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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome. The clinicopathologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Simple steatosis has a relatively benign clinical course, but NASH can progress to cirrhosis and hepatocellular carcinoma. As yet there is no convincingly effective treatment for NAFLD and the best option for these patients might be a multimodal treatment plan targeting obesity, insulin resistance, diabetes mellitus, hyperlipidemia and hypertension.
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PMID:[Treatment of fatty liver disease]. 1840 89

Steatosis of the liver may arise from a variety of conditions, but the molecular basis for lipid droplet formation is poorly understood. Although a certain amount of lipid storage may even be hepatoprotective, prolonged lipid storage can result in an activation of inflammatory reactions and loss of metabolic competency. Apart from drug-induced steatosis, certain metabolic disorders associated with obesity, insulin resistance, and hyperlipidemia give also rise to nonalcoholic fatty liver diseases (NAFLD). It is noteworthy that advanced stages of nonalcoholic hepatic steatosis and steatohepatitis (NASH) result ultimately in fibrosis and cirrhosis. In this regard, the lipid droplets (LDs) have been discovered to be metabolically highly active structures that play major roles in lipid transport, sorting, and signaling cascades. In particular, LDs maintain a dynamic communication with the endoplasmic reticulum (ER) and the plasma membrane via sphingolipid-enriched domains of the plasma membrane-the lipid rafts. These microdomains frequently harbor receptor tyrosine kinases and other signaling molecules and connect extracellular events with intracellular signaling cascades. Here, we review recent knowledge on the molecular mechanisms of drug and metabolically induced hepatic steatosis and its progression to steatohepatitis (NASH). The contribution of cytokines and other signaling molecules, as well as activity of nuclear receptors, lipids, transcription factors, and endocrine mediators toward cellular dysfunction and progression of steatotic liver disease to NASH is specifically addressed, as is the cross-talk of different cell types in the pathogenesis of NAFLD. Furthermore, we provide an overview of recent therapeutic approaches in NASH therapy and discuss new as well as putative targets for pharmacological interventions.
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PMID:Molecular mechanisms and therapeutic targets in steatosis and steatohepatitis. 1892 66

Non-alcoholic fatty liver disease includes a broad spectrum of liver abnormalities ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Patients with primary NASH have the metabolic (or insulin resistance) syndrome, condition typically associated with obesity, diabetes, hyperlipidemia and hypertension. To understand the mechanisms implicated in development of NASH, animal models of non-alcoholic fatty liver disease have been generated. These have greatly improved our understanding of some of the aspects of this disease. The challenge now is to identify the common mechanisms between the animal models and humans, which could eventually lead to a better prognosis and development of novel therapeutic strategies.
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PMID:Non-alcoholic steatohepatitis and animal models: understanding the human disease. 1902 69

Nonalcoholic steatohepatitis (NASH), which is the most severe histological form of nonalcoholic fatty liver disease, is emerging as the most common clinically important form of liver disease in developed countries. Although its prevalence is 3% in the general population, this increases to 20-40% in obese patients. Since NASH is associated with obesity, its prevalence has been predicted to increase along with the growing epidemic of obesity and type 2 diabetes mellitus. The importance of this observation comes from the fact that NASH is a progressive fibrotic disease in which cirrhosis and liver-related death occur in 25 and 10% in these patients, respectively, over a 10-year period. This is of particular concern given the increasing recognition of NASH in the developing world. Treatment consists of treating obesity and its comorbidities: diabetes and hyperlipidemia. Nascent studies suggest that a number of pharmacological therapies may be effective, but all remain unproven at present. Histological and laboratory improvement occurs with a 10% decrease in bodyweight. Bariatric surgery is indicated in selected patients. A greater understanding of the pathophysiological progression of NASH in obese patients must be obtained in order to develop more focused and improved therapy.
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PMID:Obesity, hepatic metabolism and disease. 1934 75

This article reviews evidence that causally links hormonal disorders with hepatobiliary disease, and gives particular focus to nonalcoholic steatohepatitis (NASH). The downstream mechanisms by which endocrine disturbances cause liver disease might be similar to those involved in the development of primary liver disease. Hypothyroidism, for example, might lead to NASH, cirrhosis and potentially liver cancer via the development of hyperlipidemia and obesity. Patients with growth hormone deficiency have a metabolic-syndrome-like phenotype that is also associated with the development of NASH. Polycystic ovary syndrome is a common endocrine disorder that is often associated with insulin resistance, the metabolic syndrome, altered levels of liver enzymes and the development of NASH. Recent findings support a role of dehydroepiandrosterone sulfate deficiency in the development of advanced NASH. In addition, adrenal failure is increasingly reported in patients with end stage liver disease and in patients who have received a liver transplant, which suggests a bidirectional relationship between liver and endocrine functions. Clinicians should, therefore, be aware of the potential role of endocrine disorders in patients with cryptogenic liver disease and of the effects of liver function on the endocrine system.
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PMID:Endocrine and liver interaction: the role of endocrine pathways in NASH. 1934 15

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and may progress to advanced hepatic fibrosis and cirrhosis in some patients. Cirrhosis due to NAFLD is considered extremely rare in children in the Asia-Pacific region. We report the characteristics of 5 children with advanced hepatic fibrosis and cirrhosis due to NAFLD. Four of them were obese, and all of them had high alanine transaminase levels and ultrasonographic evidence of fatty liver. None had diabetes mellitus or hyperlipidemia. The calculated HOMA-IR was more than two in all five cases. Liver biopsy showed stage III fibrosis in 2 patients and stage IV fibrosis (cirrhosis) in 3.
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PMID:Advanced hepatic fibrosis and cirrhosis due to nonalcoholic fatty liver disease in Sri Lankan children: a preliminary report. 1966 6

