Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcoholic fatty liver disease, an entity that includes nonalcoholic steatohepatitis, is typically a benign, indolent condition. However, in a subset of patients, the clinical course may progress to advanced cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Unfortunately, the pathogenesis, natural history, and potential therapies for these disorders remain poorly understood. Identifying patients who should be targeted for potential treatment remains difficult. Liver biopsy should be considered to assess the degree of hepatic inflammation and fibrosis, because physical examination findings, biochemical parameters, and the results of radiographic studies have been shown to correlate poorly with the severity of steatohepatitis and fibrosis. Although there is some evidence suggesting that obesity, diabetes mellitus, older age, and perhaps an aspartate transaminase:alanine aminotransaminase ratio higher than 1 may be predictors of more advanced fibrosis, histology remains the gold standard. Most patients with simple hepatic steatosis appear to follow a benign course and probably do not require aggressive therapy. Conversely, patients with steatohepatitis with extensive inflammation and fibrosis are the patients who are most likely to benefit from effective therapies. The most commonly recommended treatment is weight loss. Existing data suggest that rapid weight loss may promote hepatic inflammation and fibrosis; therefore, gradual weight loss should be recommended. Large, randomized, controlled trials evaluating the long-term histologic impact and clinical outcomes of weight loss strategies are lacking. Potentially promising pharmacologic therapies include insulin-sensitizing oral hypoglycemic agents such as metformin and the thiazolidenediols, antihyperlipidemic agents such as gemfibrozil or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, vitamin E and other antioxidants, ursodeoxycholic acid, and betaine. As with weight loss, data regarding the efficacy of these pharmacologic options are limited. In addition, there are no widely accepted guidelines to help direct the clinician in the optimal use of these agents in patients with nonalcoholic fatty liver diseases.
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PMID:Therapeutic Options in Nonalcoholic Fatty Liver Disease. 1240 79

Non-alcoholic fatty liver disease is a new clinicopathological condition of emerging importance, now recognized as the most common cause of abnormal liver tests. It is characterized by a wide spectrum of liver damage: simple steatosis may progress to advanced fibrosis and to cryptogenic cirrhosis through steatohepatitis, and ultimately to hepatocellular carcinoma. Obesity is the most significant single risk factor for the development of fatty liver, both in children and in adults; obesity is also predictive of the presence of fibrosis, potentially progressing to advanced liver disease. From a pathogenic point of view, insulin resistance plays a central role in the accumulation of triglycerides within the hepatocytes and in the initiation of the inflammatory cascade. Chronic hepatocellular injury, necroinflammation, stellate cell activation, progressive fibrosis and ultimately, cirrhosis may be initiated by peroxidation of hepatic lipids and injury-related cytokine release. In the last few years, several pilot studies have shown that treatment with insulin-sensitizing agents, anti-oxidants or cytoprotective drugs may be useful, but there is no evidence-based support from randomized clinical trials. Modifications in lifestyle (e.g. diet and exercise) to reduce obesity remain the mainstay of prevention and treatment of a disease, which puts a large number of individuals at risk of advanced liver disease in the near future.
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PMID:Hepatic steatosis in obese patients: clinical aspects and prognostic significance. 1496 5

Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis have a risk of development of hepatocellular carcinoma. Peroxisome proliferator-activated receptor (PPAR) gamma ligand has recently been reported to have improved the condition of patients with NASH. The aim of this study was to investigate whether pioglitazone, a PPARgamma ligand, has any influence on the animal model of NASH as well as isolated hepatic stellate cells. In vivo, the effects of pioglitazone were examined using the choline-deficient L-amino acid-defined (CDAA)-diet liver fibrosis model. After two weeks, pioglitazone improved hepatic steatosis, prevented liver fibrosis, and reduced preneoplastic lesions in the liver after 10 weeks. Pioglitazone reduced the expression of TIMP-1 and TIMP-2 mRNA without changing MMP-13 mRNA expression compared to the liver fed a CDAA diet alone. In vitro, pioglitazone prevented the activation of hepatic stellate cells resulting in reducing the expression of type I procollagen, MMP-2, TIMP-1, and TIMP-2 mRNA with increased MMP-13 mRNA expression. These results indicate that pioglitazone may be one of the candidates for the benefit drugs for the liver disease of patients with NASH.
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PMID:Pioglitazone prevents hepatic steatosis, fibrosis, and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet. 1501 44

Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as a common liver disorder that represents the hepatic manifestation of the metabolic syndrome, a variably defined aggregate of disorders related to obesity, insulin resistance, type II diabetes, hypertension and hyperlipidemia. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury that carries a risk for progressive fibrosis, cirrhosis, and end-stage liver disease. Hepatocellular carcinoma (HCC) is a documented complication in an as yet unknown percentage of cases of NASH cirrhosis. The diagnosis of nonalcoholic steatohepatitis requires histopathologic evaluation because the lesions of parenchymal injury and fibrosis cannot be detected by imaging studies or laboratory tests. This article will briefly discuss prevalence studies and the pathophysiology of NAFLD and focus on current discussions related to the specific lesions in the pathology of NASH, including the challenges of pediatric NASH and NASH-related cirrhosis.
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PMID:Nonalcoholic steatohepatitis. 1508 83

Liver biopsy is traditionally the 'gold standard' for the evaluation of liver diseases. There are several situations in which its role is being challenged. In hepatitis C, liver biopsy helps assess prognosis and treatment candidacy. An important exception is genotype 2 or 3 because treatment is more likely to succeed and therapy is relatively short in duration. For hepatitis B, liver biopsy gives some prognostic information, but serologic tests and hepatic biochemical tests are the primary determinants of treatment candidacy. Non-alcoholic fatty liver disease can be accurately diagnosed without a liver biopsy and, furthermore, there are no specific therapies available. The role of liver biopsy to assess methotrexate-associated hepatotoxicity remains controversial. Finally, patients with focal liver lesions usually do not require biopsy and, in the case of hepatocellular carcinoma, biopsy carries a risk of needle-track seeding. In short, the need for liver biopsy depends on the specific situation and should be performed when there is sufficient uncertainty about diagnosis, severity of disease, prognosis, and treatment decisions.
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PMID:Review article: the evolving role of liver biopsy. 1527 61

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease in the United States. The histologic spectrum of NAFLD ranges from steatosis liver alone to nonalcoholic steatohepatitis (NASH), which is the most serious form of NAFLD. NASH is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in up to 20% and 12%, respectively, over a 10-year period. NASH-associated cirrhosis also can develop into subacute liver failure, progress to hepatocellular carcinoma, and reoccur post-transplantation. In contrast, steatosis alone has a more benign clinical course, although progression to cirrhosis has occurred in 3% of these patients. The major risk factors for fibrosis include diabetes or obesity, an aspartate aminotransferase/alanine aminotransferase ratio of greater than 1, age older than 50, and hepatic histology.
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PMID:The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. 1533 Oct 61

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disorder occurring in individuals without significant alcohol consumption. It consists of a spectrum of liver disease, ranging from simple steatosis to steatohepatitis, cirrhosis, liver failure, and hepatocellular carcinoma. Although a number of conditions have been identified as risk factors, obesity is by far the most dominant risk factor for developing NAFLD. Over the past decade, it became apparent that NAFLD in some patients is a progressive disorder,leading to cirrhosis and liver failure. Despite lack of direct evidence,due to the ongoing epidemic of obesity in western countries, it is believed that the incidence of NAFLD is increasing, and patients with complicated and uncomplicated NAFLD will present in increasing numbers to primary care physicians as well as specialists. This article discusses the prevalence, histologic spectrum, and natural history of NAFLD in subjects with severe obesity as well as the hepatic effects of drastic weight loss induced by bariatric surgery or severe calorie restriction.
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PMID:Nonalcoholic fatty liver disease in individuals with severe obesity. 1533 Oct 62

