Clinical Research Directory

Association Between Metabolic Associated Fatty Liver Disease and Obstructive Sleep Apnea

Association between Metabolic Associated Fatty Liver Disease and Obstructive Sleep Apnea

Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

This study will test a Regeneron study drug called ALN-CIDEB to find out whether it may help treat a liver disease called metabolic dysfunction-associated steatohepatitis (MASH). MASH is more advanced stage of a broader liver disease, MASLD. MASLD is a liver condition caused by too much fat building up in the liver. This can lead to liver scarring and inflammation and can reduce the liver's ability to keep the body healthy. Cell death-inducing DFFA-like effector B (CIDEB) is a protein made by liver cells that helps the liver to store fat. The study is looking at: * What side effects ALN-CIDEB might cause * How well ALN-CIDEB works to change liver fat, liver injury, and liver scarring * How ALN-CIDEB could affect the body and the liver, which can help researchers understand why ALN-CIDEB works better for some people than others

Clinical Profile of Patients With MASLD in Kazakhstan and Clinical Effectiveness of Ursosan in Almaty

This study will look at the health characteristics of adults with metabolic dysfunction-associated steatotic liver disease (MASLD) in Kazakhstan. Researchers want to better understand how this liver condition appears in people in Kazakhstan and how it is managed in everyday medical care. About 420 adults with MASLD will take part. Researchers will collect information from their medical records, laboratory tests, liver imaging, and questionnaires. A smaller group of about 65 participants in Almaty who were already prescribed Ursosan® by their doctor before joining the study will be followed for 6 months. Researchers will look at changes in a liver enzyme called alanine aminotransferase (ALT) and other measures of liver health. The study does not assign Ursosan® or any other treatment. Treatment decisions are made by each participant's doctor as part of their usual medical care. The results may help researchers better understand MASLD in Kazakhstan and how people with MASLD respond to Ursosan® when it is used in everyday medical care.

Study of Grape Consumption in Adaptation to Seasonal Photoperiod

The goal of this randomized clinical trial is to learn whether consuming grapes during their natural season can help the body adapt to the shorter daylight hours of winter. The study includes men and women aged 30-70 years with either normal weight or overweight or obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The main questions it aims to answer are: * Does seasonal grape consumption change circulating microRNAs, small molecules involved in regulating gene activity? * Does grape consumption influence sleep, physical activity, metabolic markers, body composition, muscle function, and gut bacteria during the transition to winter? Within each population group, researchers will compare participants consuming yogurt with freeze-dried grape powder with participants consuming the same yogurt without grape powder. Both groups will receive the same Mediterranean-style dietary guidance. Participants will: * Consume two yogurts daily for 3 weeks, either with or without a total daily dose of 16 grams of freeze-dried grape powder, equivalent to approximately 80 grams of fresh grapes. * Complete a further 2 weeks of follow-up without the grape intervention. * Attend an initial information visit and three assessment visits for blood sampling, stool sample collection, and measurements of body composition and muscle function. * Wear a wrist device to monitor sleep and physical activity. * Complete questionnaires, dietary records, and a sleep diary.

Endohepatology-Based Reclassification of Treatment Indication in High-Risk MASLD

This prospective observational study evaluates whether endohepatology changes treatment indications in adults at high risk of metabolic dysfunction-associated steatotic liver disease. Non-invasive testing is followed, when indicated, by a single-session endohepatology assessment including EUS-guided shear-wave elastography, portal pressure gradient measurement and liver biopsy. The primary outcome is treatment reclassification compared with the prospectively documented non-invasive assessment.

