Non-Alcoholic Fatty Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is an increasingly recognized comorbidity in people living with human immunodeficiency virus (HIV). Chronic low-grade inflammation, altered lipid metabolism, and certain antiretroviral therapy (ART) regimens may heighten the vulnerability of people living with HIV (PLWH) to liver fat accumulation, progressive liver fibrosis, and cardiometabolic complications. The primary purpose of this observational case-control study is to determine the prevalence, clinical characteristics, and laboratory findings of MASLD and hepatic fibrosis among PLWH compared with matched HIV-negative individuals. The study also aims to evaluate dietary quality, lifestyle habits, and cardiovascular risk profiles in both groups, and to determine whether adherence to a healthy lifestyle protects against significant liver disease. Adult participants (aged 18 years and older) attending the Department of Tropical Medicine and Gastroenterology at Assiut University Hospitals will be enrolled into two groups: people living with HIV and HIV-negative individuals matched by age, sex, and degree of liver steatosis. All participants will complete the following non-invasive evaluations: * Hepatic Assessment: Abdominal ultrasound and transient elastography (FibroScan) to detect fatty liver and quantify liver stiffness, alongside non-invasive scoring systems (FIB-4 score and NAFLD Fibrosis Score). * Laboratory Investigations: Fasting blood tests including liver function tests, lipid profiles, glycemic status (HbA1c), kidney function, complete blood count, and immune markers (CD4+ T-cell count and CD4/CD8 ratio). * Physical and Body Measurements: Measurement of body mass index (BMI), waist circumference, and mid-arm muscle circumference (MAMC). * Dietary and Lifestyle Questionnaires: Validated assessment tools including the Food Frequency Questionnaire (FFQ), Short Healthy Eating Index (sHEI), and Healthy Lifestyle Questionnaire to quantify nutritional quality, physical activity, and daily lifestyle habits. * Cardiometabolic Risk Calculation: Calculation of predicted cardiovascular risk using the American Heart Association PREVENT risk score. Findings from this study are intended to clarify the role of dietary quality and lifestyle factors in liver and metabolic health among people living with HIV, potentially informing proactive screening and management strategies.

A randomized, controlled study of standard soy milk consumption compared to 2% fat cow's milk consumption in children with Non-alcoholic Fatty Liver Disease (NAFLD). The investigators hypothesize that the daily consumption of soy isoflavones found in the soy milk will be beneficial in reducing NAFLD and other obesity-related comorbidities. The investigators do not expect any adverse endocrine or metabolomic effects from the consumption of soy isoflavones.

Metabolic Dysfunction-Associated steatotic Liver Diseases MASLD affects approximately 25 percent of population. Systemic inflammation plays role in MASLD progression. This cross-sectional observational study at Assiut University Hospitals will include 180 participants aged 18 to 65 years divided into 90 with MASLD and 90 without MASLD over one year. Nutritional indices Prognostic Nutritional Index PNI and Controlling Nutritional Status CONUT score will be calculated from albumin lymphocyte count and cholesterol. CBC-based inflammatory indices SIRI SII PIV PWR PLR MPR WNR NLR will be calculated. MASLD fibrosis score based on age BMI diabetes AST ALT ratio platelet albumin and FibroScan will assess fibrosis F0-F2 versus F3-F4. Aim to evaluate correlation between PNI CONUT and MASLD and role of inflammatory indices as predictors for MASLD and advanced fibrosis.

Elevated liver enzymes are common laboratory abnormalities that may result from alcohol-related liver disease, drug-induced liver injury, or non-alcoholic fatty liver disease (NAFLD). Persistent elevation of liver enzymes may indicate ongoing hepatocellular injury and increase the risk of progressive liver disease. Current management primarily focuses on treating the underlying cause and providing supportive care, while evidence for effective hepatoprotective therapies remains limited. This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy and safety of Misocholic Tab, a film-coated herbal medicine, in adults with mild to moderate elevation of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) associated with alcohol-related liver disease, drug-induced liver injury, or non-alcoholic fatty liver disease. Eligible participants will be randomly assigned in a 1:1 ratio to receive either Misocholic Tab or matching placebo for 30 days. Both groups will receive standard background therapy with silymarin. The primary objective is to compare the change in serum ALT and AST levels from baseline to Day 30 between the two treatment groups. Secondary objectives include evaluating the proportion of participants whose liver enzyme levels return to the normal range and assessing the safety of Misocholic Tab through clinical evaluation, laboratory testing, and monitoring of adverse events.

