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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is the most important risk factor associated with non-alcoholic steatohepatitis, which is caused by to impaired insulin activity, overflow of portal triglycerides, and production of inflammatory cytokines; all of these are deleterious to hepatocytes. These phenomena facilitate disruptions in hepatic physiology, as observed in alcoholic hepatitis; however, consumption of this substance is absent. Non-alcoholic steatohepatitis has had a great impact due to the fact that previously, main cases of cryptogenic cirrhosis actually were attributed to this disease. Despite advances in understanding the pathophysiologic process of the disease, there is no better treatment than weight reduction (a combination of diet and exercise). In this issue, we describe the most important topics with regard to non-alcoholic steatohepatitis and the obesity-related process.
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PMID:[Obesity and non-alcoholic steatohepatitis]. 1564 74

In 1980, the term non-alcoholic steatohepatitis was coined to describe a new syndrome occurring in patients who usually were obese (often diabetic) females who had a liver biopsy picture consistent with alcoholic hepatitis, but who denied alcohol use. The causes of this syndrome were unknown, and there was no defined therapy. More than two decades later, this clinical syndrome is only somewhat better understood, and still there is no Food and Drug Administration-approved or even generally accepted drug therapy. Patients with primary non-alcoholic steatohepatitis typically have the insulin resistance syndrome (synonymous with the metabolic syndrome, syndrome X, and so forth), which is characterized by obesity, diabetes, hyperlipidemia, hypertension, and, in some instances, other metabolic abnormalities such as polycystic ovary disease. Secondary non-alcoholic steatohepatitis may be caused by drugs such as tamoxifen, certain industrial toxins, rapid weight loss, and so forth. The cause of non-alcoholic steatohepatitis remains elusive, but most investigators agree that a baseline of steatosis requires a second hit capable of inducing inflammation, fibrosis, or necrosis for non-alcoholic steatohepatitis to develop. Our research group has focused its efforts on the interactions of nutritional abnormalities, cytokines, oxidative stress with lipid peroxidation, and mitochondrial dysfunction in the induction of steatohepatitis, both alcoholic and non-alcoholic in origin. Research findings from other laboratories also support the role of increased cytokine activity, oxidative stress, and mitochondrial dysfunction in the pathogenesis of non-alcoholic steatohepatitis. The objectives of this article are to review the (1) definition and clinical features of non-alcoholic steatohepatitis, (2) potential mechanisms of non-alcoholic steatohepatitis, and (3) potential therapeutic interventions in non-alcoholic steatohepatitis.
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PMID:Mechanisms of non-alcoholic steatohepatitis. 1567 Jun 68

The major pathologic manifestations of alcoholic liver injury have been well described, and include three major lesions: steatosis (fatty liver), steatohepatitis (formerly alcoholic hepatitis), and cirrhosis. Recent attention to the problem of nonalcoholic fatty liver disease (NAFLD) in individuals with obesity, diabetes, and other risk factors has shed light on the mechanisms of cellular injury associated with hepatic steatosis and on the potential pathways to steatohepatitis and cirrhosis. Pathologists need to be familiar with the spectrum of changes seen in steatohepatitis, including hepatocyte ballooning, Mallory bodies, mixed inflammatory cell infiltrates, and a distinctive perivenular and pericellular "chicken-wire" fibrosis. These features and other less common histopathologic lesions in the liver are reviewed and illustrated.
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PMID:Morphology of alcoholic liver disease. 1576 28

Steatohepatitis is pathologically characterized by zone 3-dominant hepatic steatosis with ballooned hepatocytes and Mallory bodies, zone 3 pericellular and perivenular fibrosis with or without bridging fibrosis, and lobular inflammatory cell infiltration. Alcoholic hepatitis is a prototype of this syndrome, but a variety of diseases such as obesity, diabetes mellitus, Wilson disease and hepatitis C could reveal very similar pathological changes in some occasions. Therefore, well defined diseases need to be excluded in the process of differential diagnosis of steatohepatitis. Pathways possibly involved in the development of drug-induced steatohepatitis were categorized into four and outlines of the possible mechanisms involved in the development of this syndrome were proposed in this article.
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PMID:[Drug-induced NASH]. 1676 16

