Nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that causes severe liver damage, fibrosis, and scarring. Despite its potential to progress to cirrhosis or hepatic failure, approved drugs or treatments are currently unavailable. We developed 4,4-diallyl curcumin bis(2,2-hydroxymethyl)propanoate, also known as 35e, which induces upregulation of mitochondrial proteins including carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II, heat shock protein 60, and translocase of the outer mitochondrial membrane 20...

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is defined as the occurrence of hepatic fat accumulation in patients with negligible alcohol consumption or any other cause of hepatic steatosis. This study aimed to correlate the ultrasound-based diagnosis of MAFLD with the histological diagnosis of nonalcoholic steatohepatitis (NASH) and alanine aminotransferase (ALT) levels in patients with MAFLD. METHODS: This was a hospital-based cross-sectional study of 71 patients with MAFLD diagnosed by ultrasound...

Recent genome-wide association studies have identified a missense variant p.A165T in mitochondrial amidoxime-reducing component 1 (mARC1) that is strongly associated with protection from all-cause cirrhosis and improved prognosis in nonalcoholic steatohepatitis (NASH). The precise mechanism of this protective effect is unknown. Substitution of alanine 165 with threonine is predicted to affect mARC1 protein stability and to have deleterious effects on its function. To investigate the mechanism, we have generated a knock-in mutant mARC1 A165T and a catalytically dead mutant C273A (as a control) in human hepatoma HepG2 cells, enabling characterization of protein subcellular distribution, stability, and biochemical functions of the mARC1 mutant protein expressed from its endogenous locus...

BACKGROUND: Evidence suggests that hepatocyte mitochondrial dysfunction leads to abnormal lipid metabolism, redox imbalance, and programmed cell death, driving the onset and progression of non-alcoholic steatohepatitis (NASH). Identifying hub mitochondrial genes linked to NASH may unveil potential therapeutic targets. METHODS: Mitochondrial hub genes implicated in NASH were identified via analysis using 134 algorithms. RESULTS: The Random Forest algorithm (RF), the most effective among the 134 algorithms, identified three genes: Aldo-keto reductase family 1 member B10 (AKR1B10), thymidylate synthase (TYMS), and triggering receptor expressed in myeloid cell 2 (TREM2)...

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) help manage type 2 diabetes (T2DM) and may have efficacy in steatotic liver disease. Objective: To determine the prevalence and clinical impact of GLP-1 RA use in patients with T2DM and liver disease. Methods: This was a retrospective study of adult patients with T2DM and nonalcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL), or nonalcoholic steatohepatitis (NASH) between 1/1/21-12/31/21. Patients with hepatitis B or C, or on pioglitazone were excluded...

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017...

BACKGROUND AND AIMS: Thyroid hormones are important regulators of hepatic lipid homeostasis and whole-body energy expenditure. Recent evidence suggests that euthyroid individuals with metabolic dysfunction-associated steatohepatitis (MASH) develop intrahepatic hypothyroidism that promotes progression of MASH. METHODS: A literature search was performed with Medline (PubMed), Scopus and Google Scholar electronic databases from inception till March 2024, using the following keywords: hypothyroidism and nonalcoholic fatty liver disease; MASLD and thyroid function; intrahepatic hypothyroidism; TRβ agonists; and resmetirom...

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases...

A novel RG-I pectin-like polysaccharide, YJ3A1, was purified from the flowers of Rosa chinensis and its structure and hepatoprotective effect in vivo and in vitro were investigated. The backbone of this polysaccharide is mainly composed of 1, 4-galactan, 1, 4-linked α-GalpA and 1, 2-linked α-Rhap disaccharide repeating unit attached by 1, 6-linked β-Galp or 1, 5-linked α-Araf on C-4 of the Rhap. Interestingly, oral administration of YJ3A1 significantly ameliorates NASH-associated inflammation, oxidative stress and fibrosis and does not affect the liver morphology of normal mice at a dose of 50 mg/kg...

Mulberry leaf has been recognized as a traditional Chinese medicinal plant, which was distributed throughout the Asia. The aqueous extract of mulberry leaf extract (MLE) has various biologically active components such as polyphenols and flavonoids. However, the inhibitory effect of MLE in hepatocarcinogenesis is poorly understood. In this study, we determined the role of MLE supplementation in preventing hepatocarcinogenesis in a carcinogen-initiated high-fat diet (HFD)-promoted Sprague-Dawley (SD) rat model...

