Statins in Non-alcoholic Steatohepatitis.
Ontology highlight
ABSTRACT:
SUBMITTER: Torres-Pena JD
PROVIDER: S-EPMC8652077 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Statins in Non-alcoholic Steatohepatitis.
Torres-Peña Jose D JD Martín-Piedra Laura L Fuentes-Jiménez Francisco F
Frontiers in cardiovascular medicine 20211124
Non-alcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease. The range is extensive, including hepatocellular carcinoma, cirrhosis, fibrosis, fatty liver, and non-alcoholic steatohepatitis (NASH). NASH is a condition related to obesity, overweight, metabolic syndrome, diabetes, and dyslipidemia. It is a dynamic condition that can regress to isolated steatosis or progress to fibrosis and cirrhosis. Statins exert anti-inflammatory, proapoptotic, and antifibrotic effects ...[more]
Similar Datasets
Project description:This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.
| S-EPMC4696068 | biostudies-literature
Project description:While metabolic syndrome and alcohol consumption are the two main causes of chronic liver disease, one of the two conditions is often predominant, with the other acting as a cofactor of morbimortality. It has been shown that obesity and alcohol act synergistically to increase the risk of fibrosis progression, hepatic carcinogenesis and mortality, while genetic polymorphisms can strongly influence disease progression. Based on common pathogenic pathways, there are several potential targets that could be used to treat both diseases; based on the prevalence and incidence of these diseases, new therapies and clinical trials are needed urgently.
| S-EPMC7267467 | biostudies-literature
Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH. The complete database comprised the expression measurements of 18185 genes for liver sample groups: 8 non-alcoholic steatohepatitis (NASH ) and 7 control samples. This dataset is part of the TransQST collection.
2013-04-02 | E-GEOD-37031 | biostudies-arrayexpress
Project description:Alcohol-related liver disease (ARLD) and non-alcoholic fatty liver disease (NAFLD) are leading causes of chronic liver disease globally. Both ARLD and NAFLD are multifactorial and refer to a spectrum of disease severity, ranging from steatosis through steatohepatitis to fibrosis and cirrhosis. Both diseases exhibit substantial inter-patient variation in long-term outcomes and are best considered complex disease traits where genetic and environmental factors interact to mediate disease severity and progression. Here, we briefly review the current literature describing the best validated genetic modifiers that influence severity of these liver conditions, including variants of the genes PNPLA3, TM6SF2 and MBOAT7, which have also been implicated in lipid dysregulation.
| S-EPMC6334028 | biostudies-literature
Project description:The hallmark of non-alcoholic fatty liver disease (NAFLD) is excessive fatty accumulation in the hepatocytes, which may be an isolated event (non-alcoholic fatty liver, NAFL) or accompanied by evidence of inflammation and cell injury with or without fibrosis (non-alcoholic steatohepatitis, NASH). NASH, the more aggressive form of NAFLD, may progress to cirrhosis and hepatocellular carcinoma. Since NASH is estimated to overtake hepatitis C virus infection as the leading cause of liver transplantation in the US in the coming decade, and there are no current FDA-approved therapies for this disease, the need to find appropriate therapeutic targets is now more urgent than ever before. Diet and other lifestyle modifications have always been difficult to maintain and this approach alone has not slowed the rising tide of the disease. While the results of traditional therapies such as vitamin E and pioglitazone have been significant for steatosis and inflammation, they have had no effect on fibrosis, which is the strongest indicator of mortality in this condition. However, the understanding of the pathogenesis and progression of NASH has evolved and several promising novel therapies to target and possibly reverse fibrosis are being evaluated, making the future outlook of NASH therapy more optimistic.
