Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic steatosis is a consequence of both obesity and ethanol use. Nonalcoholic steatosis (NASH) resemble alcoholic steatosis and steatohepatitis. Both exhibit increased hepatocellular triglycerides(TG), reflecting an increase in long chain fatty acids (LCFA). LCFA enter cells by both facilitated transport and passive diffusion. A driving force for both is the plasma unbound LCFA concentration ([LCFAu]). In both obese rodents and obese patients, adipocyte LCFA uptake via both facilitated transport and diffusion is increased. However, the LCFA uptake Vmax in hepatocytes is not increased in obese animals. Nevertheless, total LCFA uptake in obese rodents is increased ~3-fold, reflecting increased plasma LCFA concentrations. With advancing obesity, resistance to the antilipolytic effects of insulin results in increased lipolysis within the omental fat depot, a consequent further rise in portal venous LCFA, and an even greater rise in portal [LCFAu]. This causes a further increase in hepatocellular LCFA uptake, increased intracellular generation of reactive oxygen species (ROS), and transition from simple steatosis to NASH. By contrast, in rodent hepatocytes and in human hepatoma cell lines, ethanol up-regulates the LCFA uptake Vmax. Consequently, although plasma LCFA are unaltered, hepatocellular LCFA uptake in ethanol-fed rats is also increased~3-fold, leading to increased ROS generation and evolution of alcoholic hepatitis. Thus, while increased hepatic LCFA uptake contributes to the pathogenesis of both NASH and alcoholic hepatitis,the underlying mechanisms differ. Recognizing these mechanistic differences is important in developing strategies for both prevention and treatment of these conditions.
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PMID:Lipid metabolism in hepatic steatosis. 1533 Oct 68

Statins are drugs widely used in humans to treat hypercholesterolemia. Statins act by inhibiting cholesterol synthesis resulting in the activation of the transcription factor sterol-responsive element-binding protein-2 that controls the expression of genes involved in cholesterol homeostasis. Statin therapy also decreases plasma triglyceride and non-esterified fatty acid levels, but the mechanism behind this effect remains more elusive. Liver fatty acid-binding protein (L-FABP) plays a role in the influx of long-chain fatty acids into hepatocytes. Here we show that L-FABP is a target for statins. In rat hepatocytes, simvastatin treatment induced L-FABP mRNA levels in a dose-dependent manner. Moreover, L-FABP promoter activity was induced by statin treatment. Progressive 5'-deletion analysis revealed that the peroxisome proliferator-activated receptor (PPAR)-responsive element located at position -67/-55 was responsible for the statin-mediated transactivation of the rat L-FABP promoter. Moreover, treatment with simvastatin and the PPARalpha agonist Wy14,649 resulted in a synergistic induction of L-FABP expression (mRNA and protein) in rat Fao hepatoma cells. This effect was also observed in vivo in wild-type mice but not in PPARalpha-null animals demonstrating the direct implication of PPARalpha in L-FABP regulation by statin treatment. Statin treatment resulted in a rise in PPARalpha mRNA levels both in vitro and in vivo and activated the mouse PPARalpha promoter in a reporter assay. Altogether, these data demonstrate that L-FABP expression is up-regulated by statins through a mechanism involving PPARalpha. Moreover, PPARalpha might be a statin target gene. These effects might contribute to the triglyceride/non-esterified fatty acid-lowering properties of statins.
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PMID:Statin induction of liver fatty acid-binding protein (L-FABP) gene expression is peroxisome proliferator-activated receptor-alpha-dependent. 1533 40

Alcohol abuse and hepatitis C virus (HCV) infection coexist with chronic liver disease in many patients. The mechanism of injury in these patients is probably multifactorial and involves, but is not limited to, a combination of diminished immune clearance of HCV, oxidative stress, emergence of HCV quasi-species, hepatic steatosis, increased iron stores, and increased rate of hepatocyte apoptosis. In patients with HCV infection, alcohol consumption is known to cause accelerated progression of liver fibrosis, higher frequency of cirrhosis, and increased incidence of hepatocellular carcinoma (HCC). These patients also have decreased survival as compared with patients with either alcohol abuse or HCV liver injury alone. Alcohol abuse causes decreased response to interferon treatment in HCV patients. It is therefore necessary for patients with HCV infection to abstain from alcohol consumption.
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PMID:Alcohol and hepatitis C. 1534 7

The metabolic syndrome is one of the most common disease of our era that may cause numerous complications. There are some studies showing the need to take attention to the hepatic manifestation of the metabolic syndrome besides its already well-known consequences. In most of the cases there are histopathological evidences for the presence of fatty liver and mainly non alcoholic steatohepatitis. These conditions can lead to hepatic cirrhosis, hepatic failure or even to hepatocellular carcinoma. The risk of these consequences is the greater the more severe the metabolic syndrome is and the more components of it are included. All these emphasise the importance of examining the hepathological status of the patients suffering from the metabolic syndrome.
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PMID:[Is non alcoholic steatohepatitis (NASH) part of the metabolic syndrome?]. 1545 20

