Defining comprehensive models of care for NAFLD

Non-alcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease globally. Despite the increased demand placed on health-care systems, little attention has been given to the design and implementation of efficient and effective models of care for patients with NAFLD. In many health-care settings, no formal pathways exist and, where pathways are in place, they are often not standardized according to good practices. We systematically searched the peer-reviewed literature with the aim of identifying published examples of comprehensive models of care that answered four key questions: what services are provided? Where are they provided? Who is offering them? How are they coordinated and integrated within health-care systems? We identified seven models of care and synthesized the findings into eight recommendations nested within the ‘what, where, who and how’ of care models. These recommendations, aimed at policy-makers and practitioners designing and implementing models of care, can help to address the increasing need for the provision of good practice care for patients with NAFLD

Case report: a unique pediatric case of a primary CD8 expressing ALK-1 positive anaplastic large cell lymphoma of skeletal muscle

Primary involvement of skeletal muscle is a very rare event in ALK-1 positive anaplastic large cell lymphoma (ALCL). We describe a case of a 10-year old boy presenting with a three week history of pain and a palpable firm swelling at the dorsal aspect of the left thigh. Histological examination of the lesion revealed a tumoral and diffuse polymorphic infiltration of the muscle by large lymphoid cells. Tumor cells displayed eccentric, lobulated "horse shoe" or "kidney-shape" nuclei. The cells showed immunohistochemical positivity for CD30, ALK-1, CD2, CD3, CD7, CD8, and Perforin. Fluorescence in situ hybridization analysis revealed a characteristic rearrangement of the ALK-1 gene in 2p23 leading to the diagnosis of ALK-1 positive ALCL. Chemotherapy according to the ALCL-99-NHL-BFM protocol was initiated and resulted in a complete remission after two cycles. This case illustrates the unusual presentation of a pediatric ALCL in soft tissue with a good response to chemotherapy

Neurofibromatosis 1 - mutant microglia exhibit sexually-dimorphic cyclic AMP-dependent purinergic defects

As critical regulators of brain homeostasis, microglia are influenced by numerous factors, including sex and genetic mutations. To study the impact of these factors on microglia biology, we employed genetically engineered mice that model Neurofibromatosis type 1 (NF1), a disorder characterized by clinically relevant sexually dimorphic differences. While microglia phagocytic activity was reduced in both male and female heterozygous Nf1 mutant (Nf1+/-) mice, purinergic control of phagocytosis was only affected in male Nf1+/- mice. ATP-induced P2Y-mediated membrane currents and P2RY12-dependent laser lesion-induced accumulation of microglial processes were also only impaired in male, but not female Nf1+/-, microglia. These defects resulted from Nf1+/- male-specific defects in cyclic AMP regulation, rather than from changes in purinergic receptor expression. Cyclic AMP elevation by phosphodiesterase blockade restored the male Nf1+/- microglia defects in P2Y-dependent membrane currents and process motility. Taken together, these data establish a sex-by-genotype interaction important to microglia function in the adult mouse brain

Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice

Background & Aims: Non-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings. / Methods: A survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas. / Results: There were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median = 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of 7.5 to >20 kPa, respectively). / Conclusions: The cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management. / Lay summary: Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD

Cardiovascular risk categories in patients with nonalcoholic fatty liver disease and the role of low-density lipoprotein cholesterol

Cardiovascular disease (CVD) is the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). The current analysis expands the knowledge on atherogenic lipid profiles in NAFLD by modeling changes in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) in a prospectively enrolling real-life study cohort to inform physicians on the cardiovascular (CV) event risk based on these changes. A total of 304 patients with histologically confirmed NAFLD were included (mean age, 52 years; equal sex distribution). Of these, 129 (42.4%) patients exhibited a NAFLD activity score ≥4 and 186 (61.2%) had at least intermediate fibrosis ≥F2. The median TC levels were 209 mg/dL (interquartile range [IQR], 183, 239), LDL-C 131 mg/dL (IQR, 103, 152), and high density lipoprotein cholesterol (HDL-C) 45 mg/dL (IQR, 38, 52). Only 16.9% of patients received lipid-lowering therapy. According to the LDL/HDL ratio, 69 (23.7%) patients exhibited a high CV risk. The 10-year CV event risk according to the Framingham risk score (FRS) was low in 91 (41.2%), intermediate in 59 (26.7%), and high in 71 (32.1%) patients and higher in the ≥F2 NAFLD population. A moderate increase in LDL-C levels by 20 mg/dL led to a transition of 20% of patients into the high-risk group when assessing the LDL/HDL ratio. According to the FRS, 6 (2.7%) patients moved from low to intermediate and 11 (4.9%) from intermediate to high CV risk. Conclusion: Patients with NAFLD exhibit a substantial CV event risk and are frequently undertreated with lipid-lowering medication. Moderate increases in LDL-C would result in worsening of the CV event risk in approximately 7.8% of all patients without a history of CVD. E

The role of echocardiography and CT in the diagnosis of cardiac tumors

A young male who presented with atypical chest pain was found to have a primary cardiac tumor. Chest X-ray, electrocardiogram, and echocardiographic findings can be nonspecific. Differential diagnosis and the role of different diagnostic modalities including echocardiogram, computerized tomography and magnetic resonance imaging are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42542/1/10554_2005_Article_BF01801645.pd

Administrative Coding in Electronic Health Care Record-Based Research of NAFLD: An Expert Panel Consensus Statement

cited By 0Background and Aims Electronic health record (EHR)-based research allows the capture of large amounts of data, which is necessary in NAFLD, where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Diseases (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues. Approach and Results Researchers with an interest in EHR-based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR-based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research. Conclusions This expert panel consensus statement can help harmonize and improve generalizability of EHR-based NAFLD research.Peer reviewe

Advancing the global public health agenda for NAFLD: a consensus statement

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics — from epidemiology, awareness, care and treatment to public health policies and leadership — that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD

Machine learning approaches to enhance diagnosis and staging of patients with MASLD using routinely available clinical information

\ua9 2024 McTeer et al.Aims Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) outcomes such as MASH (metabolic dysfunction associated steatohepatitis), fibrosis and cirrhosis are ordinarily determined by resource-intensive and invasive biopsies. We aim to show that routine clinical tests offer sufficient information to predict these endpoints. Methods Using the LITMUS Metacohort derived from the European NAFLD Registry, the largest MASLD dataset in Europe, we create three combinations of features which vary in degree of procurement including a 19-variable feature set that are attained through a routine clinical appointment or blood test. This data was used to train predictive models using supervised machine learning (ML) algorithm XGBoost, alongside missing imputation technique MICE and class balancing algorithm SMOTE. Shapley Additive exPlanations (SHAP) were added to determine relative importance for each clinical variable. Results Analysing nine biopsy-derived MASLD outcomes of cohort size ranging between 5385 and 6673 subjects, we were able to predict individuals at training set AUCs ranging from 0.719-0.994, including classifying individuals who are At-Risk MASH at an AUC = 0.899. Using two further feature combinations of 26-variables and 35-variables, which included composite scores known to be good indicators for MASLD endpoints and advanced specialist tests, we found predictive performance did not sufficiently improve. We are also able to present local and global explanations for each ML model, offering clinicians interpretability without the expense of worsening predictive performance. Conclusions This study developed a series of ML models of accuracy ranging from 71.9—99.4% using only easily extractable and readily available information in predicting MASLD outcomes which are usually determined through highly invasive means