Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disease ranging from simple steatosis to non-alcoholic steatohepatitis, is increasingly recognized as the hepatic manifestation of metabolic syndrome and is an important cause of liver-related morbidity and mortality. It is among the most common forms of liver disease. NAFLD reflects abnormal partitioning of fat, such that fat deposition is increased in the liver, and provides a link between NAFLD and the metabolic syndrome, a constellation of metabolic disorders that can also be associated with visceral fat or central adiposity. Together, the features of the metabolic syndrome presage overt diabetes and increase cardiovascular risk. Hepatitis C virus (HCV) appears to exacerbate the metabolic syndrome by eliciting increased insulin resistance (IR) and promoting truncal obesity. Moreover, the concomitant presence of HCV and NAFLD is associated with an increased likelihood of diabetes, hypertension and/or hypertriglyceridaemia. Metabolic abnormalities have been shown to influence response to treatment such that the presence of IR or obesity reduces the likelihood of a sustained virological response (SVR); conversely, SVR has been demonstrated to ameliorate IR and improve beta-cell function. Clinically, these data suggest that attention must be paid not only to optimizing antiviral response but also to screening for and treatment of the various components of the metabolic syndrome.
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PMID:Metabolic syndrome, non-alcoholic fatty liver disease and hepatitis C virus: impact on disease progression and treatment response. 1918 68

Hepatic steatosis and liver degeneration are prominent features of the zebrafish ducttrip (dtp) mutant phenotype. Positional cloning identified a causative mutation in the gene encoding S-adenosylhomocysteine hydrolase (Ahcy). Reduced Ahcy activity in dtp mutants led to elevated levels of S-adenosylhomocysteine (SAH) and, to a lesser degree, of its metabolic precursor S-adenosylmethionine (SAM). Elevated SAH in dtp larvae was associated with mitochondrial defects and increased expression of tnfa and pparg, an ortholog of the mammalian lipogenic gene. Antisense knockdown of tnfa rescued hepatic steatosis and liver degeneration in dtp larvae, whereas the overexpression of tnfa and the hepatic phenotype were unchanged in dtp larvae reared under germ-free conditions. These data identify an essential role for tnfa in the mutant phenotype and suggest a direct link between SAH-induced methylation defects and TNF expression in human liver disorders associated with elevated TNFalpha. Although heterozygous dtp larvae had no discernible phenotype, hepatic steatosis was present in heterozygous adult dtp fish and in wild-type adult fish treated with an Ahcy inhibitor. These data argue that AHCY polymorphisms and AHCY inhibitors, which have shown promise in treating autoimmunity and other disorders, may be a risk factor for steatosis, particularly in patients with diabetes, obesity and liver disorders such as hepatitis C infection. Supporting this idea, hepatic injury and steatosis have been noted in patients with recently discovered AHCY mutations.
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PMID:TNFalpha-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafish S-adenosylhomocysteine hydrolase. 1920 49

Highly-active antiretroviral therapy (HAART) has proven remarkably effective for prolonging the life of patients with human immunodeficiency virus (HIV). However, while most HAART agents are safe, many have the potential to cause liver toxicity. Physicians must therefore consider the possibility of drug-induced liver injury in the management of HIV-infected patients, especially those with certain risk factors such as coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV), female gender, alcohol abuse, older age, or obesity. Understanding how, when, and why drug-related liver damage occurs is key to managing these patients safely and effectively. Knowledge of HAART-related liver effects will help ensure that patients receive the most benefit with the least toxicity from any given drug regimen. As more information about the mechanisms of drug related liver injury is known, clinicians will be better able to tailor therapies to suit individual situations, resulting in greater patient safety and outcomes.
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PMID:HIV-related liver disease: ARV drugs, coinfection, and other risk factors. 1921 29