Impact of Live Streaming Exercise on Liver Health in MASLD Pregnant Women

Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) is a clinical and pathological syndrome characterized primarily by excessive intracellular fat accumulation in the liver, excluding alcohol-related and other specific causes. Recent research has identified an association between MASLD and an increased risk of pregnancy-related complications and adverse pregnancy outcomes, including gestational diabetes, preeclampsia, preterm birth, and large-for-gestational-age infants. MASLD in pregnant women poses multiple risks to maternal and infant health. Regular physical exercise during pregnancy has been shown to effectively reduce the incidence of pregnancy complications and adverse outcomes, while also alleviating hepatic steatosis and fibrosis. This study is a randomized controlled trial aimed at exploring the feasibility and effectiveness of online exercise interventions for pregnant women with MASLD, as well as conducting a cost-effectiveness analysis and investigating the underlying physiological mechanisms based on the liver-gut axis. The findings are intended to provide scientific evidence and practical recommendations for managing pregnancy health and intervening in MASLD during pregnancy.

A Study to Estimate Secukinumab Retention Rate in Psoriasis Patients With MASLD

This study aims to examine the retention rate of secukinumab in adult patients with plaque psoriasis (with or without psoriatic arthritis \[PsA\]) and metabolic dysfunction-associated steatotic liver disease (MASLD) in routine clinical practice in Spain, as well as hepatic biomarker trajectories. The study will use electronic medical record (EMR) data from multiple Spanish hospitals.

Samsung S-Viscosity vs Canon Dispersion Slope in Steatotic Liver Disease (SAVID-SLD)

Steatotic liver disease (SLD) is one of the most common chronic liver diseases worldwide. Distinguishing simple steatosis from metabolic dysfunction-associated steatohepatitis (MASH) with significant fibrosis is clinically important, but liver biopsy - the current standard - is invasive. Recent ultrasound technology allows noninvasive measurement of tissue viscoelasticity, which has been linked to liver inflammation. Samsung Medison's R20 system (S-Viscosity) and Canon Aplio i800 (Dispersion Slope Imaging) both provide vendor-specific viscoelasticity parameters derived from shear-wave dispersion analysis, but their relationship and agreement have not been compared in SLD patients. This prospective single-center observational study will enroll approximately 95-100 participants in three cohorts: (A) 15-20 living-donor candidates as a healthy reference, (B+C) approximately 80 adults with sonographically suspected or confirmed SLD recruited consecutively. SLD participants will be classified post-hoc into low-MASH-risk (Cohort B) and at-risk MASH (Cohort C) subgroups using a multi-parametric stratification combining liver stiffness (LSM), DeepUSFF (deep-learning-based ultrasound fat fraction), and serum AST. All participants will undergo same-day ultrasound examination with both Samsung HERA W12 and Canon Aplio i800. The primary objective is to evaluate the correlation and agreement between Samsung S-Viscosity and Canon Dispersion Slope. Secondary objectives include deriving a normal reference range from the healthy cohort, comparing viscoelasticity parameters across cohorts, and exploring a Modified US-FAST score.

Quantitative Ultrasound (RS85 and R20) for Liver Fat Quantification in MASLD Using MRI-PDFF as Reference

This multicenter prospective study aims to evaluate the correlation between quantitative ultrasound fat fraction (USFF) and MRI-PDFF (Proton Density Fat Fraction) for liver fat quantification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). The study will compare the diagnostic accuracy of quantitative ultrasound imaging against MRI-PDFF as the reference standard. ==\> V 4.0: Prospective multicenter study evaluating the correlation between Samsung Medison quantitative ultrasound (DeepUSFF) and MRI-PDFF in patients with MASLD across two ultrasound platforms (RS85 and R20). Total target enrollment 182 participants in two parallel device arms: RS85 arm (n=62; SNUH 31 + US site 31) and R20 arm (n=120; SNUH). Within the R20 arm, a paired-device substudy (n=60) evaluates interplatform reproducibility between R20 and RS85. Secondary objectives include intra- and inter-observer agreement of DeepUSFF on each platform.