Non-alcoholic fatty liver disease (NAFLD) has recently been recognized as a leading cause of abnormal liver function tests. Its spectrum ranges from simple steatosis, which is usually a benign and non progressive condition, to non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis and hepatocellular carcinoma. NASH is thought to be almost 10% of NALFD and part of metabolic syndrome. NASH patients usually have insulin resistance, frequently combined with hypertension, hyperlipidemia and diabetes. The etiology of NASH remains unclear, but most investigators agree that the development of NASH requires underlying steatosis followed by a "second hit" that induces inflammation, fibrosis, or necrosis. The interaction of adipocytokines (TNF-alpha, adiponectin) with oxidative stress and lipid peroxidation has been postulated to play a key role in NASH. The basic therapy for NASH is an improved of lifestyle, including exercise and diet. Drug therapy should be considered as additional therapy.
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PMID:[Diagnosis and therapy in NASH]. 1986 Feb 10

1. In 13 dogs used repeatedly as donors for plasmapheresis and plasma injection experiments and fed a kennel diet that for a period of over a year consisted chiefly of bones with much adherent fat, cirrhosis of the liver occurred in 10. Marked fatty change without definite fibrosis occurred in 2 of the dogs. 2. In control dogs fed the same kennel diet during the same period but not subjected to repeated bleedings, no instance of cirrhosis was observed. 3. In previous plasmapheresis and plasma injection experiments "donor dogs" subjected to similar bleedings over comparable periods but maintained on a different kennel diet did not develop cirrhosis. 4. This series of events suggests that in dogs maintained on a relatively high fat diet repeated bleedings predispose them to cirrhosis of the liver. No data are available to decide the more fundamental question: Do the repeated bleedings remove something (other than hemoglobin) necessary for continued integrity of the liver, or is the cirrhosis the result of relative anoxia or increased lipemia occasioned by the repeated bleedings or perhaps of both combined?
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PMID:CIRRHOSIS OF THE LIVER IN "DONOR" DOGS FED A HIGH FAT DIET AND SUBJECTED TO REPEATED BLEEDINGS. 1987 65

Nonalcoholic fatty liver disease (NAFLD), first described in 1980, is now recognized as one of the most common causes of elevated liver enzymes and chronic liver disease in Western countries. The incidence of NAFLD in both adults and children is rising, in conjunction with the burgeoning epidemics of obesity and type 2 diabetes mellitus. NAFLD often coexists with other sequelae of the metabolic syndrome: central obesity, type 2 diabetes, hypertension, and hyperlipidemia. NAFLD encompasses a spectrum of pathologic liver diseases ranging from simple hepatic steatosis to a predominant lobular necro-inflammation, with or without centrilobular fibrosis (called nonalcoholic steatohepatitis or NASH). NASH can progress to cirrhosis, decompensated liver disease, and hepatocellular carcinoma. Though the natural history of NASH is still not clearly defined, it has been observed to progress to cirrhosis in 15%-220% of those affected. Insulin resistance is nearly universal in NASH and is thought to play an important role in its pathogenesis leading to dysregulated lipid metabolism. The prevalence of insulin resistance is reported in the general population to be approaching 45%, suggesting that NAFLD and NASH will contin nue to be an important public health concern. To date, NASH has proven to be a difficult disease to treat. Front-line therapy with lifestyle modifications resulting in weight loss through decreased caloric intake and moderate exercise is generally believed to be beneficial in patients with NASH, but is often difficult to maintain long term. Given that insulin resistance plays a dominant role in the pathogenesis, many studies have examined the use of insulin sensitizers: the biguanides (metformin), thiazolidinediones (pioglitazone, troglitazone, and rosiglitazone), glucagon-like peptide-1-receptor agonists, or incretins (exenatide)in NASH. This review will provide an overview of insulin resistance in NAFLD and provide a detailed summary on the clinical data regarding the use of insulin sensitizers in NASH.
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PMID:Insulin sensitizers in nonalcoholic fatty liver disease and steatohepatitis: Current status. 1992 Nov 18

Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become a common entity in clinical practice. In most of the patients it presents as simple steatosis with nonprogressive clinical course. However, some patients have progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), and are at increased risk of developing cirrhosis and hepatocellular carcinoma. NAFLD treatment includes lifestyle modifications and pharmacotherapy aiming at increasing insulin sensitivity, and attenuating inflammation and hepatic fibrosis. Weight reduction has consistently been shown to reduce levels of liver enzymes and insulin resistance. Although dietary intervention and exercise remain the first-line therapy, due to low patients compliance to these measures pharmacotherapy or surgical approaches are often required. Metformin and thiazolidinediones may improve insulin sensitivity, serum aminotransferase level and liver histology. However, little evidence exists regarding their sustained effects after drug discontinuation which, together with their side effects, limits their widespread use in clinical practice. Statins appear to be safe agents for the treatment of hyperlipidemia, although trials documenting their efficacy in NAFLD are scarce. Based on the recent clinical trials, weight loss medication orlistat, ursodeoxycholic acid and antioxidant agents could potentially be used as adjunctive therapy. Considering still largely controversial clinical data regarding pharmacological agents, their high cost and known side-effects, lifestyle modifications at present remain the only essential considerations in the NAFLD treatment.
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PMID:Therapy of nonalcoholic fatty liver disease: current status. 2038 46


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