The silent burden of non-alcoholic fatty liver disease in the elderly: A global burden of disease analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The growing trend towards an aging population, along with an alarming rise in obesity and diabetes, may have significant implications for the burden of NAFLD. AIM: To assess the impact of NAFLD on the elderly. METHODS: We utilised data from the Global Burden of Disease study between 2010 and 2019 to conduct a comprehensive analysis of the prevalence, mortality, and disability-adjusted life years (DALYs) associated with NAFLD in the elderly (65-89 years), stratified by region, nation, sociodemographic Index and sex. RESULTS: Globally, there were an estimated 228 million cases, 87,230 deaths and 1.46 million DALYs attributed to NAFLD in the elderly. Geographically, the Western Pacific region had the highest burden of NAFLD in the elderly. From 2010 to 2019, there was an increasing prevalence rate in all areas, with the most pronounced change observed in the Western Pacific region (annual percentage change (APC) +0.95%, p < 0.001). Over the study period, there was a more rapid increase in NAFLD prevalence in men (APC +0.74%, p < 0.001) than in women (APC +0.63%, p < 0.001). In most regions, death and DALYs rates have declined, with the exception of the Americas, where there was a slight increase (APC +0.25%, p = 0.002 and 0.38%, p < 0.001, respectively). CONCLUSION: Over the past decade, the burden of NAFLD in the elderly has been increasing, necessitating immediate and inclusive measures to tackle the rising burden.

Quality Assessment of Ultrasound and Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance: A Systematic Review and Meta-Analysis.

INTRODUCTION: To achieve early detection and curative treatment options, surveillance imaging for hepatocellular carcinoma (HCC) must remain of quality and without substantial limitations in liver visualization. However, the prevalence of limited liver visualization during HCC surveillance imaging has not been systematically assessed. Utilizing a systematic review and meta-analytic approach, we aimed to determine the prevalence of limited liver visualization during HCC surveillance imaging. METHODS: MEDLINE and Embase electronic databases were searched to identify published data on liver visualization limitations of HCC surveillance imaging. An analysis of proportions was pooled using a generalized linear mixed model with Clopper-Pearson intervals. Risk factors were analysed using a generalized mixed model with a logit link and inverse variance weightage. RESULTS: Of 683 records, 10 studies (7,131 patients) met inclusion criteria. Seven studies provided data on liver visualization limitations on ultrasound (US) surveillance exams: prevalence of limited liver visualization was 48.9% (95% CI: 23.5-74.9%) in the overall analysis and 59.2% (95% CI: 24.2-86.9%) in a sensitivity analysis for cirrhotic patients. Meta-regression determined that non-alcoholic fatty liver disease was associated with limited liver visualization on US. Four studies provided data for liver visualization limitations in abbreviated magnetic resonance imaging (aMRI), with inadequate visualization ranging from 5.8% to 19.0%. One study provided data for complete MRI and none for computed tomography. CONCLUSION: A substantial proportion of US exams performed for HCC surveillance provide limited liver visualization, especially in cirrhosis, which may hinder detection of small observations. Alternative surveillance strategies including aMRI may be appropriate for patients with limited US visualization.

The global burden of metabolic disease: Data from 2000 to 2019.

Global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were examined for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, and non-alcoholic fatty liver disease [NAFLD]). For metabolic risk factors (hyperlipidemia and obesity), estimates were limited to mortality and DALYs. From 2000 to 2019, prevalence rates increased for all metabolic diseases, with the greatest increase in high socio-demographic index (SDI) countries. Mortality rates decreased over time in hyperlipidemia, hypertension, and NAFLD, but not in T2DM and obesity. The highest mortality was found in the World Health Organization Eastern Mediterranean region, and low to low-middle SDI countries. The global prevalence of metabolic diseases has risen over the past two decades regardless of SDI. Urgent attention is needed to address the unchanging mortality rates attributed to metabolic disease and the entrenched sex-regional-socioeconomic disparities in mortality.

