Impact of Liver Transplantation on Adipose Tissue Compartments and Its Association With Metabolic Sequela.

BACKGROUND: Loss of skeletal muscle can be accompanied by an increase in adipose tissue leading to sarcopenic obesity. There are limited data on how liver transplantation (LT) might impact adipose tissue compartments, particularly among patients with metabolically active disease, such as nonalcoholic steatohepatitis (NASH) and subsequent metabolic sequela. METHODS: Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured using cross-sectional imaging performed in 190 patients pre-LT, 6 mo post-LT and 12 mo post-LT. Changes in adipose tissue and their impact on metabolic diseases were determined in patients transplanted for NASH versus non-NASH. RESULTS: Skeletal muscle, VAT, and SAT were similar in patients with NASH and non-NASH pre-LT despite a higher burden of metabolic diseases in patients with NASH. Following LT, no significant differences between skeletal muscle and SAT were observed in the entire cohort and among patients with NASH (versus non-NASH). LT recipients with the highest muscle mass pre-LT were at the greatest risk for muscle loss post-LT. A time-dependent increase in VAT was noted post-LT, which was more robust among patients with a history of NASH cirrhosis. In adjusted multivariate analysis, NASH versus non-NASH was a strong predictor of post-LT increase in VAT (ß-coefficient 3.00, P = 0.04). Pre-LT VAT was an independent predictor of post-LT serum triglycerides (ß-coefficient 5.49 ± 2.78, P = 0.05) and low-density lipoprotein cholesterol (ß-coefficient 1.80 ± 0.75, P = 0.02). A trend between pre-LT VAT and diabetes was noted but did not reach statistical significance. CONCLUSIONS: VAT but not SAT increases rapidly after LT, especially among patients transplanted for NASH cirrhosis and predicts future metabolic burden.

Donor Diabetes and Steatosis Affects Recipient Survival Following Liver Transplantation Based on Etiology of Liver Cirrhosis.

BACKGROUND: Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT. METHODS: This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis. RESULTS: Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P < 0.001). Importantly, donor diabetes was associated with increased all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence interval [CI], 1.07-1.19; P < 0.001) and graft failure (HR: 1.16; 95% CI, 1.11-1.22; P < 0.001). Receiving donor organ with diabetes reduced graft survival in patients who received LT for nonalcoholic steatohepatitis cirrhosis (HR: 1.26; 95% CI, 1.13-1.41; P < 0.001) but not other etiologies of cirrhosis. CONCLUSIONS: Donor diabetes was associated with worse outcomes post-LT, particularly in patients receiving LT for nonalcoholic steatohepatitis cirrhosis. Future studies are needed to better understand the mechanism underlying this association to develop better risk stratification and clinical practice to improve the outcomes of the transplanted patients.

Impact of Pretransplant Diabetes on Outcomes After Liver Transplantation: An Updated Meta-analysis With Systematic Review.

BACKGROUND: Preliver transplant diabetes mellitus (pre-LT DM) is a common comorbidity in LT recipients associated with poorer post-transplant survival. However, its relationship with other important outcomes, including cardiovascular and renal outcomes, remains unclear. This meta-analysis aims to provide an updated analysis of the impact of pre-LT DM on key post-LT outcomes. METHODS: A search was conducted in Medline and Embase databases for articles comparing the post-transplant outcomes between patients with and without pre-LT DM. Pairwise analysis using random effects with hazard ratios (HRs) was used to assess the longitudinal post-LT impacts of pre-LT DM. In the absence of HR, pooled odds ratios analysis was conducted for secondary outcomes. RESULTS: Forty-two studies involving 77,615 LT recipients were included in this analysis. The pooled prevalence of pre-LT DM amongst LT recipients was 24.79%. Pre-LT DM was associated with significantly lower overall survival (HR, 0.65; 95% confidence interval, 0.52-0.81; P<0.01) and significantly increased cardiovascular disease-related mortality (HR, 1.78; 95% confidence interval, 1.11-2.85; P=0.03). Meta-regression of other patient characteristics identified Asian ethnicity and hypertension to be significant predictors of worse overall survival, whereas African-American ethnicity was associated with significantly improved overall survival in patients with pre-LT DM. Further analysis of secondary outcomes revealed pre-LT DM to be a significant predictor of post-LT cardiovascular events and end-stage renal disease. CONCLUSIONS: The present study illustrates the impact of pre-LT DM on post-LT survival, and cardiovascular and renal outcomes and provides a sound basis for revision of preoperative management of pre-LT DM.