A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)

The main purpose of the SYNERGY-OUTCOMES study is to find out whether retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in people with high-risk metabolic dysfunction-associated steatotic liver disease (MASLD). The study will enroll adults who have MASLD based on non-invasive tests (NITs), which indicate they are more likely to develop MALO. Participants will be randomly assigned within a Master Protocol to receive either retatrutide (N1T-MC-RT01), tirzepatide (N1T-MC-TZ01) or placebo. The trial plans to enroll about 4,500 adults and will run for approximately 224 weeks. Participants may have up to approximately 25 to 30 clinic visits throughout the study to monitor their health, complete study procedures, and assess liver function and disease progression. Once the study is complete, eligible participants may participate in an optional 2-year extension study, in which all participants will receive either retatrutide or tirzepatide, even if they received placebo in the main study.

FIB-4 Index, Sleep Apnea Severity, and Nocturnal Hypoxemia

This retrospective study evaluates whether the Fibrosis-4 (FIB-4) index is associated with the severity of obstructive sleep apnea (OSA) and nighttime oxygen desaturation. Adults who underwent full-night polysomnography were grouped according to apnea-hypopnea index (AHI) as no OSA, mild OSA, moderate OSA, or severe OSA. Routine clinical, laboratory, and sleep-study data were reviewed. The main aim is to compare FIB-4 values across OSA severity groups and to examine whether FIB-4 is related to AHI, oxygen desaturation index (ODI), and minimum oxygen saturation during sleep. The study also evaluates the proportion of patients with FIB-4 values at or above 1.30, a commonly used threshold for identifying individuals who may need further liver fibrosis assessment. FIB-4 is used in this study as a noninvasive liver fibrosis risk marker and not as a diagnosis of liver fibrosis.

Impact of Overt and Subclinical Hypothyroidism on Liver Fibrosis in Patients With MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is one of the most common chronic liver conditions globally. The progression of liver fibrosis (scarring) represents the most critical determinant of long-term liver-related morbidity and mortality in these patients. Thyroid hormones play an essential role in hepatic lipid metabolism, and thyroid dysfunction, specifically overt and subclinical hypothyroidism, has been implicated in the development and progression of MASLD. However, evidence regarding whether hypothyroidism independently worsens liver fibrosis severity remains inconsistent. This study aims to investigate the association between overt and subclinical hypothyroidism and the stages of liver fibrosis in adult Egyptian patients with MASLD using non-invasive diagnostic tools. A total of 120 adult patients diagnosed with MASLD attending the outpatient hepatology and endocrinology clinics at Assiut University Hospital will be enrolled, consisting of 60 patients with hypothyroidism and 60 euthyroid controls. All participants will undergo standardized clinical assessments, anthropometric measurements, and laboratory investigations, including thyroid function panels (TSH and free T4), liver function tests, lipid profiles, and glycemic markers. Hepatic steatosis will be evaluated via abdominal ultrasound, while liver fibrosis severity will be assessed using transient elastography (FibroScan) to measure liver stiffness, alongside validated blood-based scoring models (FIB-4 index and NAFLD Fibrosis Score). Comparing these findings across groups will help clarify whether thyroid deficiency acts as an independent contributor to advanced liver fibrosis.

Effects of Different Exercises on Intrahepatic Lipid in Patients With Metabolic Dysfunction-associated Steatotic Liver Disease

This is a single-center, randomized, parallel controlled study to explore the effects of aerobic exercise, resistance exercise or aerobic combined resistance exercise on liver lipid in patients with MASLD, consisting of a 12-week core study followed by a 12-month extension phase.

Fibrosis and Metabolic Markers in Relation to PREVENT Cardiovascular Risk in MASLD

This retrospective observational study evaluates the relationship between non-invasive liver fibrosis and metabolic markers and estimated cardiovascular risk in adults with metabolic dysfunction-associated steatotic liver disease (MASLD). The primary objective is to assess the association between the Fibrosis-4 index (FIB-4) and 10-year cardiovascular disease risk estimated using the American Heart Association PREVENT equations, with particular attention to the effect of age on this association. Secondary analyses evaluate the Fibrosis-3 index (FIB-3), triglyceride-glucose index (TyG), and liver stiffness measurement (LSM) in relation to PREVENT-estimated risks of cardiovascular disease, atherosclerotic cardiovascular disease, and heart failure.