| S-EPMC5492893 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been reported as a novel worldwide epidemic, very often associated with obesity, metabolic syndrome, and type 2 diabetes. Both conditions have also been shown to be associated with a number of endocrine pathologies. Despite the epidemic, the complex pathophysiology and major complications, ranging from metabolic disturbances (diabetes and more) to cardiovascular disease, people with NASH are left with very few management options. The best and most approved therapeutic option is lifestyle intervention. Although pharmacotherapies based on pathophysiological background are in development, response rates appear modest, mainly for fibrosis treatment, which is the reason for lack of approved drug therapy. Previous drugs analyzed, such as pioglitazone and vitamin E, show weak efficacy. From different phase II trials, antidiabetic (injectable) drugs seem to be promising, both in mono- or bitherapy. Also, derivatives of peroxisome proliferator-activated receptors may have an interesting future, as well. For that reason, more focus should be given on prevention of this novel disease entity. In view of this booming epidemic, with a background of obesity and type 2 diabetes, and the important medical consequences, early recognition, prevention and intervention of NAFLD/NASH seems appropriate. In this review, we will focus on the different current and future therapeutic intervention options, taking into consideration the complex pathophysiology of this disease.
| S-EPMC8419532 | biostudies-literature
Project description:Non-alcoholic steatohepatitis (NASH) is the most common cause of liver disease in Western populations, and its prevalence is increasing rapidly. It is part of a multisystem disease affecting other organs such as the kidneys, heart and blood vessels, and is closely associated with the components of the metabolic syndrome. Physicians managing patients with NASH should not only focus on the management of NASH, but also on associated comorbidities in individual patients. The approaches to treatment of NASH include either limiting energy surplus alone, or in combination with targeting of downstream pathways of inflammation and fibrosis. In this mini-review, we discuss the currently available treatment options for NASH, as well as those in late-stage clinical trials. We discuss the challenges of managing these patients with a limited number of approved therapies, as well as managing advanced-stage patients with NASH and cirrhosis. We also discuss the specific management of comorbidities in NASH patients, in particular diabetes, hypertension, dyslipidaemia and cardiovascular diseases. Finally, we present the screening protocols for both hepatocellular carcinoma and extrahepatic malignancies in these patients.
| S-EPMC7654093 | biostudies-literature
Project description:There has been a rise in the prevalence of non-alcohol fatty liver disease (NAFLD) due to the popularity of western diets and sedentary lifestyles. One quarter of NAFLD patients is diagnosed with non-alcoholic steatohepatitis (NASH), with histological evidence not only of fat accumulation in hepatocytes but also of liver cell injury and death due to long-term inflammation. Severe NASH patients have increased risks of cirrhosis and liver cancer. In this review, we discuss the pathogenesis and current methods of diagnosis for NASH, and current status of drug development for this life-threatening liver disease.
| S-EPMC8452937 | biostudies-literature
Project description:SummaryA 72-year-old man with type 2 diabetes volunteered to participate in the control group of a clinical study. The study evaluated non-alcoholic fatty liver disease in patients with kidney disease. The patient was followed at a gastroenterology department due to Crohn's disease and post-operative bile acid malabsorption. The patient had no symptoms or biochemical findings suggesting liver disease. Surprisingly, a transient elastography (FibroScan®) suggested advanced fibrosis with a median of 16.1 kPa. A liver biopsy showed non-alcoholic steatohepatitis (NASH)-cirrhosis. The diagnosis was only made incidentally and highlights how NASH-cirrhosis may be overlooked due to the lack of symptoms.Learning pointsClinicians treating high-risk populations, including patients with type 2 diabetes and/or components of the metabolic syndrome, should be aware of the frequently occurring co-existence with non-alcoholic fatty liver disease (NAFLD) and especially non-alcoholic steatohepatitis (NASH). Liver enzymes may be in the normal range even in people with steatosis, NASH, or even cirrhosis. The diagnosis of NAFLD should include evaluation of hepatic fibrosis as this is the most important prognostic factor for liver-related complications and mortality. Guidelines about systematic screening for NAFLD in patients with type 2 diabetes are incongruent.
| S-EPMC9875068 | biostudies-literature
Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes. There are 12 samples in our study which belonged to 4 groups, and each group contains 3 different samples.
2015-01-23 | E-GEOD-65220 | biostudies-arrayexpress