This study will evaluate the safety and tolerability of Efimosfermin Alfa for participants with known or suspected MASH with fibrosis consistent with stage F2 or F3.

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.

It is an observational study of non alcoholic fatty liver disease (NAFLD) patients with a calculated sample size of 500. Liver biopsy proved NAFLD patients will be recruited in this study for 10 years follow-up. Patients will be assessed at baseline, at every six months for blood count, liver function test, fasting blood-glucose, fasting insulin, ferritin, liver ultrasonography, and liver stiffness.

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.

The goal of this clinical trial is to understand how the blood sugar-lowering hormone insulin works in healthy adults versus those who are at risk for type 2 diabetes. The study will use a drug called alpelisib, which interferes with insulin's actions in the body, to answer the study's main question: does the liver continue to respond to insulin's stimulation of fat production even when it loses the ability to stop making glucose (sugar) in response to insulin. Researchers will compare the impact of single doses of both alpelisib and placebo (inert non-drug) in random order (like flipping a coin) in study participants. Participants will be asked to stay twice overnight in the hospital, take single doses of alpelisib and placebo (one or the other on each of the two hospital stays), and receive intravenous (into the vein) infusions of non-radioactive "tracer" molecules that allow researchers to measure the production of glucose (sugar) and fats by the liver. Measurements will be done both while participants are fasting (not eating or drinking other than water) and while consuming a standardized diet of nutritional beverages. The objective is to evaluate the effect of lowering insulin levels, while maintaining constant mild hyperglycemia, on plasma glucose and lipid levels.

This research study is creating a way to collect and store specimens and information from participants who may be at an increased risk of developing cancer, or has been diagnosed with an early phase of a cancer or a family member who has a family member with a precursor condition for cancer. * The objective of this study is to identify exposures as well as clinical, molecular, and pathological changes that can be used to predict early development of cancer, malignant transformation, and risks of progression to symptomatic cancer that can ultimately be fatal. * The ultimate goal is to identify novel markers of early detection and risk stratification to drive potential therapeutic approaches to intercept progression to cancer.

In this study the investigators will quantitate hepatic mitochondrial fluxes in T2D patients with NAFL and NASH before and after 16-weeks treatment with the insulin sensitizer pioglitazone

Background: In non-alcoholic fatty liver disease (NAFLD), fat accumulates in the liver and can cause damage. Researchers want to learn what causes the damage NAFLD, and to see if a medication can help. Objective: To find out how the liver in people with NAFLD responds to feeding, and how this relates to their response to the drug semaglutide. Eligibility: People with NAFLD and healthy volunteers ages 18 and older Design: Participants will be screened with: Medical history Physical exam Blood tests Imaging: A machine will take pictures of the participant s body. Within 2-8 weeks of enrollment, participants will stay in the clinic for several days. This includes: Blood, urine, heart, and imaging tests For NAFLD participants only: A needle-like device will remove a small biopsy of the liver and fatty tissue. Participants will be alone in a special room for 5 hours. They will breathe through a tube under the nostrils. They will have blood drawn several times. The baseline visit concludes participation for healthy volunteers but NAFLD participants will contine. About 6 weeks after discharge, participants will stay in the clinic again and repeat the tests. They will get their first semaglutide dose by injection. Participants will have visits weeks 1, 2, 4, 8, 12, 16, 20, and 24 of treatment. Visits include blood tests. Participants will inject semaglutide once a week at home. At week 30, participants will stay in the clinic again and repeat the tests. Participants will have a final visit 12 weeks after stopping treatment. This includes blood and urine tests. ...

