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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To date, histologic evaluation, most commonly in the form of liver biopsy, remains the gold standard in evaluation of nonalcoholic fatty liver disease (NAFLD). Histologic evaluation was fundamental to the initial studies that introduced and defined the concept of fatty liver as a liver disease. Currently, liver biopsy in NAFLD serves multiple roles: confirmation (or exclusion) of the diagnosis; distinction of steatohepatitis from "simple steatosis"; assessment of extent of necroinflammatory activity, fibrosis, and architectural alterations. Histopathologic studies have underscored the fact that not all obese and/or diabetic individuals with elevated liver tests have fatty liver disease; for example, hepatic glycogenosis and hepatosclerosis have been described in diabetics, and other significant liver diseases have been documented. Likewise biopsy studies have documented lesions of steatosis or steatohepatitis in unusual patient groups or clinical settings, such as lean individuals, individuals with normal liver tests, patients taking certain medications, patients with co-existent serologically-diagnosed liver disease, and pediatric patients. Biopsy studies have shown that the lesions of NASH may or may not persist in cirrhosis; prior evidence of NASH on liver biopsy serves as a benchmark for the concept that many cases of otherwise cryptogenic cirrhosis developed from NAFLD/NASH. Liver biopsy remains a significant feature of studies delineating long-term outcome of NAFLD, some of which have shown that "simple steatosis" is not always non-progressive and benign. Finally, investigators have noted correlations of proposed pathophysiologic processes in NASH with particular histologic features. Therapeutic trials for NASH rely on histologic evaluation as the most sensitive analysis to document effects of treatment. Treatment trials afford an opportunity to evaluate histologic features of resolution, and these trials have also provided an opportunity for correlations of particular histologic lesions with clinical and laboratory features in well-characterized patient populations. These kinds of studies are currently relatively few, but results of a recent study have reinforced the concept of necessary criteria for diagnosis. Current discussions in pathology include identification of lesions of concern for progression, reproducible methods of diagnosis and semiquantification of lesions, and appropriate nomenclature. Matteoni et al. proposed NAFLD types 1-4 based on long-term outcome studies; Brunt et al. proposed a system of grading and staging for NASH that follows methods of separate assessment for necroinflammatory lesions (grade) and fibrosis (stage) accepted in other forms of non-biliary chronic liver disease. Recently, the Pathology Committee of the NIDDK NASH Clinical Research Network has proposed a system of evaluation that encompasses the entire spectrum of NAFLD from steatosis to steatohepatitis with fibrosis for use in upcoming treatment trials. And, just as the clinician cannot distinguish steatosis and steatohepatitis, the pathologist cannot discern if alcohol abuse may be an underlying cause of the lesions. Proposed nomenclature to align with either extant terminology in other forms of chronic liver disease, or to align with our knowledge of underlying cause(s) (such as metabolic syndrome) will be discussed.
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PMID:Pathology of nonalcoholic steatohepatitis. 1621 95

Non-alcoholic steatohepatitis has been recognized as a significant cause of end-stage liver disease and hepatic decompensation. Despite the growing interest in this condition, the molecular mechanisms underlying the development of fibrosis in this setting are only partially understood. In this article, the cellular and molecular basis of fibrosis in chronic liver disease are briefly outlined. In addition, mechanisms specifically operating in the context of fatty liver and steatohepatitis are examined, including: insulin resistance, oxidative stress, and inflammation. Finally, recent developments indicating the possible contribution of cytokines derived from adipose tissue (adipokines) to liver fibrosis is discussed.
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PMID:Review article: the pathogenesis of fibrosis in non-alcoholic steatohepatitis. 1622 72

Insulin resistance (IR) is the pathophysiological hallmark of nonalcoholic fatty liver disease (NAFLD), one of the most common causes of chronic liver disease in Western countries. We review the definition of IR, the methods for the quantitative assessment of insulin action, the pathophysiology of IR, and the role of IR in the pathogenesis of chronic liver disease. Increased free fatty acid flux from adipose tissue to nonadipose organs, a result of abnormal fat metabolism, leads to hepatic triglyceride accumulation and contributes to impaired glucose metabolism and insulin sensitivity in muscle and in the liver. Several factors secreted or expressed in the adipocyte contribute to the onset of a proinflammatory state, which may be limited to the liver or more extensively expressed throughout the body. IR is the common characteristic of the metabolic syndrome and its related features. It is a systemic disease affecting the nervous system, muscles, pancreas, kidney, heart, and immune system, in addition to the liver. A complex interaction between genes and the environment favors or enhances IR and the phenotypic expression of NAFLD in individual patients. Advanced fibrotic liver disease is associated with multiple features of the metabolic syndrome, and the risk of progressive liver disease should not be underestimated in individuals with metabolic disorders. Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing IR in the liver (metformin) and in the periphery (thiazolidinediones) are discussed.
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PMID:Insulin resistance: a metabolic pathway to chronic liver disease. 1662 42