Nonalcoholic fatty liver (NAFL) is associated with fundamental issues of fat metabolism and insulin resistance. These abnormalities have been linked to impairment of ATP homeostasis, and a growing body of literature has reported mitochondrial abnormalities in various forms of hepatic steatosis. The changes are evident as structural abnormalities, including greatly increased size and the development of crystalline inclusions, and are usually regarded as pathologic, reflecting either a protective or degenerative response to injury. Although the relationships between structural changes,decreased mitochondrial function, and disease states are becoming clearer, the molecular basis for the perturbations is not well understood. Oxidative damage is the most likely causative process and may result in alterations of mitochondrial DNA (mtDNA), stimulated apoptotic pathways, and increased propensity for necrosis.Overall mitochondrial health likely depends on multiple factors including the integrity of the mtDNA, the composition of cellular lipids, lipoprotein trafficking, the balance of pro- and antioxidant factors, and the metabolic demands placed on the liver. Mitochondrial dysfunction may play a role in numerous clinical conditions associated with NAFL, such as hepatocellular carcinoma, lipodystrophy,age-related insulin resistance, gut dysmotility, cryptogenic cirrhosis, a mild form of gaze palsy, and possibly other more severe neurodegenerative diseases. The prominent role of mitochondrial dysfunction in NAFL provides a new and exciting paradigm in which to view this disorder, its complications, and potential dietary and pharmacologic intervention.
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PMID:Mitochondria in nonalcoholic fatty liver disease. 1533 Oct 66

Non-alcoholic fatty liver disease (NAFLD) is a common clinical condition which is fast assuming importance as a possible precursor of more serious liver disorders, including cirrhosis of the liver and hepatocellular carcinoma. There are no data in the published English literature on the prevalence of NAFLD in India. The present study was performed to assess a prevalence of NAFLD by ultrasonography in a general population in coastal eastern India. Asymptomatic, apparently healthy attendants accompanying the patients attending the Gastroenterology outpatient were subjected to abdominal ultrasonographic examination for the presence of fatty liver; individuals who gave a history of alcohol abuse were excluded from the study. The subjects of the study comprised 159 apparently healthy attendants, who underwent ultrasonography. Fatty liver was diagnosed by ultrasonography in 39 of these 159 persons (24.5%). Fatty liver was seen more commonly in males (26.9%) than in females (13.8%). Persons with ultrasonographic fatty liver had a higher body mass index (BMI) (mean 25.9 +/- 4.17 kg/m2) than persons without fatty liver (mean 22.1 +/- 3.27 kg/m2) (p<0.001). The estimated prevalence of NAFLD in an unselected apparently healthy and asymptomatic population as detected by ultrasonography in our study was found to be 24.5%. This is similar to the prevalence rate published from the west. However, contrary to figures from the west, males appeared to have a greater predilection for fatty liver than females in our study. NAFLD is perhaps as common in developing world as in the developed countries despite a lower prevalence of obesity. Indian males may have a greater genetic predisposition to developing NAFLD.
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PMID:Prevalence of nonalcoholic fatty liver disease in coastal eastern India: a preliminary ultrasonographic survey. 1547 21

Non-alcoholic steatohepatitis (NASH) is an underdiagnosed liver disease characterized by steatosis, necroinflammation and fibrosis. This disease may eventually develop into cirrhosis and hepatocellular carcinoma. NASH is highly prevalent among obese individuals and among patients with diabetes mellitus type 2. Non-alcoholic fatty liver (NAFL), a precursor of NASH, is the main cause of elevated serum liver enzymes among the general population. In NASH the liver is programmed to lipogenesis rather than to glycogenesis and herein insulin-resistance plays a major role. Gradual weight loss, physical exercise and drugs that improve insulin sensitivity are potential therapies.
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PMID:Non-alcoholic steatohepatitis. 1548 64


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