The goal of this study is to evaluate the role of transcription factor EB (TFEB) in adipose (fat) tissue macrophages (ATM) in regulating adipose tissue and systemic metabolic function in obesity. The investigators will assess the differences in ATM lipid metabolism in people with metabolically abnormal obesity and lean individuals. Both groups will have: * screening visit * imaging (body composition testing - dual-energy x-ray absorptiometry (DEXA) scans, magnetic resonance imaging \[MRI\] and magnetic resonance spectroscopy \[MRS\] scans) * Overnight visit with intravenous infusion (IV), muscle, and fat tissue biopsies

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), a major global public health concern, is commonly associated with obesity, diabetes, and dyslipidemia. MASLD is currently the most common cause of chronic liver disease affecting about 80% of people with obesity, ranging from simple fat deposits in the liver to Metabolic Dysfunction-Associated Steatohepatitis (MASH), cellular injury, advanced fibrosis, cirrhosis, or hepatocellular carcinoma. Patients with MASH are also at risk for cardiovascular disease and mortality. There is no universally approved medication for MASH. Weight loss remains the cornerstone of MASH treatment. Patients meeting the inclusion and exclusion criteria and who give informed consent will be enrolled in the trial and undergo the baseline liver biopsy (if none available). Approximately 120 patients with MASH and liver fibrosis (F1-F4 in baseline liver biopsy) will be randomized in a 1:1 ratio to metabolic surgery or medical treatment (incretin-based therapies ± other medical therapies for MASH) and followed for 2 years at which time a repeat liver biopsy will be performed for the assessment of the primary end point.

Nonalcoholic steatohepatitis (NASH) is now recognised as an increasing clinical problem in children. Steatosis without significant liver cell injury or fibrosis is the most common form of nonalcoholic fatty liver disease (NAFLD) in both adults and children. Studies in the adult population have variably suggested that steatosis is a benign nonprogressive condition and NASH is recognised as a potentially serious condition with significantly risk of morbidity and mortality. A growing body of evidence suggests that children with NASH frequently show histopathological features that differ from those of adults. The prevalence of this pattern in a wide range of paediatric cases as well as other histopathological lesions and their relevance and prognostic significance in children with NAFLD remains to be determined. Thus the investigators would like to conduct a study of biopsies and clinical information to document the histological features of paediatric NAFLD, to explore the natural history of paediatric NAFLD, and to determine the frequency and prognostic value of these features.

The purpose of this study is to assess the safety and efficacy of efimosfermin alfa in the resolution of steatohepatitis and improvement of liver-related clinical outcome compared to placebo in individuals with MASH and biopsy-confirmed F2- or F3-stage fibrosis.

This is a two-arm, prospective, controlled observational pilot clinical study aimed at characterizing the lipidomic profile and extracellular vesicles (EVs) of patients with autoimmune hepatitis (AIH) compared to patients with non-alcoholic fatty liver disease (NAFLD). A total of 24 adult outpatients will be enrolled at the Hepatology Outpatient Unit of IRCCS "S. de Bellis". Blood samples will be collected by venipuncture to perform lipidomic analyses on red blood cell membranes and serum, and to isolate and characterize EVs. No intervention beyond standard clinical practice will be applied

The purpose of this study is to evaluate the safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of efimosfermin in participants with metabolic dysfunction associated steatohepatitis (MASH) and compensated cirrhosis consistent with stage F4 fibrosis.

