Forty years of successful national research collaboration in liver disease - the Swedish experience.

Aim: Sweden has historically provided a fruitful arena for research in clinical medicine. We here share 40 years of experience of collaboration in the Swedish hepatology research group (SWEHEP) (https://www.swehep.

Association between longitudinal biomarkers and major adverse liver outcomes in patients with non-cirrhotic metabolic dysfunction-associated steatotic liver disease.

Background And Aims: Noninvasive biomarkers provide prognostic information for the development of major adverse liver outcomes (MALOs) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the predictive value of longitudinal biomarker measurements has not been evaluated. We assessed whether changes in biomarkers could predict incident MALO in MASLD.

Approach And Results: We analyzed a cohort of 1260 patients (71.

Performance of novel collagen turnover biomarkers to detect increased liver stiffness in MASLD.

Background: Cleavage products from collagen formation and degradation hold potential as first-line biomarkers for the risk of advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we evaluated the performance of PRO-C3, PRO-C6, C4M, PRO-C18L, and the clinical score ADAPT (age, diabetes, PRO-C3, and platelet count) to detect patients with an LSM >8 kPa or >12 kPa in comparison to the Fibrosis-4 Index (FIB-4).

Methods: Serum from patients with MASLD (n = 269) from six Swedish University Hospitals was analyzed using enzyme-linked immunosorbent assay-based methods.

Liver fibrosis is associated with left ventricular remodeling: insight into the liver-heart axis.

Objective: In nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers.

Methods: In this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden.

A unified framework for prediction of liver steatosis dynamics in response to different diet and drug interventions.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder, characterized by the accumulation of excess fat in the liver, and is a driving factor for various severe liver diseases. These multi-factorial and multi-timescale changes are observed in different clinical studies, but these studies have not been integrated into a unified framework. In this study, we aim to present such a unified framework in the form of a dynamic mathematical model.

A physiologically-based digital twin for alcohol consumption-predicting real-life drinking responses and long-term plasma PEth.

Alcohol consumption is associated with a wide variety of preventable health complications and is a major risk factor for all-cause mortality in the age group 15-47 years. To reduce dangerous drinking behavior, eHealth applications have shown promise. A particularly interesting potential lies in the combination of eHealth apps with mathematical models.

Activin A levels in metabolic dysfunction-associated steatotic liver disease associates with fibrosis and the PNPLA3 I148M variant.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition worldwide. There is an urgent need to develop new biomarkers to assess disease severity and to define patients with a progressive phenotype. Activin A is a new promising biomarker with conflicting results about liver fibrosis.

Altered probe pressure and body position increase diagnostic accuracy for men and women in detecting hepatic steatosis using quantitative ultrasound.

Objectives: To evaluate the diagnostic performance of ultrasound guided attenuation parameter (UGAP) for evaluating liver fat content with different probe forces and body positions, in relation to sex, and compared with proton density fat fraction (PDFF).

Methods: We prospectively enrolled a metabolic dysfunction-associated steatotic liver disease (MASLD) cohort that underwent UGAP and PDFF in the autumn of 2022. Mean UGAP values were obtained in supine and 30° left decubitus body position with normal 4 N and increased 30 N probe force.

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

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.

Risk of major adverse liver outcomes among first-degree relatives of individuals with MASLD.

Background & Aims: Previous studies have suggested an increased risk of major adverse liver outcomes (MALO) in relatives of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, granular and longitudinal evidence is lacking on the future risk of MALO among family members of individuals with MASLD.

Methods: We identified 3526 first-degree relatives (FDRs) and 11 079 general population comparators to 1328 patients with MASLD diagnosed between 1974 and 2021, with detailed clinical data, including liver histology in 71% of patients.

Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD.

Background & Aims: Long-term studies of the prognosis of NAFLD are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD.

Methods: We conducted a cohort study with data from Swedish university hospitals.

Misclassified Alcohol-related Liver Disease is Common in Presumed Metabolic Dysfunction-associated Steatotic Liver Disease and Highly Increases Risk for Future Cirrhosis.

Background & Aims: Alcohol overconsumption is a risk factor for disease progression in patients with presumed metabolic dysfunction-associated steatotic liver disease (MASLD). How commonly this occurs and how it affects progression to major adverse liver outcomes (MALOs) is not well known.

Methods: We did a register-based cohort study, including all patients with a diagnosis of MASLD in Sweden between 1987 and 2020.

A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol.

Background: Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures.

A multi-scale digital twin for adiposity-driven insulin resistance in humans: diet and drug effects.

Background: The increased prevalence of insulin resistance is one of the major health risks in society today. Insulin resistance involves both short-term dynamics, such as altered meal responses, and long-term dynamics, such as the development of type 2 diabetes. Insulin resistance also occurs on different physiological levels, ranging from disease phenotypes to organ-organ communication and intracellular signaling.

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic.

A Markov model of fibrosis development in nonalcoholic fatty liver disease predicts fibrosis progression in clinical cohorts.

Disease progression in nonalcoholic steatohepatitis (NASH) is highly heterogenous and remains poorly understood. Fibrosis stage is currently the best predictor for development of end-stage liver disease and mortality. Better understanding and quantifying the impact of factors affecting NASH and fibrosis is essential to inform a clinical study design.

Entrustable professional activities (EPAs) for undergraduate medical education - development and exploration of social validity.

Background: The development of entrustable professional activities (EPAs) as a framework for work-based training and assessment in undergraduate medical education has become popular. EPAs are defined as units of a professional activity requiring adequate knowledge, skills, and attitudes, with a recognized output of professional labor, independently executable within a time frame, observable and measurable in its process and outcome, and reflecting one or more competencies. Before a new framework is implemented in a specific context, it is valuable to explore social validity, that is, the acceptability by relevant stakeholders.

Life's Essential 8 and carotid artery plaques: the Swedish cardiopulmonary bioimage study.

Background: To quantify cardiovascular health (CVH), the American Heart Association (AHA) recently launched an updated construct of the "Life's Simple 7" (LS7) score, the "Life's Essential 8" (LE8) score. This study aims to analyse the association between both CVH scores and carotid artery plaques and to compare the predictive capacity of such scores for carotid plaques.

Methods: Randomly recruited participants aged 50-64 years from the Swedish CArdioPulmonary bioImage Study (SCAPIS) were analysed.

Cost-effectiveness analysis of noninvasive tests to identify advanced fibrosis in non-alcoholic fatty liver disease.

Background: Advanced fibrosis is associated with end-stage liver disease (ESLD) and mortality in NAFLD. As treatments specifically targeted at NAFLD are lacking, patient management focuses on surveillance for early detection of complications related to end-stage liver disease. Although current and emerging diagnostic tools for the detection of advanced fibrosis are crucial for surveillance, their added value is unclear.

Changing epidemiology, global trends and implications for outcomes of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common liver disease globally and is currently estimated to affect 38% of the global population. Only a minority of patients with NAFLD will progress to cirrhosis or hepatocellular carcinoma, but from this vast population the total number of patients who are at risk of such severe outcomes is increasing. Worryingly, individuals are increasingly being affected by NAFLD at an earlier age, meaning there is more time for them to develop severe complications.

A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures.

Non-alcoholic fatty liver disease (NAFLD) is a common, progressive liver disease strongly associated with the metabolic syndrome. It is unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide a detailed proteo-transcriptomic map of steatohepatitis and fibrosis during progressive NAFLD.