Liver biopsy has historically played a central role in the diagnosis and management of a variety of chronic liver diseases. However, as the understanding of disease pathology has progressed, and laboratory diagnostics, imaging technology, and clinical algorithms to determine both the etiology and presence of fibrosis have advanced, the role of liver biopsy has become more circumscribed. In chronic liver disease, liver biopsy is now more often used selectively, rather than routinely, for diagnostic purposes. Newer treatment of chronic hepatitis B and C has become more effective and thus reduced the routine need to acquire tissue. Risk factors for nonalcoholic fatty liver disease are readily identified and suggest the diagnosis after exclusion of alternative considerations, and there is no specific treatment for this condition; thus there is little role for the routine use of liver biopsy to guide treatment. Only in select cases of chronic hepatitis C, especially in patients with genotype 1, an indeterminate stage and grade of disease on noninvasive evaluation, or in those with human immunodeficiency virus coinfection, for whom the risks and benefits of treatment are less clear, is there a role for routine pretreatment biopsy.
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PMID:Role of liver biopsy in the management of chronic liver disease: selective rather than routine. 1636 15

In 3 children with chronic liver disease, although multiple studies of copper metabolism were normal, which made the diagnosis of Wilson disease unlikely, analysis of ATP7B gene showed disease causing mutations in all. Molecular diagnosis should be considered in children with enigmatic liver disease, especially those with features of nonalcoholic fatty liver disease.
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PMID:Direct diagnosis of Wilson disease by molecular genetics. 1642 15

Cryptogenic cirrhosis (CC), literally meaning cirrhosis of obscure or unknown origin, is a diagnosis of exclusion. The circumstantial evidence indicates that nonalcoholic fatty liver disease (NAFLD) is perhaps one of the important causes of CC. There is also evidence, especially from the European literature, that some patients with CC may have undiagnosed or burnt-out autoimmune hepatitis (AIH). Other rare causes may include "unknown" viral (non-A, non-B, non-C) hepatitis, and occult alcoholism. In this review, we examine the role of NAFLD and other causes in the pathogenesis of CC, and the impact of obesity on patients with chronic liver disease.
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PMID:Cryptogenic cirrhosis and NAFLD: are they related? 1646 22

Nonalcoholic fatty liver disease (NAFLD) is a diagnostic consideration among patients with asymptomatic elevated aminotransaminases, patients with radiologic findings of hepatic fatty infiltration, or occasionally in the patient with "cryptogenic" cirrhosis. The diagnosis of NAFLD requires evidence of fatty infiltration of the liver in the absence of excessive alcohol ingestion. Clinical evaluation should examine for metabolic risk factors (central obesity, glucose intolerance, hypertension, hypertriglyceridemia, and low HDL cholesterol), which are suggestive but not specific for the diagnosis of NAFLD. Secondary causes of NAFLD, such as medications and intestinal bypass surgery, should be excluded as management of these conditions may differ. Confirmation of hepatic steatosis can usually be done by imaging studies, although occasionally liver biopsy is required. Among suspected NAFLD patients with chronically elevated aminotransaminases, clinical evaluation and serological testing should be performed to exclude other causes of chronic liver disease. Liver biopsy is required to stage fibrosis and distinguish between nonalcoholic steatohepatitis and steatosis. This is valuable for providing prognosis, excluding other liver disease, monitoring response to therapy or evaluating disease progression over time. Clinical features, particularly diabetes, obesity, and older age, can aid in stratifying patients at risk for advanced fibrosis but are not sufficiently accurate to replace liver biopsy.
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PMID:Diagnostic evaluation of nonalcoholic fatty liver disease. 1654 Jul 65