The goal of this clinical trial is to compare a one-week course of diazoxide (2 mg/kg per dose x 14 doses) and placebo in people with obesity and insulin resistance (IR) with metabolic dysfunction-associated steatotic liver disease (MASLD). The main question it aims to answer are how mitigation of compensatory hyperinsulinemia with diazoxide affects hepatic de novo lipogenesis, a major contributor to MASLD pathophysiology. Participants will: * Take 14 doses of placebo over 7 days, followed 4-12 weeks later by either 14 doses of diazoxide (at 2 mg per kg of body weight per dose \[mpk\]) or another 14 doses of placebo, over 7 days * Take 18 doses of heavy (deuterated) water (50 mL each) over 7 days, twice * Have blood drawn and saliva collected after an overnight fast on four mornings over the course of the study * Undergo insulin suppression tests (IST) to assess the degree of insulin resistance at the end of each 1-week study period * Consume their total calculated daily caloric needs as divided into three meals per day Researchers will compare blood tests at the beginning and end of each 1-week study period in participants randomized (like the flip of a coin) to receive either placebo followed by diazoxide or placebo followed by placebo, to see how the drug treatment affects de novo lipogenesis, serum insulin, plasma glucose, and other serum lipid parameters (triglycerides, free fatty acids), among others.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. While weight loss through lifestyle modification is the standard treatment, most patients regain weight limiting ultimate improvement in liver disease. On the other end of the spectrum, bariatric surgery has shown promise in the treatment of MASLD/metabolic dysfunction-associated steatohepatitis (MASH) due to its efficacy in inducing weight loss. Nevertheless, its adoption has been hindered by the perceived invasiveness of surgery. Over the past decade, endoscopic sleeve gastroplasty (ESG) has gained recognition as a promising minimally-invasive approach to weight loss. The procedure involves utilizing a Food and Drug Administration (FDA)-authorized endoscopic suturing device to reduce the gastric volume by 70%. Studies reveal that ESG is associated with approximately 18.2% weight loss at one year after the procedure, with sustained results for at least 10 years. Nevertheless, the effect of ESG on MASH remains unknown. In this study, the investigators will compare ESG + lifestyle modification versus lifestyle modification alone in treating histologic MASH. The study will randomize patients to one of two different treatment options: ESG + lifestyle modification or lifestyle modification alone.

The investigators recently demonstrated a increase in liver fat in early middle-aged LBW compared to normal birth weight (NBW) men, and 20% of the LBW - but none of the normal birth weight (NBW) - men had previously unknown non-alcoholic fatty liver disease (NAFLD). Here the investigators will further examine the Increased risk of non-alcoholic fatty liver disease in low birth weight individuals by performing a validation study.

This study is designed to study the pharmacokinetic (PK) and safety profiles of a single dose of efimosfermin alfa in participants with varying degrees of Hepatic Impairment (HI) (assessed by Child-Pugh score) due to steatotic liver disease, with and without significant alcohol consumption.

To identify key characteristics of the tissue resident and peripherally circulating immune-phenotype in addition to blood markers, metabolic profile, faecal and oral microbiota in non-alcoholic fatty liver disease

Chronic liver disease (CLD) is a major cause of global mortality and morbidity . CLD patients are at an increased risk of developing liver fibrosis (formation of scar tissue), cirrhosis and liver failure and are at significant risk to develop primary liver cancer. Non-alcoholic fatty liver disease (NAFLD) represents a major risk for CLD and it is becoming the most common chronic liver condition with an estimated 25% global prevalence. Progression to non-alcoholic steatohepatitis (NASH) occurs in approx. 1 of 5 NAFLD patients and due to the rapidly rising etiology of end-stage liver disease, is currently the second most common etiology of hepatocellular carcinoma (HCC) requiring liver transplantation. Liver biopsy, currently the gold-standard for grading disease activity and staging fibrosis, is invasive, costly and at risk for sampling error. Due to the number of patients diagnosed with fibrosis and since fibrosis stage is prognostic of mortality and drives patient management, it is important to develop noninvasive yet accurate diagnostic tools that can identify fibrosis stage. The purpose of this study is to obtain a panel of clinically well characterized blood specimens to identify novel biomarkers to be used as an aid in diagnosis to assess the stage of clinically significant hepatic fibrosis in patients with signs or symptoms of NAFLD (NAFL/NASH). In addition, quantitative ultrasound (QUS) based approaches combined with artificial intelligence (AI) algorithms will be explored for assessing the stage of fibrosis.

additive efficacy of physical activity program in hypthyroidism in elder females with glaucoma and fatty liver issues was not investigated