Nonalcoholic steatohepatitis (NASH) is the term used to describe the distinct clinical entity in which the liver biopsy findings are similar to that observed in alcoholic hepatitis, but patients lack a history of significant alcohol consumption. The most widely supported theory implicates insulin resistance as the key mechanism leading first to hepatic steatosis, and next to steatohepatitis. In spite of lacking proof by EBM (evidence based medicine) and effective therapy for NASH, modification of risk factors, such as obesity, hyperlipidemia, and good diabetic control is generally recommended. Although there is no consensus of treatment form, the new drugs which can be useful in NASH treatment are continously tested. The aim of our study is to present current knowledge about nonalcoholic steatohepatitis, focusing on present and being in various phases of clinical trials treatment options.
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PMID:[Nonalcoholic steatohepatitis--current treatment options]. 1696 16

Obesity and insulin resistance accelerate the progression of fibrosis during chronic liver disease. Resistin antagonizes insulin action in rodents, but its role in humans is still controversial. The aims of this study were to investigate resistin expression in human liver and to evaluate whether resistin may affect the biology of activated human hepatic stellate cells (HSCs), key modulators of hepatic fibrogenesis. Resistin gene expression was low in normal human liver but was increased in conditions of severe fibrosis. Up-regulation of resistin during chronic liver damage was confirmed by immunohistochemistry. In a group of patients with alcoholic hepatitis, resistin expression correlated with inflammation and fibrosis, suggesting a possible action on HSCs. Exposure of cultured HSCs to recombinant resistin resulted in increased expression of the proinflammatory chemokines monocyte chemoattractant protein-1 and interleukin-8, through activation of nuclear factor (NF)-kappaB. Resistin induced a rapid increase in intracellular calcium concentration, mainly through calcium release from intracellular inositol triphosphate-sensitive pools. The intracellular calcium chelator BAPTA-AM blocked resistin-induced NF-kappaB activation and monocyte chemoattractant protein-1 expression. In conclusion, this study shows a role for resistin as an intrahepatic cytokine exerting proinflammatory actions in HSCs, via a Ca2+/NF-kappaB-dependent pathway and suggests involvement of this adipokine in the pathophysiology of liver fibrosis.
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PMID:Resistin as an intrahepatic cytokine: overexpression during chronic injury and induction of proinflammatory actions in hepatic stellate cells. 1714 67

Approximately 20% of patients infected with the hepatitis B or C virus (HBV and HCV) develop cirrhosis of the liver. It is essential, especially for preventive purposes, to test for related etiological factors, especially excess alcohol consumption, metabolic syndrome, and obesity. The frequency of these health problems and their hepatic tropism explain these frequent associations. In patients with chronic HBV and HCV, alcohol consumption and metabolic syndrome increase the risk of fibrosis; in those with HCV, they also reduce the likelihood of treatment response. In patients with alcoholic hepatitis, overweight increases cirrhotic risk. If cytolysis persists after the identified factor is controlled, another etiologic factor must be sought and treated. For patients with excess alcohol consumption and similarly those with metabolic syndrome, it is essential to differentiate between dependency, which is more difficult to treat, and other risk situations, for which the efficacy of a brief intervention by the physician has been demonstrated. In this more holistic approach, the physician treats a person with liver disease, rather than just a diseased liver.
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PMID:[Managing comorbidities in hepatology: toward a more holistic medicine]. 1839 58