A Rare Case of Acquired Factor VIII Deficiency in an Elderly Male With a History of Rheumatoid Arthritis.

Acquired hemophilia A (AHA) or factor VIII (FVIII) deficiency is caused by autoantibodies targeting FVIII in the blood coagulation pathway; it is a rare condition making it challenging to diagnose. A timely diagnosis is crucial, without which there is a risk of catastrophic bleeding. We report a case of a patient with a history of duodenal arteriovenous malformations, previously on apixaban, who presented with four days of melena. On admission he was found to have a hemoglobin of 5.7 and elevated partial thromboplastin time (PTT), promoting further workup showing FVIII levels of <1%, with a mixing study that failed to correct suggesting the presence of inhibitors against FVIII. Other characteristics of this patient's cases included controlled rheumatoid arthritis without detectable rheumatoid factor or increased erythrocyte sedimentation rate (ESR). The patient was initially treated with prednisone and intravenous immunoglobulins, but an insufficient response prompted the initiation of recombinant factor VII, rituximab, and cyclophosphamide during hospitalization.

Macrophage Polarization Status Impacts Nanoceria Cellular Distribution but Not Its Biotransformation or Ferritin Effects.

The innate immune system is the first line of defense against external threats through the initiation and regulation of inflammation. Macrophage differentiation into functional phenotypes influences the fate of nanomaterials taken up by these immune cells. High-resolution electron microscopy was used to investigate the uptake, distribution, and biotransformation of nanoceria in human and murine M1 and M2 macrophages in unprecedented detail. We found that M1 and M2 macrophages internalize nanoceria differently. M1-type macrophages predominantly sequester nanoceria near the plasma membrane, whereas nanoceria are more uniformly distributed throughout M2 macrophage cytoplasm. In contrast, both macrophage phenotypes show identical nanoceria biotransformation to cerium phosphate nanoneedles and simultaneous nanoceria with ferritin co-precipitation within the cells. Ferritin biomineralization is a direct response to nanoparticle uptake inside both macrophage phenotypes. We also found that the same ferritin biomineralization mechanism occurs after the uptake of Ce-ions into polarized macrophages and into unpolarized human monocytes and murine RAW 264.7 cells. These findings emphasize the need for evaluating ferritin biomineralization in studies that involve the internalization of nano objects, ranging from particles to viruses to biomolecules, to gain greater mechanistic insights into the overall immune responses to nano objects.