Primary liver cancer, particularly hepatocellular carcinoma (HCC) remains a significant disease worldwide. It is among the top three causes of cancer death in the Asia Pacific region because of the high prevalence of its main etiological agents, chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In this region, the incidence of HCC has been static over recent decades. Older age is a major risk factor; the incidence increasing sharply after age 40 years. There is a male predilection, with male to female ratio of 3:1, except in elderly Japanese with equal sex incidence or female predominance. In most Asia-Pacific countries, chronic HBV infection accounts for 75-80% of cases; Japan, Singapore and Australia/New Zealand are exceptions because of higher prevalence of HCV infection. In spite of advances in surgery, liver transplantation and newer pharmaco/biological therapies, the survival rate has improved only slightly over recent decades, and this could be attributable to earlier diagnosis ('lead-time bias'). The majority of patients present with advanced diseases, hence reducing the chance of curative treatment. The importance of HCC may decrease in two to three decades when the prevalence of chronic HBV infection decreases as a result of the universal HBV vaccination programs implemented in late 1980s in most Asia-Pacific countries, and because of reduced incidence of medical transmission of HCV. However, transmission of HCV by injection drug use, and rising prevalence of obesity and diabetes, both independent risk factors for HCC, may partly offset this decline.
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PMID:Hepatocellular carcinoma in the Asia pacific region. 1922 Jun 70

Endogenous cannabinoids (ECs) are ubiquitous lipid signaling molecules provided by a number of central and peripheral effects, which are mediated mainly by the specific receptors CB1 and CB2. In the last decade a considerable number of studies has shown that ECs and their receptors play an important role in the pathophysiology of liver diseases. The EC system is strongly up-regulated during chronic liver diseases. Until now it has been implicated in the pathogenesis of fatty liver disease associated with obesity, alcohol abuse, and hepatitis C, in the progression of fibrosis to cirrhosis, and in the development of portal hypertension, hyperdynamic circulatory syndrome and its complications, and cirrhotic cardiomyopathy. Furthermore, the EC system can participate in the pathogenesis of acute liver injury by modulating the mechanisms responsible for cell injury and inflammatory response. Thus, targeting the CB1 and CB2 receptors represents a potential therapeutic goal for the treatment of liver diseases.
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PMID:The role of the endocannabinoid system in liver diseases. 1928 61

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and can lead to hepatocellular carcinoma and end-stage liver disease. The current FDA-approved treatment for HCV (pegylated interferon-alpha (IFNalpha) with ribavirin) is effective in only about 50% of patients. Epidemiological evidence suggests that obesity, alcohol, smoking, and environmental pollutants may contribute to resistance to IFNalpha therapy in HCV. Acrolein, a ubiquitous environmental pollutant and major component of cigarette smoke, is also generated endogenously by cellular metabolism and lipid peroxidation. This study examines the effects of acrolein on (i) IFNalpha-mediated signaling and antiviral gene expression in cultured and primary human hepatocytes and (ii) HCV replication in an HCV-replicon system. Our data demonstrate that nontoxic concentrations of acrolein significantly inhibited IFNalpha-induced tyrosine phosphorylation of both cytoplasmic and nuclear STAT1 and STAT2, without altering the total levels. Also, acrolein down-regulated IFNalpha-stimulated gene transcription, resulting in reduced expression of antiviral genes. Importantly, acrolein abolished the IFNalpha-mediated down-regulation of HCV viral expression in the HCV-replicon system. This study defines mechanisms involved in resistance to IFNalpha and identifies the pathogenic role of acrolein, and potentially other environmental pollutants, in suppressing IFNalpha antiviral activity and establishes their adverse impact on HCV therapy.
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PMID:Acrolein, a ubiquitous pollutant and lipid hydroperoxide product, inhibits antiviral activity of interferon-alpha: relevance to hepatitis C. 1934 60

We evaluated the prevalence and the risk factors for gallstone disease in patients with chronic hepatitis C infection. We investigated 453 consecutively admitted patients with chronic infection with hepatitis C virus (HCV) (cirrhosis excluded) and 879 patients without liver disease (October 2006-April 2007). Gallstone disease was diagnosed if gallstones were present at ultrasonography or if there had been a previous cholecystectomy. Variables evaluated were age, gender, gallstone heredity, body mass index, waist circumference, parity, serum lipids, fatty liver, arterial hypertension, diabetes mellitus and metabolic syndrome (International Diabetes Federation criteria). Informed consent was obtained from all patients. We found that 88 of 453 (19%) patients with chronic HCV hepatitis (age 50.1 +/- 11.7 years) and 153 of 879 (17%) controls (age 60.6 +/- 12.6 years) had gallstone disease (GD). Abdominal obesity (OR = 2.108, 95% CI 1.287-3.452) and steatosis (OR = 3.699, 95% CI 2.277-6.008) were risk factors for GD in HCV patients. Gallstone heredity, dyslipidaemia, type 2 diabetes mellitus and metabolic syndrome increased the risk for GD in controls vs HCV patients. Our study shows that even HCV patients with chronic hepatitis but not cirrhosis have an increased prevalence of gallstones. Compared with controls, gallstones are present in HCV patients at a younger age and are associated with central obesity and liver steatosis, but not with gallstone heredity, dyslipidaemia, diabetes mellitus or metabolic syndrome. Although we could not establish a temporal relationship, the association between HCV infection and gall stone disease is real and appears to be causally linked, at least in predisposed individuals (obese and with liver steatosis).
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PMID:Hepatitis C virus infection is a risk factor for gallstone disease: a prospective hospital-based study of patients with chronic viral C hepatitis. 1948 79