Alcoholic cirrhosis represents the terminal stage of alcoholic liver disease (ALD) and one of the main causes of death among alcohol abusers. The aim of this review was to provide an update on alcoholic cirrhosis, with an emphasis on recent findings. Increased alcohol consumption in developing countries is expected to increase cirrhosis mortality. There is a need, therefore, to develop new approaches to the prevention of ALD, including more attention to co-factors that may increase risk of ALD (i.e., obesity and diabetes, chronic HCV infection, and smoking). Furthermore, a better understanding of the pathological mechanisms on the basis of alcohol cirrhosis represents a cornerstone in order to develop new pharmacological treatments. Inflammatory and immune responses along with oxidative stress and alterations in adipokine secretion might contribute in different ways to the evolution of alcohol-induced fibrosis/cirrhosis. As of this date, patients with severe alcoholic hepatitis with a Maddrey Discriminant Factor (MDF) 32 should be offered pentoxifylline and/or corticosteroids unless contraindications exist. For ambulatory patients, S-adenosylmethionine (SAMe) may be considered in a motivated patient with nutritional support. Current studies do not support use of anti-tumor necrosis factor (TNF)-alpha antibody. Finally, achieving total alcohol abstinence should represent the main aim in the management of patients affected by any stage of cirrhosis. In the last decades, several drugs able to increase abstinence and prevent alcohol relapse have been evaluated and some of them have obtained approval for alcohol dependence. Patients with alcoholic cirrhosis; however, are usually excluded from such treatments. A recent study demonstrated the efficacy and safety of baclofen in inducing and maintaining alcohol abstinence in cirrhotic alcohol-dependent patients with cirrhosis. All together the information available suggests the need of a multimodal approach in the clinical management of these patients.
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PMID:Understanding and treating patients with alcoholic cirrhosis: an update. 1938 82

Liver dysfunction is a prominent entity in Western medicine that has historically affected patients suffering from chronic viral or alcoholic hepatitis. The incidence of these conditions has not changed dramatically in recent years but the overall number of patients with liver dysfunction has increased considerably with the emergence of the obesity epidemic. Nonalcoholic fatty liver disease (NAFLD) has become increasingly recognized as the most common cause of chronic liver disease in the United States. Although the rate of progression of NAFLD to overt cirrhosis is low, the high prevalence of this condition, combined with the moderate degree of liver dysfunction it engenders, has resulted in a significant increase in the number of patients with liver disease that can be encountered by a surgical practice. Any degree of clinically evident liver disease in a prospective surgical patient should raise concern for the entire surgical team. This particularly applies to intraabdominal surgery whereby the presence of hepatomegaly, portal hypertension, variceal bleeding, and ascites can turn even the most routine operation into a morbid and life-threatening procedure. Nonabdominal surgery avoids some of the technical challenges presented by liver disease but the anesthetic management of a cirrhotic patient still makes any operation potentially more dangerous. In this article, approaches to minimize the risk when surgery becomes necessary in the presence of liver disease are discussed.
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PMID:Surgery in the patient with liver disease. 1994 76

Liver dysfunction is a prominent entity in Western medicine that has historically affected patients suffering from chronic viral or alcoholic hepatitis. The incidence of these conditions has not changed dramatically in recent years but the overall number of patients with liver dysfunction has increased considerably with the emergence of the obesity epidemic. Nonalcoholic fatty liver disease (NAFLD) has become increasingly recognized as the most common cause of chronic liver disease in the United States. Although the rate of progression of NAFLD to overt cirrhosis is low, the high prevalence of this condition, combined with the moderate degree of liver dysfunction it engenders, has resulted in a significant increase in the number of patients with liver disease that can be encountered by a surgical practice. Any degree of clinically evident liver disease in a prospective surgical patient should raise concern for the entire surgical team. This particularly applies to intraabdominal surgery whereby the presence of hepatomegaly, portal hypertension, variceal bleeding, and ascites can turn even the most routine operation into a morbid and life-threatening procedure. Nonabdominal surgery avoids some of the technical challenges presented by liver disease but the anesthetic management of a cirrhotic patient still makes any operation potentially more dangerous. In this article, approaches to minimize the risk when surgery becomes necessary in the presence of liver disease are discussed.
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PMID:Surgery in the patient with liver disease. 1966 20


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