examine the national estimated prevalence of increased liver stiffness (LSM) measured by VCTE among these participants to characterize the at-risk population. Once the proportion and phenotype were identified, we constructed a screening score based on the variables associated with increased liver stiffness and advanced cirrhosis. The score was validated by calculating C- statistics and compared to the recommended screening FIB-4 score.VCTE data from the same cohort provided controlled attenuation parameter (CAP), which measures hepatic steatosis.Alcohol-associated liver disease (ALD) is responsible for rising rates of cirrhosis and liver-related mortality in the US. It is also one of the most common causes of fatty liver disease (FLD), which is the major contributor of CLD. Considering the lack of evidence on the mechanism and the quantity of alcohol that contributes to fatty liver disease progression, we performed multiple regression models in the second paper using dietary recall to identify the associations between the multiple consumption dimensions and the type of alcohol consumed with hepatic steatosis.

Recent investigations have shown that different conditions such as diet, the overuse of antibiotics or the colonization of pathogenic microorganisms can alter the population status of the intestinal microbiota. This modification can produce a change from homeostasis to a condition known as imbalance or dysbiosis; however, the role-played by dysbiosis and the development of inflammatory bowel diseases (IBD) has been poorly understood. It was actually not until a few years ago that studies started to develop regarding the role that dendritic cells (DC) of intestinal mucosa play in the sensing of the gut microbiota population. The latest studies have focused on describing the DC modulation, specifically on tolerance response involving T regulatory cells or on the inflammatory response involving reactive oxygen species and tissue damage. Furthermore, the latest studies have also focused on the protective and restorative effect of the population of the gut microbiota given by probiotic therapy, targeting IBD and other intestinal pathologies. In the present work, the authors propose and summarize a recently studied complex axis of interaction between the population of the gut microbiota, the sensing of the DC and its modulation towards tolerance and inflammation, the development of IBD and the protective and restorative effect of probiotics on other intestinal pathologies.

Introduction: Colonoscopy is one of the most effective methods to prevent colorectal cancer. Social media has emerged as a source of medical information for patients, of which YouTube, a video sharing website, is one of the most popular video informative sources. Therefore, we aimed to assess the educational quality of colonoscopy videos available on YouTube. Methods: We performed a YouTube search using the keyword \"colonoscopy\" from 9th to 18th September 2017. The initial search yielded 429 videos out of which 255 were included in the analysis as summarized in Fig 1. We created a scoring system, Colonoscopy Data Quality Score (C-DQS), based on a colonoscopy education video available on ASGE website to rate the quality of the videos. Negative points were assigned for misleading information. We also scored each video by a previously published method called the global quality score (GQS) for comparison. Six blinded reviewers viewed the videos and scored each video independently. The two-tailed analysis was performed for video characteristics. ANOVAs were performed to compare scores by video type. ICC, a quantitative measurement, was used to assess the similarity of the C-DQS score of videos among reviewers; a score between 0.75 and 1.00 is considered excellent. Results: A total of 255 videos were analyzed. 45.2% of presenters were male, and 62.5% were white. The most common type of video source and video content was professional societies (44.3%) and patient education (65.9%), respectively. Videos from media (5.26), health-care providers (5.20), and professional societies (5.10) had higher mean C-DQS, while videos from alternative medicine providers (4.98), companies (4.93), and patient and/or patient parents (4.68) had lower mean C-DQS (Table 1). Alternative medicine videos included the misleading information such as \"Colonoscopy is actually useless\" and \"Colonoscopy may actually increase the risk of colon cancer.\" Our scoring system (C-DQS) correlates with the previously published GQS (Fig 2). There was a high degree of agreement among reviewers for the videos from all sources (ICC= 0.934; P<0.001). Conclusion: In general, YouTube videos are a poor source of healthcare related information on colonoscopy. Out of all sources, News Media is a better source of quality information for patient education on colonoscopy compared to other sources. The medical community may need to engage actively in enriching the quality of educational material available on YouTube.

Introduction: The Hispanic population in the US faces a higher risk of nonalcoholic fatty liver disease (NAFLD). Multiple factors influence this risk, including genetics, environmental factors, and socioeconomic statuses. Inadequate access to nutritious foods, or food insecurity, is prevalent among Hispanic individuals and poses a metabolic risk for both the onset and development of NAFLD. Materials and Methods: We utilized the National Health and Nutrition Examination Survey (NHANES) 2017–2020 pre-pandemic data to analyze the association between Hispanic ethnicity, hepatic steatosis, fibrosis, and food insecurity. Vibration-controlled transient elastography (VCTE) was employed to assess liver stiffness (LSM) and controlled attenuation parameter (CAP) scores to determine fibrosis and steatosis, respectively. Linear and ordinal logistic regression models were applied to their continuous, log-transformed, and categorical forms, adjusting for demographics, metabolic comorbidities, and socioeconomic factors. Models were subsequently stratified based on food security statuses. Results: A total of 7396 Hispanic participants were included in the study. Under multivariable analysis, Hispanic individuals had higher CAP scores (Beta-coefficient: 10.2 dB/m, 95% CI: 6.1–14.4 dB/m, p = 0.001)) vs. non-Hispanic individuals, without statistically significant differences in fibrosis. Food-insecure participants exhibited higher CAP scores than their food-secure counterparts. After stratification, a stronger association between Hispanic ethnicity and CAP scores was evident in the food-insecure group (Beta-coefficient: 11.8 dB/m, 95% CI: 4.4–19.3 dB/m, p = 0.003). Discussion: This study demonstrates the heightened risk of hepatic steatosis among individuals with Hispanic ancestry in the US. The risk is exacerbated by food insecurity, particularly for Hispanic individuals. The contribution is linked to the dietary habits in this population that lead to metabolic risk factors associated with hepatic steatosis. Considering the rising prevalence of NAFLD and food insecurity, interventions focusing on nutritional support and healthcare access among this population could mitigate these burdens.