Hypothyroidism and Liver Fibrosis Severity in MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, characterized by excess fat accumulation in the liver associated with metabolic risk factors such as obesity and type 2 diabetes. Over time, MASLD can progress from simple liver fat accumulation to liver inflammation and fibrosis (scar tissue formation), which is the most critical factor predicting long-term liver health complications. Thyroid hormones play a key role in controlling hepatic metabolism and lipid handling. An underactive thyroid gland (hypothyroidism), including both overt and mild (subclinical) forms, has been linked to increased fat accumulation and advanced fibrosis in the liver. However, further evidence is needed regarding how thyroid dysfunction relates to liver fibrosis using modern, non-invasive assessment tools in clinical practice. The primary purpose of this observational case-control study is to evaluate the relationship between hypothyroidism and the severity of liver fibrosis in adult patients with MASLD. Participants diagnosed with MASLD will be categorized into two groups based on thyroid function: patients with hypothyroidism (cases) and patients with normal thyroid function (controls). All participants will undergo standard clinical assessments, routine fasting laboratory tests, thyroid function tests, abdominal ultrasound, and transient elastography (FibroScan) to measure liver stiffness and fibrosis severity non-invasively. Non-invasive fibrosis scores, including the FIB-4 index and the NAFLD Fibrosis Score (NFS), will also be calculated. The findings will help determine whether hypothyroidism is independently associated with more severe liver fibrosis in patients with MASLD, potentially guiding screening and management strategies.

Developing Microbial Therapy for MASLD: From Mechanism to Clinical Validation

Metabolic dysfunction-associated steatotic liver disease (MASLD), redefined in 2020, is an improved diagnostic standard evolved from non-alcoholic fatty liver disease (NAFLD), emphasizing the correlation between hepatic steatosis and metabolic dysfunction. Compared to NAFLD, which relies on exclusion-based diagnosis, MASLD criteria enhance population homogeneity in studies and accommodate patients with coexisting liver diseases, thereby improving the efficiency and relevance of drug development. MASLD affects approximately one-quarter of the global population. If left untreated, it may progress to liver fibrosis, cirrhosis, or hepatocellular carcinoma. Given its high clinical burden and the current lack of FDA-approved therapies, effective treatments for MASLD are urgently needed. Previous studies suggest that diet and gut microbiota play crucial roles in the pathogenesis of MASLD. Dietary composition influences microbial balance and intestinal barrier function. In dysbiosis, gut-derived harmful substances such as pathogen-associated molecular patterns (PAMPs) and microbiota-derived metabolites (MDMs) may translocate via a leaky gut to the liver through the portal vein, contributing to hepatic injury. These processes, often described as the gut-liver axis, remain incompletely understood. Animal studies have shown that dietary components regulating gut microbiota may help alleviate MASLD. While clinical evidence remains limited, incorporating microbiota-modulating and immune-regulating food ingredients holds potential. Next-generation probiotics have demonstrated benefits in improving hepatic lipid metabolism and modulating gut microbiota, potentially slowing MASLD progression through gut-liver axis modulation. Our previous research investigated a pasteurized Akkermansia muciniphila strain, NTUH\_Amuc03 (pAKK\_LWHK0003), which attenuated fatty liver progression in preclinical models. In mice subjected to a high-fat, high-fructose, high-cholesterol diet, pAKK\_LWHK0003 administration resulted in reduced body weight, improved dyslipidemia, lowered NAFLD activity scores, and improved HOMA-IR. These findings support the potential of pAKK\_LWHK0003 in slowing MASLD progression. This study aims to evaluate further the clinical efficacy and safety of pAKK\_LWHK0003 in individuals with MASLD.