Hepatic, Extra-hepatic Outcomes and Causes of Mortality in NAFLD - An Umbrella Overview of Systematic Review of Meta-Analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease globally. While the prevalence, impact, and causes of mortality have been described in various meta-analyses, a systematic all-encompassing umbrella review has yet to be conducted to consolidate the evidence on outcomes associated with NAFLD. Methods: Search was conducted on Medline and Embase for meta-analysis investigating associated complications and causes of mortality in NAFLD patients. Summary estimates were presented with original units, sample size, and I2 for heterogeneity. The Assessment of Multiple Systematic Reviews 2 was employed for article selection. Results: 25 meta-analyses were included in the present review. NAFLD increased the risks of systemic complications, including cardiovascular diseases, systemic malignancies, diabetes, and chronic kidney disease. Regarding hepatic outcomes, the incidence of hepatocellular carcinoma in NAFLD was 2.39 per 100 person years (CI: 1.40 to 4.08). Individuals with NAFLD were also found to have an increased likelihood of cholangiocarcinoma (OR: 1.88, CI: 1.25 to 2.83) and gallstone disease (OR: 1.55, CI: 1.31 to 1.82) compared to individuals without NAFLD. NAFLD was associated with a higher risk of fatal and non-fatal CVD events (HR: 1.45, CI: 1.31 to 1.61) compared to individuals without NAFLD. Coronary heart disease and subclinical and clinical coronary heart disease were also significantly elevated in NAFLD individuals compared to individuals without NAFLD. Additionally, NAFLD was associated with an increased risk of all-cause mortality (HR: 1.34, CI: 1.17 to 1.54) and cardiovascular (HR: 1.30, CI: 1.08 to 1.56) but not cancer-related mortality. Conclusion: The study summarizes high-level evidence from published meta-analyses to provide a much-needed update on the outcomes in patients with NAFLD. The significant systemic burden associated with NAFLD and impending fatty liver epidemic requires prompt action from multidisciplinary providers, policy providers, and stakeholders to reduce the burden of NAFLD.

Natural history of NASH cirrhosis in liver transplant waitlist registrants.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) cirrhosis is rapidly growing as an indication for liver transplant(ation) (LT). However, the natural history of NASH cirrhosis among LT waitlist registrants has not been established. The present study aimed to define the natural history of NASH cirrhosis using the Scientific Registry of Transplant Recipients database. METHODS: The study cohort comprised patients registered on the LT waitlist between 1/1/2016 to 12/31/2021. The primary outcomes included probability of LT and waitlist mortality, comparing NASH (n = 8,120) vs. non-NASH (n = 21,409) cirrhosis. RESULTS: Patients with NASH cirrhosis were listed with lower model for end-stage liver disease (MELD) scores despite bearing a greater burden of portal hypertension, especially at lower MELD scores. The overall transplant probability in LT waitlist registrants with NASH [vs. non-NASH] cirrhosis was significantly lower at 90 days (HR 0.873, p <0.001) and 1 year (HR 0.867, p <0.001); this was even more pronounced in patients with MELD scores >30 (HR 0.705 at 90 days and HR 0.672 at 1 year, p <0.001 for both). Serum creatinine was the key contributor to MELD score increases leading to LT among LT waitlist registrants with NASH cirrhosis, while bilirubin was in patients with non-NASH cirrhosis. Finally, waitlist mortality at 90 days (HR 1.15, p <0.001) and 1 year (1.25, p <0.001) was significantly higher in patients with NASH cirrhosis compared to those with non-NASH cirrhosis. These differences were more pronounced in patients with lower MELD scores at the time of LT waitlist registration. CONCLUSIONS: LT waitlist registrants with NASH cirrhosis are less likely to receive a transplant compared to patients with non-NASH cirrhosis. Serum creatinine was the major contributor to MELD score increases leading to LT in patients with NASH cirrhosis. IMPACT AND IMPLICATIONS: This study provides important insights into the distinct natural history of non-alcoholic steatohepatitis (NASH) cirrhosis among liver transplant (LT) waitlist registrants, revealing that patients with NASH cirrhosis face lower odds of transplantation and higher waitlist mortality than those with non-NASH cirrhosis. Our study underscores the significance of serum creatinine as a crucial contributor to model for end-stage liver disease (MELD) score in patients with NASH cirrhosis. These findings have substantial implications, emphasizing the need for ongoing evaluation and refinement of the MELD score to more accurately capture mortality risk in patients with NASH cirrhosis on the LT waitlist. Moreover, the study highlights the importance of further research investigating the impact of the implementation of MELD 3.0 across the US on the natural history of NASH cirrhosis.

Ethnic disparities in waitlist outcomes of patients with nonalcoholic steatohepatitis listed for liver transplantation in the US.