The global syndemic of metabolic diseases in the young adult population: A consortium of trends and projections from the Global Burden of Disease 2000-2019.

BACKGROUND: A significant proportion of premature deaths globally are related to metabolic diseases in young adults. We examined the global trends and mortality of metabolic diseases in individuals aged below 40 years using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. METHODS: From 2000 to 2019, global estimates of deaths and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus [T2DM], hyperlipidemia, hypertension, obesity, non-alcoholic fatty liver disease [NAFLD]). Subgroup analyses were performed based on sex, geographical regions and Socio-Demographic Index (SDI). Age-standardised death and DALYs were presented per 100,000 population with 95 % uncertainty intervals (UI). Projections of mortality and DALYs were estimated using regression models based on the GBD 2019 data and combining them with Institute for Health Metrics and Evaluation projection counts for years up to 2050. RESULTS: In 2019, the highest age-standardised death rates were observed in hypertension (133·88 [121·25-155·73]), followed by obesity (62·59 [39·92-89·13]), hyperlipidemia (56·51 [41·83-73·62]), T2DM (18·49 [17·18-19·66]) and NAFLD (2·09 [1·61-2·60]). Similarly, obesity (1932·54 [1276·61-2639·74]) had the highest age-standardised DALYs, followed by hypertension (2885·57 [2580·75-3201·05]), hyperlipidemia (1207·15 [975·07-1461·11]), T2DM (801·55 [670·58-954·43]) and NAFLD (53·33 [40·73-68·29]). Mortality rates decreased over time in hyperlipidemia (-0·6 %), hypertension (-0·47 %), NAFLD (-0·31 %) and T2DM (-0·20 %), but not in obesity (1·07 % increase). The highest metabolic-related mortality was observed in Eastern Mediterranean and low SDI countries. By 2050, obesity is projected to contribute to the largest number of deaths (102·8 % increase from 2019), followed by hypertension (61·4 % increase), hyperlipidemia (60·8 % increase), T2DM (158·6 % increase) and NAFLD (158·4 % increase), with males continuing to bear the greatest burden across all metabolic diseases. CONCLUSION: The growing burden of metabolic diseases, increasing obesity-related mortality trends, and the sex-regional-socioeconomic disparities evident in young adulthood, underlie the concerning growing global burden of metabolic diseases now and in future.

KMSubtraction: reconstruction of unreported subgroup survival data utilizing published Kaplan-Meier survival curves.

BACKGROUND: Data from certain subgroups of clinical interest may not be presented in primary manuscripts or conference abstract presentations. In an effort to enable secondary data analyses, we propose a workflow to retrieve unreported subgroup survival data from published Kaplan-Meier (KM) plots. METHODS: We developed KMSubtraction, an R-package that retrieves patients from unreported subgroups by matching participants on KM plots of the overall cohort to participants on KM plots of a known subgroup with follow-up time. By excluding matched patients, the opposing unreported subgroup may be retrieved. Reproducibility and limits of error of the KMSubtraction workflow were assessed by comparing unmatched patients against the original survival data of subgroups from published datasets and simulations. Monte Carlo simulations were utilized to evaluate the limits of error of KMSubtraction. RESULTS: The validation exercise found no material systematic error and demonstrates the robustness of KMSubtraction in deriving unreported subgroup survival data. Limits of error were small and negligible on marginal Cox proportional hazard models comparing reconstructed and original survival data of unreported subgroups. Extensive Monte Carlo simulations demonstrate that datasets with high reported subgroup proportion (r = 0.467, p < 0.001), small dataset size (r = - 0.374, p < 0.001) and high proportion of missing data in the unreported subgroup (r = 0.553, p < 0.001) were associated with uncertainty are likely to yield high limits of error with KMSubtraction. CONCLUSION: KMSubtraction demonstrates robustness in deriving survival data from unreported subgroups. The limits of error of KMSubtraction derived from converged Monte Carlo simulations may guide the interpretation of reconstructed survival data of unreported subgroups.