BACKGROUND: Cirrhosis is associated with an increased risk for both bleeding and venous thromboembolic (VTE) complications. The data regarding the impact of etiology of cirrhosis on VTE risk is poorly understood. METHODS: In this retrospective observational analysis of the US Nationwide readmissions database 2019, we identified hospitalized patients who had cirrhosis from alcohol, viral, or nonalcoholic steatohepatitis (NASH) etiologies. We identified patients who had acute VTE, chronic/history of VTE, and portal venous thrombosis (PVT)...

Aim: Endogenous ethanol production emerges as a mechanism of nonalcoholic steatohepatitis, obesity, diabetes and auto-brewery syndrome. Methods: To identify ethanol-producing microbes in humans, we used the NCBI taxonomy browser and the PubMed database with an automatic query and manual verification. Results: 85 ethanol-producing microbes in human were identified. Saccharomyces cerevisiae , Candida and Pichia were the most represented fungi. Enterobacteriaceae was the most represented bacterial family with mainly Escherichia coli and Klebsiella pneumoniae ...

Combined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver and cardiovascular diseases. Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders. However, the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain. In this study, CHL was induced in low-density lipoprotein receptor-deficient (LDLR-/- ) hamsters through an 8-week high-fat and high-cholesterol (HFHC) diet or a 4-month high-cholesterol (HC) diet...

The rs72613567:TA polymorphism in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) has been found to reduce the progression from steatosis to nonalcoholic steatohepatitis. In this study, we sought to define the pathogenic role of HSD17B13 in triggering liver inflammation. Here we find that HSD17B13 forms liquid-liquid phase separation (LLPS) around lipid droplets in the livers of nonalcoholic steatohepatitis patients. The dimerization of HSD17B13 supports the LLPS formation and promotes its enzymatic function...

The current study aimed to evaluate the serum levels of nitric oxide (NO) and adropin in males with non-alcoholic fatty liver disease (NAFLD) induced erectile dysfunction (ED) and NAFLD patients without ED and controls. The current study selected 165 participants from the hepatology department from November 2021 to November 2022. The patients were either suffering from NAFLD with normal liver functions or non-alcoholic steatohepatitis with abnormal liver functions. They were diagnosed by abdominal ultrasonography...

Non-alcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease and a progressive and chronic liver disorder with a significant risk for the development of liver-related morbidity and mortality. The complex and multifaceted pathophysiology of NASH makes its management challenging. Early identification of symptoms and management of patients through lifestyle modification is essential to prevent the development of advanced liver disease. Despite the increasing prevalence of NASH, there is no FDA-approved treatment for this disease...

Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is caused by various factors, including genetic and/or environmental factors, and has complicated pathophysiological features during the development of the disease. NAFLD/NASH is recognized as an unmet medical need, and NAFLD/NASH animal models are essential tools for developing new therapies, including potential drugs and biomarkers. In this review, we describe the pathological features of the NAFLD/NASH rat models, focusing on the histopathology of hepatic fibrosis...

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of conditions, progressing from mild steatosis to advanced fibrosis. Sarcopenia, characterized by decreased muscle strength and mass, shares common pathophysiological traits with NAFLD. An association exists between sarcopenia and increased NAFLD prevalence. However, data on the prevalence of sarcopenia in NAFLD and its impact on the outcomes of NAFLD remain inconsistent. AIM: To analyze the prevalence and outcomes of sarcopenia in patients with NAFLD...

Fatty liver disease (FLD) is a highly prevalent pathological liver disorder. It has many and varied etiologies and has heterogeneous clinical course and outcome. Its proper nomenclature and classification have been problematic since its initial recognition. Traditionally, it was divided into two main categories: Alcohol-associated liver disease and nonalcoholic FLD (NAFLD). Among these, the latter condition has been plagued with nomenclature and classification issues. The two main objections to its use have been the use of negative (non-alcoholic) and stigmatizing (fatty) terms in its nomenclature...

BACKGROUND: Visceral fat represents a metabolically active entity linked to adverse metabolic sequelae of obesity. We aimed to determine if celiac artery mesenteric fat thickness can be reliably measured during endoscopic ultrasound (EUS), and if these measurements correlate with metabolic disease burden. METHODS: This was a retrospective analysis of patients who underwent celiac artery mesenteric fat measurement with endosonography (CAMEUS) measurement at a tertiary referral center, and a validation prospective trial of patients with obesity and nonalcoholic steatohepatitis who received paired EUS exams with CAMEUS measurement before and after six months of treatment with an intragastric balloon...