NASH is the fastest-growing cause of liver cirrhosis and is the leading indication for liver transplantation (LT). However, significant racial and ethnic disparities in waitlist outcomes and LT allocation may unfairly disadvantage minorities. Our aim was to characterize racial and ethnic disparities in waitlist mortality and transplantation probability among patients with NASH. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT candidates from January 1, 2000 to December 31, 2021. Outcomes analysis was performed using competing risk analysis with the Fine and Gray model. The multivariable adjustment was conducted, and mixed-effect regression was used to compare the model for end-stage liver disease scores at listing and removal. Of 18,562 patients with NASH cirrhosis, there were 14,834 non-Hispanic Whites, 349 African Americans, 2798 Hispanics, 312 Asians, and 269 of other races/ethnicities; African American (effect size: 2.307, 95% CI: 1.561-3.053, and p < 0.001) and Hispanic (effect size: 0.332, 95% CI: 0.028-0.637, p = 0.032) patients were found to have a significantly higher model for end-stage liver disease scores at the time of listing than non-Hispanic Whites. African Americans had a higher probability of receiving LT relative to non-Hispanic Whites (subdistribution HR: 1.211, 95% CI: 1.051-1.396, and p = 0.008). However, Hispanic race/ethnicity was associated with a lower transplantation probability (subdistribution HR: 0.793, 95% CI: 0.747-0.842, and p < 0.001) and increased waitlist mortality (subdistribution HR: 1.173, CI: 1.052-1.308, and p = 0.004) compared with non-Hispanic Whites. There are significant racial and ethnic disparities in waitlist outcomes of patients with NASH in the US. Hispanic patients are less likely to receive LT and more likely to die while on the waitlist compared with non-Hispanic Whites despite being listed with a lower model for end-stage liver disease scores.

Topical Ripasudil for the Treatment of Segmental Corneal Edema: A Case Series.

PURPOSE: Ripasudil, a rho-kinase inhibitor, has gained popularity as an adjunctive therapy after Descemet stripping only to hasten visual recovery. Ripasudil has been shown to increase corneal endothelial cell proliferation and intercellular adhesion, and decrease endothelial cell apoptosis. We present 4 cases in which persistent corneal edema after various anterior segment surgeries was successfully treated with topical ripasudil, and 1 case in which corneal edema did not improve with use of ripasudil. METHODS: Retrospective chart review revealed 5 patients treated with topical ripasudil for persistent corneal edema that failed to improve with conventional, nonsurgical treatments. RESULTS: In each case, the patient had symptomatic, persistent, focal corneal edema which followed a surgical procedure in the anterior segment. The various etiologies of corneal edema included graft failure after Descemet stripping endothelial keratoplasty, a failed penetrating keratoplasty, and 3 cases of pseudophakic corneal edema. These patients experienced improved vision and partial or complete resolution of corneal edema after 2 to 4 weeks of topical ripasudil administered 4 times daily. One patient with pseudophakic bullous keratopathy had edema that initially improved on topical ripasudil, but after cessation of the medication, developed progressive corneal edema and required endothelial keratoplasty. CONCLUSIONS: In patients with focal corneal edema resulting from surgical trauma to the endothelium who failed to clear over time with conservative measures, topical ripasudil was shown to be an effective treatment option that in most cases improved vision and helped reduce the need for endothelial transplantation.

The impact of case complexity in resident-performed cataract surgery.