Adipokines are polypeptides secreted in the adipose tissue in a regulated manner. While some of these molecules are expressed only by adipocytes, resident and infiltrating macrophages and components of the vascular stroma markedly contribute to expression of other adipokines. As a result, adipose tissue inflammation is associated with a modification in the pattern of adipokine secretion. Leptin, adiponectin, and resistin are the best-studied molecules in this class, but cytokines such as tumor necrosis factor or interleukin-6 are also secreted at high levels by the adipose tissue. Several other molecules have been recently identified and are actively investigated. Adipokines interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Several studies have investigated plasma levels of adiponectin in patients with nonalcoholic fatty liver disease, to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. Hepatitis C is another disease where adipokines may represent a link between viral infection, steatosis, and metabolic disturbances. Identification of the mediators secreted by expanded adipose tissue and their pathogenic role is pivotal in consideration of the alarming increase in the prevalence of obesity and of the detrimental role that this condition exerts on the course of liver diseases.
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PMID:Adipokines in liver diseases. 1958 55

Although chronic infection with hepatitis B virus and/or hepatitis C virus are the most important risk factors for hepatocellular carcinoma (HCC) worldwide, other causes of cirrhosis can also lead to HCC. Given the high prevalence of alcoholism and the worldwide obesity epidemic, the relevant importance of nonviral liver disease-related HCC is expected to increase in the future. Some evidence supports mechanistic interactions between host or environmental factors and chronic viral hepatitis in the development of HCC. For example, food- and water-borne carcinogens have contributed to unusually high rates of HCC in parts of China and sub-Saharan Africa. With some of these conditions, appropriate public health measures to reduce the population's exposure to known etiologic agents, or early therapeutic intervention for 'at-risk' individuals before development of cirrhosis (e.g. hereditary hemochromatosis) can prevent HCC. Community-based programs to discourage and deal with excessive alcohol intake, to promote tobacco smoking awareness, to avoid exposure to aflatoxin and other food toxins, and measures to reduce the pandemic of obesity and diabetes are vital for effective interruption of the rising tide of HCC from nonviral liver disease.
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PMID:Prevention of hepatocellular carcinoma in nonviral-related liver diseases. 1964 14

Non-invasive modalities to estimate fibrosis stage are desirable in hepatitis C-infected haemophilia patients. Previous studies found a high rate of significant fibrosis both by Fibrotest (FT) and Fibroscan (FS) in these patients. To estimate liver fibrosis and to assess the concordance between FT and FS in hepatitis C-infected haemophilia patients. FT and FS were performed at different laboratories and were unaware of the results of the alternative test. Three successive liver stiffness measurements (LSM) were performed at different sites on the liver. Two-validated algorithms were used to improve evaluation of fibrosis by non-invasive methods. Fifty-seven hepatitis C-infected haemophilia patients were evaluated by FT and FS. Acquisition of LSMs was not feasible in two patients: obesity--one, surgical scars--one. Fibrosis stage > or=F2, > or =F3 or =F4 were estimated in about a half, about a third and in 15-20% of the evaluated patients by FS and FT respectively. The corresponding concordance rates and kappa score for fibrosis stage > or =F2, > or =F3 or =F4 between FT and FS were 62%, 69%, 85% and 0.24, 0.32, 0.44 respectively. Using the two aforementioned algorithms, additional 14 patients could be reliably estimated for fibrosis stage > or =F2. High proportion hepatitis C-infected haemophilia patients were estimated with significant or advanced stages of liver fibrosis using both tests. Nevertheless, the agreement between modalities was only fair and improved with more advanced stages of fibrosis. Practical algorithms for the accuracy of FT and FS may improve reliable evaluation of fibrosis in this population.
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PMID:Fibrotest or Fibroscan for evaluation of liver fibrosis in haemophilia patients infected with hepatitis C. 1970 31


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