Non-alcoholic fatty liver disease (NAFLD) is now recognized as one of the most important causes of chronic liver disease in Western Countries, and is the hepatic manifestation of metabolic syndrome. The prevalence of NAFLD has increased with the global epidemic of obesity and type 2 diabetes mellitus. The pathophysiological hallmark of NAFLD is insulin resistance, associated with mediators of oxidative stress and inflammatory cytokines. Although simple steatosis by itself is generally benign, patients with histologically proven non-alcoholic steatohepatitis (NASH) can progress to cirrhosis. Hepatitis C (HCV) is another common cause of liver disease with some potential for progression to cirrhosis. Steatosis is present in almost 50% of patients infected by HCV. Hepatic steatosis in the setting of another liver disease (such as HCV) is associated liver disease progression. In particular, significant fibrosis is observed in patients with HCV whose liver biopsies show significant steatosis or superimposed NASH. This article reviews the host and viral factors potentially involved in the interaction between NAFLD and HCV. These factors include mediators of metabolic syndrome such as adipokines, inflammatory cytokines, factors associated with oxidative stress, lipid peroxidation products, as well as apoptosis and hepatic stellate cell activation with the resultant deposition of extracellular matrix. In addition to the mediators of metabolic syndrome (host factors), hepatic steatosis can be influenced by viral factors. The most important viral factor is HCV genotype 3, which has been independently associated with hepatic steatosis. Finally, superimposed NAFLD and visceral fat are associated with lower response rates to antiviral therapy in non-genotype 3 patients. Furthermore, viral clearance is associated with the resolution of hepatic steatosis in HCV genotype 3 but not other HCV genotypes. In these genotypes, hepatic steatosis and its impact on response to therapy are related to metabolic syndrome. Thus, the management of obesity and metabolic syndrome in patients with chronic hepatitis C may be important for reducing the risk of progression as well as improving the efficacy of antiviral therapy.
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PMID:Non-alcoholic fatty liver disease and hepatitis C infection. 1655 85

The clinical impact of nonalcoholic fatty liver disease depends on its prevalence and natural history. The prevalence in the adult population is estimated to be about 23% and is on the increase. Thus, it has become the most common cause of persistent elevated liver enzymes, chronic liver disease, and cryptogenic cirrhosis in developed countries. The increasing prevalence of nonalcoholic fatty liver disease, which is approaching epidemic proportions, is parallel to that of other disorders associated with insulin resistance, especially obesity and type 2 diabetes mellitus. This entity occurs in men and women equally and in all age groups. The natural history is poorly defined mainly due to the scarcity of histologic follow-up studies. Although steatosis alone has a more benign clinical course, steatohepatitis is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in a similar way to other causes of chronic liver diseases. Progression seems to be mainly dependent on the severity of histological damage at diagnosis, but age older than 40 years, obesity, and type 2 diabetes have also been associated with an increased risk of liver fibrosis and progression to cirrhosis.
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PMID:[Epidemiology and natural history of primary nonalcoholic fatty liver disease]. 1658 96

The newly developed elastometer, FibroScan((R)), was utilized to evaluate liver fibrosis in hepatitis C virus (HCV)- and human immunodeficiency virus (HIV)-coinfected 33 hemophiliacs and HIV-uninfected 24 patients with chronic hepatitis C. Chronicity in the liver was categorized into 4 stages by abdominal ultrasound (AUS): 1 (normal or fatty liver); 2 (chronic liver disease, mild); 3 (moderate); and 4 (severe). Stiffness of the liver was significantly increased as AUS stages advanced: 5.4+/-2.2 (N=3) versus 7.5+/-2.7 (N=9), in stage 1; 4.9+/-1.7 (N=2) versus 9.9+/-6.0 (N=10), in stage 2, 13.5+/-4.7 (N=5) versus 12.9+/-5.9 (N=6), in stage 3, and 22.0+/-9.5 (N=14) versus 28.1+/-21.3 (N=8), in stage 4, in non-HIV group and in HIV group, respectively (P=0.004 and 0.007). Stiffness was correlated with AUS stages (r=0.740, P<0.001), platelet counts (PLT; r=-0.642, P=0.001) and 7S domain of type IV collagen (IV-coll; r=0.480, P=0.024) in non-HIV group, while in HIV group, with IV-coll (r=0.801, P<0.001), AUS stages (r=-0.603, P<0.001), procollagen type III peptides (P-III-P; r=0.621, P=0.001), PLT (r=-0.480, P=0.005), and hyaluronic acid (r=0.433, P=0.027). FibroScan((R)) is absolutely noninvasive and can be the alternative to liver biopsy, especially in patients with bleeding tendency.
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PMID:Usefulness of elastometry in evaluating the extents of liver fibrosis in hemophiliacs coinfected with hepatitis C virus and human immunodeficiency virus. 1671 34


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