PURPOSE: To evaluate the association of capsular dye and/or a pupil expansion device (PED) usage on the rate of major complication in resident-performed cataract extraction. METHODS: Resident cataract surgeries between 2016 and 2019 were included. The primary outcomes were anterior or posterior vitrectomy (AVx and PPVx). Cases were grouped by the use of a PED and/or capsular staining along with additional preoperative risk factors. RESULTS: Of the 1,348 cases, 371 (27.5%) documented capsular staining ("Dye-only"), 91 (6.8%) required pupil expansion ("PED-only"), and 100 (7.4%) used both capsular stain and a PED ("Both"). The remainder of cases (n=786, 58.3%) were classified as "Routine." Compared to the "Routine" group, "PED-only" and "Both" had significantly higher odds of an AVx (OR=2.90, 95% CI 1.27-6.19, P=0.01) and/or a PPVx (OR=2.33, 95% CI 1.07-5.12, P=0.04). Among the PPVx cases, the "PED-only" group has significantly higher odds than "Routine" and "Dye-only" (OR=4.64, 95% CI 1.68-12.79, P=0.01; and OR=6.48, 95% CI 1.7-25.0, P=0.005, respectively). In case-control analysis, vision, intraocular pressure, anterior chamber depth, axial length, cataract type, or severity had no significant overall association with complication. When compared to nuclear sclerotic cataract, posterior subcapsular (OR=7.86, 95% CI 1.46-42.47, P=0.017) and white/mature cataracts (OR=3.05, 95% CI 1.1-8.43, P=0.032) had increased odds of complication. CONCLUSION: Resident-performed cataract surgery frequently required capsular staining and/or a PED, and intuitively, these cases had a higher overall complication rate compared to routine cases. However, the use of a PED independently was associated with significantly higher odds of a major complication requiring an unplanned vitrectomy independent of predisposing factors.

De novo metabolic syndrome after liver transplantation: a meta-analysis on cumulative incidence, risk factors, and outcomes.

Post-transplant metabolic syndrome (PTMS) has been associated with increased cardiovascular risk which significantly impacts the morbidity and mortality rates of liver transplant (LT) recipients. This study sought to conduct a meta-analysis and systematic review on the cumulative incidence, risk factors, and cardiovascular outcomes associated with de novo PTMS.Medline and Embase were searched for articles describing the incidence, risk factors, and cardiovascular outcomes of de novo PTMS. Meta-analysis of proportions was conducted to calculate incidence. Conventional pairwise analysis using random effects model was used to tabulate OR and hazard ratio for risk factors and cardiovascular outcomes, respectively. Fifteen studies involving 2683 LT recipients were included. Overall rate of de novo PTMS was 24.7% (CI: 18.0%-32.9%) over a mean follow-up period of 15.3 months and was highest in patients with NAFLD (60.0%, CI: 52.0%-67.5%) compared with other liver diseases. Older age (OR: 1.05, CI: 1.01-1.09, p = 0.02) and pre-LT type II diabetes mellitus (OR: 5.00, CI: 4.17-5.99, p < 0.01) were predictive factors of de novo PTMS. Patients with de novo PTMS had significantly higher likelihood of cardiovascular disease events compared with those who did not (hazard ratio: 2.42, CI: 1.54-3.81, p < 0.01). De novo PTMS is a common complication and is significantly associated with increased cardiovascular disease morbidity. High-risk patients such as elderly recipients, those with pre-LT type II diabetes mellitus, or NASH-related cirrhosis should undergo routine screening to allow timely intervention.

Performance of Vibration-Controlled Transient Elastography and Clinical Prediction Models In Liver Transplant Recipients.

Hepatic fibrosis is a strong predictor of clinical outcomes following liver transplantation (LT).1 Despite the centrality of hepatic fibrosis in clinical outcomes, the published literature with noninvasive fibrosis assessment in LT recipients is limited and liver biopsy, despite its invasive nature, remains the reference standard. Vibration-controlled transient elastography (VCTE) and clinical prediction models (CPM) are point-of-care tests that can provide noninvasive assessment of hepatic fibrosis2-4; however, the data comparing the diagnostic performance of VCTE and CPM in LT recipients are lacking. The current study evaluated the diagnostic performance of VCTE and CPM in LT recipients using best practices in regulatory sciences for biomarker development.

Evaluation of liver stiffness measurement-based scores in liver transplantation recipients.