Metformin-Dapagliflozin Effects on IGF-1 in Male T2DM With MASLD

This is a 3-month, single-center, prospective, randomized, parallel-controlled, open-label trial investigating the effects of metformin combined with dapagliflozin on serum IGF-1 levels in male patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD). A total of 84 eligible male patients (aged 30-60 years, HbA1c 7.0%-10.0%, CAP ≥248 dB/m, on stable metformin monotherapy for ≥8 weeks) will be randomized 1:1 to either continue metformin alone or receive metformin plus dapagliflozin 10 mg/day for 12 weeks. The primary endpoint is the change in serum IGF-1 from baseline to 3 months between groups. Secondary endpoints include changes in hepatic steatosis (CAP), liver stiffness (LSM), FIB-4 index, metabolic parameters, and safety outcomes. The study aims to determine whether adding dapagliflozin to metformin can restore the suppressed GH-IGF-1 axis and provide mechanistic insights into its hepatoprotective effects.

Prospective Evaluation of Hepatocellular Carcinoma Surveillance in At-Risk Patients (Screening HCC)

This prospective multicenter observational study evaluates the performance of a structured hepatocellular carcinoma (HCC) surveillance program in patients at increased risk of developing liver cancer. Participants will undergo routine surveillance with semiannual abdominal ultrasound reported using the Ultrasound Liver Imaging Reporting and Data System (US LI-RADS) and serum alpha-fetoprotein (AFP) testing as part of standard clinical care. The study aims to assess HCC detection rates, stage at diagnosis, detection of other hepatic malignancies, and the time intervals between detection, diagnosis, and treatment in a real-world setting. Approximately 300 participants will be enrolled and followed for up to 36 months.

Gdue Plus a Hypocaloric Mediterranean Diet in Adults With MASLD

This randomized, double-blind, placebo-controlled study evaluated whether Gdue®, a nutraceutical containing extracts of the brown algae Ascophyllum nodosum and Fucus vesiculosus together with chromium picolinate, could improve metabolic health and liver fat when added to a hypocaloric Mediterranean diet. Adults with metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic syndrome, and moderate-to-severe hepatic steatosis were randomly assigned to receive either Gdue® or a matching placebo for 6 months. All participants received an individualized hypocaloric Mediterranean diet and lifestyle counseling. Body weight, body mass index, waist circumference, blood pressure, blood glucose, insulin resistance, lipid levels, liver enzymes, body composition, and liver steatosis were assessed during the study. Liver steatosis was measured using the controlled attenuation parameter obtained by transient elastography. Safety, tolerability, treatment adherence, and adherence to the Mediterranean diet were also evaluated.

Metabolic Flux Analysis in Metabolic Dysfunction-Associated Steatotic Liver Disease

This prospective, single-center pilot study will evaluate metabolic flux dysregulation in adults with obesity and suspected or confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) who are scheduled for protocol-eligible bariatric surgery at Vanderbilt University Medical Center. Participants will undergo research assessments before surgery, during the planned bariatric surgery encounter, and approximately 6 months after surgery. The study uses non-radioactive stable isotope tracer infusions, serial blood sampling, abdominal MRI/MRE, and research tissue specimens collected only during clinically planned bariatric surgery to quantify hepatic and extrahepatic metabolic fluxes. The primary objective is to determine how hepatic citric acid cycle flux and related metabolic pathways change after bariatric surgery and how these metabolic measures relate to liver fat, liver stiffness, and biopsy-graded MASLD/MASH severity.