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

Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most important risk factors for the development of hepatocellular carcinoma (HCC) in humans. HBV is the primary cause of HCC in high-risk areas including China and Africa, whereas in developed countries such as the United States, HCV plays a more prominent role and is at least partially responsible for the increase in HCC incidence in this country. Humans are exposed to hepatocarcinogenic aflatoxins through ingestion of moldy foods, a consequence of poor storage of susceptible grains. Highly exposed populations are primarily in sub-Sahara Africa and Asia, where dietary aflatoxins significantly enhance the carcinogenic effects of viral hepatitis. Heavy, long-term alcohol use is a risk factor for HCC, whereas moderate use (1-3 drinks/day) is not. Constituents of cigarette smoke are hepatic carcinogens in animals, and there is mounting evidence that the liver is an organ susceptible to tobacco carcinogenicity. Diabetic patients are at risk for HCC probably as a result of the hepatic injury, fibrosis, and eventual cirrhosis resulting from fatty liver disease. Given the current epidemic of obesity and diabetes in the United States, this risk factor will be increasingly important. Increased risk for HCC is evident in young noncirrhotic users of oral contraceptives in the United States and Europe. In summary, risk factors for HCC are identifiable in most patients and primarily are associated with chronic hepatic injury.
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PMID:Environmental factors and risk for hepatocellular carcinoma. 1550 6

Epidemiological studies have shown that obesity is a risk factor for hepatocellular carcinoma. Similar studies further indicate that diabetes is also a major risk factor. Both obesity and diabetes are frequently associated with nonalcoholic fatty liver disease, and case reports have shown progression of nonalcoholic fatty liver disease to cirrhosis and hepatocellular carcinoma. Although no study has clearly tied all of these variables together, it is likely that the association of hepatocellular carcinoma with obesity represents the progression of underlying nonalcoholic fatty liver disease to cirrhosis. The mechanism most likely involves replicative senescence of steatotic mature hepatocytes and compensatory hyperplasia of progenitor (oval) cells as a reaction to chronic injury due to ongoing nonalcoholic steatohepatitis and resultant hepatic fibrosis. Growth factors associated with chronic inflammation, type 2 diabetes, and DNA mutations as a result of lipid peroxidation probably play significant roles in clonal expansion and hepatocellular carcinoma progression. It remains unclear whether cirrhosis is a prerequisite for the development of hepatocellular carcinoma or whether hepatocellular carcinoma can develop in fatty liver in the absence of cirrhosis. However, well-documented case reports suggest that most cases of hepatocellular carcinoma arise in the setting of nonalcoholic steatohepatitis with cirrhosis. Whether therapy aimed at nonalcoholic fatty liver disease reduces the risk of hepatocellular carcinoma remains to be shown. Prophylactic measures and the role of cancer surveillance have not been adequately investigated, but current evidence suggests a risk for hepatocellular carcinoma in nonalcoholic steatohepatitis-related cirrhosis that rivals that of hepatocellular carcinoma in hepatitis C virus-related cirrhosis, particularly in older male patients.
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PMID:Obesity and hepatocellular carcinoma. 1550 9

Persistent infection of hepatitis C virus (HCV) can lead to a high risk for hepatocellular carcinoma(HCC). HCV core protein plays important roles in HCV-induced hepatocarcinogenesis, because its expression in mice causes hepatic steatosis and HCC without accompanying hepatitis. However, its precise mechanisms remain unclear. We investigated whether the HCV core protein alters the expression of the factors associated with hepatic steatosis and HCC in vivo. By Western immunoblot and Northern blot analyses, expression of the proteins including fatty acid-metabolizing enzymes and cell cycle regulators, which are induced by the activation of peroxisome proliferator-activated receptor alpha (PPARalpha), significantly increased in HCV core protein transgenic mice. This result suggests the possibility that PPARalpha activation might contribute to HCV core protein-mediated hepatocarcinogenesis.
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PMID:[Possible mechanisms of hepatitis C virus-related hepatocarcinogenesis]. 1555

Non-alcoholic fatty liver disease (NAFLD) is a frequent syndrome encompassing fatty liver alone and steatohepatitis (NASH). Often asymptomatic, the suspicion arises because of abnormal aminotransferases or a bright liver on abdominal ultrasound. It should be suspected during evaluation of associated conditions as obesity, diabetes or dyslipidaemia. The diagnostic evaluation must exclude other potential causes of liver disease and may include a liver biopsy, the only method able to confirm features of necroinflammation and fibrosis that define NASH and its prognostic implications. Indeed, the presence of necroinflammation has been associated with a significant risk of progression to cirrhosis and eventually hepatocellular carcinoma. Age >45 years, obesity and diabetes have also been associated with an increased risk of liver fibrosis and progression to cirrhosis. Given the high prevalence of NAFLD, general measures of life-style changes, focusing on exercise, diet, and total alcohol abstinence, should be implemented before a liver biopsy is considered.
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PMID:Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): diagnosis and clinical course. 1556 40

Obesity-related liver disease, particularly nonalcoholic fatty liver disease and its more severe form nonalcoholic steatohepatitis, is being increasingly recognized as a common liver disease in developed countries and represents hepatic manifestation of the metabolic syndrome. Nonalcoholic steatohepatitis results in progressive fibrosis, cirrhosis, and end-stage liver disease, with its increased incidence of hepatocellular carcinoma. Liver biopsy remains the gold standard in detection, evaluation, staging, and grading of nonalcoholic steatohepatitis. Liver biopsy also provides an important tool to detect concomitant liver disease that may accelerate the progression of steatohepatitis in these patients. Surgical or drug-induced weight loss has been documented to reduce the amount of inflammation, to induce regression of fibrosis, and, in some cases, to cause a reversal of cirrhosis in obese patients with steatohepatitis. Pretreatment or intraoperative liver biopsy should be performed to assess the presence of steatohepatitis, and stage and grade of steatohepatitis. This article will discuss obesity-related liver diseases, focusing on pathologic features in liver biopsies from obese patients, obesity-related hepatocellular carcinoma, and the effect of weight loss treatment on histopathology.
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PMID:Liver pathology in obesity. 1560 4


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