Combining bioclinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration-controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplantation (LT) recipients. Thus, the aim of this study was to evaluate the diagnostic performance of combining LSM-based scores with LSM alone for the detection of advanced fibrosis in LT recipients. Adult LT recipients with a liver biopsy, VCTE, and clinical data necessary to construct LSM-based fibrosis models (FibroScan-AST [FAST], AGILE-3+, and AGILE-4) were included ( n = 132). The diagnostic statistics for advanced fibrosis (fibrosis stage 0-2 vs. 3-4) were determined by optimal cut-off using the Youden index. The area under the receiver operating characteristic curve (AUROC) for LSM was 0.94 (95% confidence interval [95% CI], 0.89-0.99), FAST was 0.65 (95% CI, 0.50-0.79), AGILE-3+ was 0.90 (95% CI, 0.83-0.97), and AGILE-4 was 0.90 (95% CI, 0.83-0.97). No statistically significant differences were noted between the AUROC of LSM versus LSM-based scores. The false-positive rates for AGILE-3+ and AGILE-4 were 14.5% and 11.8% compared with 8.3% for LSM alone. The false-positive rates in LSM-based scores were higher among patients with diabetes mellitus, higher AST levels, and lower platelet counts. The LSM-based scores did not improve the diagnostic performance of LSM alone in LT recipients for the detection of advanced fibrosis. This lack of improvement in diagnostic performance results from the impact of immunosuppression on bioclinical profile and underscores the importance of developing LSM-based scores that are specific to LT patients.

The Spectrum and Impact of Metabolic Dysfunction in MAFLD: A Longitudinal Cohort Analysis of 32,683 Overweight and Obese Individuals.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) was recently proposed as an alternative name change for better encapsulation of disease. However, there exists a spectrum of MAFLD where both metabolically healthy (MH) and metabolically unhealthy (MU) individuals are included. In view of limited evidence, we sought to examine the prevalence, clinical characteristics, and differences in outcomes of MH-MAFLD at the population level. METHODS: Data were used from the United States National Health and Nutrition Examination Survey 1999 to 2018. Multivariate logistic regression analysis was used to obtain odds ratios for the estimation of events. Survival analysis was conducted with Cox regression and the Fine-Gray subdistribution model. RESULTS: There were 32,683 overweight and obese individuals included in the analysis. In MAFLD patients, the prevalence of MH-MAFLD was 6.92% (95% confidence interval [CI], 6.58%-7.27%), and 93.08% (95% CI, 92.73%-93.42%) were considered as MU-MAFLD. Multivariate analysis found a significantly higher risk of MACE (odds ratio, 1.38; 95% CI, 1.28-1.49; P < .01), all-cause (hazard ratio, 1.24; 95% CI, 1.17-1.32; P < .01), cardiovascular disease (SHR, 1.20; 95% CI, 1.02-1.42; P = .03), and cancer mortality (SHR, 1.24; 95% CI, 1.07-1.44; P < .01) in MU-MAFLD relative to non-MAFLD. However, MH-MAFLD individuals were not associated with a statistically significant increased risk of these adverse outcomes compared with non-MAFLD. MU-MAFLD diabetics were also at a higher risk of adverse events compared with non-diabetics. CONCLUSIONS: This study reports on the heterogeneity and spectrum of metabolic dysfunction that exists in overweight and obese MAFLD. Although MAFLD may potentially be advantageous in improving awareness and patient outcomes, there remains substantial heterogeneity within patients included in MAFLD on the basis of the underlying metabolic burden.

Colon Adenocarcinoma Metastasis Through Ileocolic Fistula to Small Bowel in the Setting of Crohn's Disease.

Patients with Crohn's disease are at higher risk of developing colorectal cancer and gastrointestinal fistula. Few cases in the past described colorectal cancer metastasized within the gastrointestinal tract through a fistula. We report a case of sigmoid colon adenocarcinoma in a patient with Crohn's disease that metastasized to the ileum through an ileocolic fistula tract. In addition to presenting a unique pathological phenomenon in these patients, this case raises awareness of the importance of regular follow-up and early initiation of inflammatory bowel disease therapies.