Liver Steatosis and Fibrosis in Non-Celiac Wheat Sensitivity Patients: a Prospective Study

Hypothesizing an intestinal barrier impairment as a common pathophysiological substrate of both Non Celiac Wheat Sensitivity (NCWS) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MAFLD), in a retrospective cohort study (data not yet published), demographic, clinical, laboratory and histology data of NCWS patients at the time of diagnosis, were analyzed and compared to control subjects with Irritable Bowel Syndrome/Functional Dyspepsia (IBS/FD) and freshly diagnosed Celiac Disease (CeD). NCWS diagnosis was performed by a double-blind placebo-controlled wheat challenge. Steatosis was confirmed by ultrasound examination. Our retrospective data showed that the frequency of liver of steatosis was lower in NCWS than in IBS patients. In addition, it seems that pre-diagnosis avoidance of wheat in NCWS correlates with protection from steatosis. A subset of NCWS patients, recently exposed to wheat, with clinical features suggesting increased IP, seems to be predisposed to liver steatosis and fibrosis. To validate the results of the retrospective study, the researchers planned the present prospective study, to analyze the prevalence of liver steatosis and fibrosis, evaluated by ultrasound (US) examination, FibroScan analysis \[CAP (Controlled Attenuation Parameter) and LSM (Liver Stiffness Measurement) values\], FIB-4 (Fibrosis-4) index, and NFS \[Non-alcoholic fatty liver disease (NAFLD) Fibrosis Score\], in patients with NCWS at the time of diagnosis, comparing them with two control populations of newly diagnosed IBS/FD and CeD patients.

The Effects of 5-methyltetrahydrofolate Supplementation in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease

To determine the effect of MTHF supplementation on serum folate and homocysteine level, metabolic, nutritional status, liver function, and PPARα and TNFα gene expression in patients with MASLD

Non-Invasive Diagnostic Panel for MASLD in Children With Obesity

This prospective, single-center, two-group observational study evaluates a non-invasive multi-parameter diagnostic panel for metabolic dysfunction-associated steatotic liver disease (MASLD) in children with obesity. A total of 180 children aged 8 to 18 years with a body mass index at or above the 85th percentile for age and sex are planned for enrollment at a single tertiary pediatric center. Each participant attends a single study visit comprising a fasting venous blood sample for serum biomarkers (cytokeratin-18 M30 and M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7, adiponectin, leptin, insulin, and routine biochemistry), abdominal ultrasonography with two-dimensional shear wave elastography, and genotyping of three MASLD-associated variants (PNPLA3 rs738409, TM6SF2 rs58542926, HSD17B13 rs72613567). Participants are classified as MASLD-positive or MASLD-negative according to a guideline-based composite reference standard consisting of ultrasonographic steatosis grading and cardiometabolic risk factor criteria, assessed independently of the candidate index tests. The primary objective is to determine the discriminative performance, expressed as the area under the receiver operating characteristic curve, of a LASSO-regularized logistic regression model combining biomarker, elastography, and genetic predictors. No therapeutic intervention is assigned by the study protocol. Reporting will follow the STARD 2015 statement.

Biomarker Panel for PCOS-Associated Liver Steatosis in Adolescent Girls (COMPASS-pedPCOS)

This single-center, prospective, observational, cross-sectional mechanistic pilot study will evaluate whether polycystic ovary syndrome (PCOS) contributes to hepatic steatosis in adolescent girls independently of adiposity. A total of 150 girls aged 10-18 years will be enrolled into three groups of 50: girls with PCOS and obesity, age- and body mass index-matched girls with obesity but without PCOS, and healthy normal-weight girls. Each participant will undergo a single evaluation comprising anthropometry, clinical and biochemical phenotyping, transient elastography with controlled attenuation parameter and two-dimensional shear wave elastography, and a single venous blood sample. An extended biomarker panel will be measured by enzyme-linked immunosorbent assay (Fetuin-A, fibroblast growth factor 21, adiponectin, visfatin, cytokeratin-18 M30 and M65, soluble CD163, growth differentiation factor 15, 11-ketotestosterone, and 11beta-hydroxyandrostenedione), together with liquid chromatography-tandem mass spectrometry measurement of testosterone and sex hormone-binding globulin, and genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567. The primary objective is to compare hepatic steatosis and the hepatokine/adipokine profile between the PCOS with obesity group and the adiposity-matched obesity control group, adjusting for body mass index z-score, insulin resistance, and free androgen index. No therapeutic intervention is assigned by the study protocol.