A Diagnostic Test Meta-Analysis Evaluating Imaging-Based and Blood Biomarker-Based Assessment Tools for Fibrosis After Liver Transplantation.

Early detection of liver graft fibrosis is crucial for risk stratification to identify patients for liver biopsy and timely treatment. However, diagnostic accuracy of noninvasive tests (NITs) remains unclear. Thus, this study sought to evaluate diagnostic accuracy of NITs in assessing liver allograft fibrosis and compare the differences in specificities and sensitivities among NITs. Medline and Embase databases were searched to include articles on diagnostic tests in liver transplantation (LT) patients with fibrosis. A meta-analysis on diagnostic test accuracy was conducted in a random-effects model. Sensitivities and specificities among the diagnostic tests were compared, and threshold values were calculated where applicable. A total of 25 articles were included. Vibration-controlled transient elastography (VCTE) met the minimum diagnostic accuracy requirements, yielding sensitivity, specificity, and diagnostic odds ratios of 0.9 (CI, 0.8-1.0), 0.9 (CI, 0.8-1.0), and 379.6 (CI, 45.8-1728.7), respectively. In the threshold assessment, the optimal cutoff was 9.30 kPa with a sensitivity, specificity, and area under the curve of 0.7 (CI, 0.5-0.9), 0.9 (CI, 0.8-0.9), and 0.9 (CI, 0.8-0.9), respectively. For significant fibrosis, acoustic radiation force impulse (ARFI) was superior to FibroTest (LabCorp [Burlington, NC]) and magnetic resonance elastography (MRE) in sensitivity. VCTE was superior to FibroTest in specificity. For advanced fibrosis, ARFI was superior to the Fibrosis-4 Index (FIB-4) in sensitivity. VCTE was superior to the AST to Platelet Ratio Index (APRI), MRE, and FIB-4 in specificity. In cirrhosis, VCTE was superior to APRI in specificity (P = 0.004) with comparable sensitivity. This study demonstrates the potential of VCTE and ARFI as diagnostic tools for fibrosis in LT recipients compared with blood-based NITs, which were shown to be less optimal.

Pharmacogenetic versus clinical dosing of warfarin in individuals of Chinese and African-American ancestry: assessment using data simulation.

BACKGROUND: Clinical trials of genotype-guided dosing of warfarin have yielded mixed results, which may in part reflect ethnic differences among study participants. However, no previous study has compared genotype-guided versus clinically guided or standard-of-care dosing in a Chinese population, whereas those involving African-Americans were underpowered to detect significant differences. We present a preclinical strategy that integrates pharmacogenetics (PG) and pharmacometrics to predict the outcome or guide the design of dosing strategies for drugs that show large interindividual variability. We use the example of warfarin and focus on two underrepresented groups in warfarin research. MATERIALS AND METHODS: We identified the parameters required to simulate a patient population and the outcome of dosing strategies. PG and pharmacogenetic plus loading (PG+L) algorithms that take into account a patient's VKORC1 and CYP2C9 genotype status were considered and compared against a clinical (CA) algorithm for a simulated Chinese population using a predictive Monte Carlo and pharmacokinetic-pharmacodynamic framework. We also examined a simulated population of African-American ancestry to assess the robustness of the model in relation to real-world clinical trial data. RESULTS AND CONCLUSION: The simulations replicated similar trends observed with clinical data in African-Americans. They further predict that the PG+L regimen is superior to both the CA and the PG regimen in maximizing percentage time in therapeutic range in a Chinese cohort, whereas the CA regimen poses the highest risk of overanticoagulation during warfarin initiation. The findings supplement the literature with an unbiased comparison of warfarin dosing algorithms and highlights interethnic differences in anticoagulation control.