DEXA Scan Body Fat Mass Distribution in Obese and Non-Obese Individuals and Risk of NAFLD-Analysis of 10,865 Individuals.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide yet predicting non-obese NAFLD is challenging. Thus, this study investigates the potential of regional fat percentages obtained by dual-energy X-ray absorptiometry (DXA) in accurately assessing NAFLD risk. Using the United States National Health and Nutrition Examination Survey (NHANES) 2011−2018, multivariate logistic regression and marginal analysis were conducted according to quartiles of regional fat percentages, stratified by gender. A total of 23,752 individuals were analysed. Males generally showed a larger increase in marginal probabilities of NAFLD development than females, except in head fat, which had the highest predictive probabilities of non-obese NAFLD in females (13.81%, 95%CI: 10.82−16.79) but the lowest in males (21.89%, 95%CI: 20.12−23.60). Increased percent of trunk fat was the strongest predictor of both non-obese (OR: 46.61, 95%CI: 33.55−64.76, p < 0.001) and obese NAFLD (OR: 2.93, 95%CI: 2.07−4.15, p < 0.001), whereas raised percent gynoid and leg fat were the weakest predictors. Ectopic fat deposits are increased in patients with non-obese NAFLD, with greater increases in truncal fat over gynoid fat. As increased fat deposits in all body regions can increase odds of NAFLD, therapeutic intervention to decrease ectopic fat, particularly truncal fat, may decrease NAFLD risk.

Historical Changes in Weight Classes and the Influence of NAFLD Prevalence: A Population Analysis of 34,486 Individuals.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally in tandem with the growing obesity epidemic. However, there is a lack of data on the relationship between historical weight changes 10 years ago and at present on NAFLD prevalence at the population level. Therefore, we sought to evaluate the relationship between weight classes and the prevalence of NAFLD. Methods: Data were used from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Univariate and multivariate general linear model analyses were used to obtain risk ratio (RR) estimations of NAFLD events. Results: In total, 34,486 individuals were analysed, with those who were lean at both time points as the control group. Overweight (RR: 14.73, 95%CI: 11.94 to 18.18, p < 0.01) or obese (RR: 31.51, 95%CI: 25.30 to 39.25, p < 0.01) individuals at both timepoints were more likely to develop NAFLD. Residual risk exists where previously obese individuals became overweight (RR: 14.72, 95%CI: 12.36 to 17.52, p < 0.01) or lean (RR: 2.46, 95%CI: 1.40 to 4.31, p = 0.02), and previously overweight individuals who became lean (RR 2.24, 95%CI 1.42 to 3.54, p = 0.01) had persistent elevated risk of developing NAFLD despite weight regression. Sensitivity analysis identified that a higher proportion of individuals with regression in weight class were diabetics and Mexican Americans, while fewer African Americans saw weight-class regression. Conclusions: Residual risk exists in patients who lost weight despite the smaller magnitude of effect, and targeted weight reductions should still be used to mitigate the risk of NAFLD at the population level.

Cerium dioxide, a Jekyll and Hyde nanomaterial, can increase basal and decrease elevated inflammation and oxidative stress.

It was hypothesized that the catalyst nanoceria can increase inflammation/oxidative stress from the basal and reduce it from the elevated state. Macrophages clear nanoceria. To test the hypothesis, M0 (non-polarized), M1- (classically activated, pro-inflammatory), and M2-like (alternatively activated, regulatory phenotype) RAW 264.7 macrophages were nanoceria exposed. Inflammatory responses were quantified by IL-1ß level, arginase activity, and RT-qPCR and metabolic changes and oxidative stress by the mito and glycolysis stress tests (MST and GST). Morphology was determined by light microscopy, macrophage phenotype marker expression, and a novel three-dimensional immunohistochemical method. Nanoceria blocked IL-1ß and arginase effects, increased M0 cell OCR and GST toward the M2 phenotype and altered multiple M1- and M2-like cell endpoints toward the M0 level. M1-like cells had greater volume and less circularity/roundness. M2-like cells had greater volume than M0 macrophages. The results are overall consistent with the hypothesis.