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

Hepatocellular cancer is the fifth most frequent cancer in men and the eighth in women worldwide. Established risk factors are chronic hepatitis B and C infection, chronic heavy alcohol consumption, obesity and type 2 diabetes, tobacco use, use of oral contraceptives, and aflatoxin-contaminated food. Almost 90% of all hepatocellular carcinomas develop in cirrhotic livers. In Western countries, attributable risks are highest for cirrhosis due to chronic alcohol abuse and viral hepatitis B and C infection. Among those with alcoholic cirrhosis, the annual incidence of hepatocellular cancer is 1-2%. An important mechanism implicated in alcohol-related hepatocarcinogenesis is oxidative stress from alcohol metabolism, inflammation, and increased iron storage. Ethanol-induced cytochrome P-450 2E1 produces various reactive oxygen species, leading to the formation of lipid peroxides such as 4-hydroxy-nonenal. Furthermore, alcohol impairs the antioxidant defense system, resulting in mitochondrial damage and apoptosis. Chronic alcohol exposure elicits hepatocyte hyperregeneration due to the activation of survival factors and interference with retinoid metabolism. Direct DNA damage results from acetaldehyde, which can bind to DNA, inhibit DNA repair systems, and lead to the formation of carcinogenic exocyclic DNA etheno adducts. Finally, chronic alcohol abuse interferes with methyl group transfer and may thereby alter gene expression.
 ...
PMID:Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. 1660 31

Hepatic steatosis (including microvesicular and macrovesicular fat) is a significant histologic feature associated to the chronic hepatitis C (HCV). The purpose of this paper was to analyze the incidence of hepatocyte steatosis in patients with HCV and the potential role of some the known variables as risk factors possibly involved in the occurrence of steatosis: age, sex, obesity, biological parameters, diabetes mellitus, degree of necroinflammation (NI) and stage of fibrosis. 96 of 125 (76.8%) patients had hepatic steatosis (mild 76%, moderate and severe 24%); in comparison with patients without steatosis, those with HCV and steatosis were more frequently women (males/females: 1/1.9) of older age (49.97 vs. 47.7 years), with a greater ICM (index of corporal mass) (26.55 sqm vs. 23.52 sqm), with raised glycemic values (13 of the 14 patients with HCV and diabetes mellitus had steatosis), an average value of serum ALT significantly raised (95.38 U/l vs. 78.96 U/l), and an average score of NI activity significantly higher (9.39 vs. 6.75).
 ...
PMID:Hepatic steatosis associated with hepatitis C virus infection. 1668 64

Obesity and the metabolic syndrome have hepatic manifestations, including steatosis and progression of fibrosis. In individuals with chronic hepatitis C, obesity is associated with inflammation, insulin resistance, steatosis, progression of fibrosis, and nonresponse to treatment with interferon or peginterferon alpha and ribavirin. Patients with both hepatitis C and obesity-related nonalcoholic fatty liver disease are at greater risk for more advanced liver disease. We review the mechanisms by which obesity may be associated with decreased efficacy of interferon-based therapies in individuals with chronic hepatitis C and the therapeutic strategies that may increase the effectiveness of these therapies in obese individuals.
 ...
PMID:Impact of obesity on treatment of chronic hepatitis C. 1672 27

Several hormones that regulate nutritional status also impact on bone metabolism. Preptin is a recently isolated 34-amino acid peptide hormone that is cosecreted with insulin and amylin from the pancreatic beta-cells. Preptin corresponds to Asp(69)-Leu(102) of pro-IGF-II. Increased circulating levels of a pro-IGF-II peptide complexed with IGF-binding protein-2 have been implicated in the high bone mass phenotype observed in patients with chronic hepatitis C infection. We have assessed preptin's activities on bone. Preptin dose-dependently stimulated the proliferation (cell number and DNA synthesis) of primary fetal rat osteoblasts and osteoblast-like cell lines at periphysiological concentrations (>10(-11) M). In addition, thymidine incorporation was stimulated in murine neonatal calvarial organ culture, likely reflecting the proliferation of cells from the osteoblast lineage. Preptin did not affect bone resorption in this model. Preptin induced phosphorylation of p42/p44 MAP kinases in osteoblastic cells in a dose-dependent manner (10(-8)-10(-10) M), and its proliferative effects on primary osteoblasts were blocked by MAP kinase kinase inhibitors. Preptin also reduced osteoblast apoptosis induced by serum deprivation, reducing the number of apoptotic cells by >20%. In vivo administration of preptin increased bone area and mineralizing surface in adult mice. These data demonstrate that preptin, which is cosecreted from the pancreatic beta-cell with amylin and insulin, is anabolic to bone and may contribute to the preservation of bone mass observed in hyperinsulinemic states such as obesity.
 ...
PMID:Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo. 1691 56

Hepatitis C virus (HCV) is one of the most important causes of chronic hepatitis globally, and particularly in Egypt. Abnormal blood counts have been noted in clinics among patients with HCV infection. The present work is a case control study conducted in Damanhour Medical National Institute (DMNI) to evaluate the frequency and severity of peripheral blood cell abnormalities in HCV- infected Egyptian patients. Two groups of individuals were randomly selected, group 1 comprised 100 patients suffering from chronic active hepatitis C with positive RNA PCR, and group 2 comprised 100 healthy persons and represented the control group. Low neutrophil and platelet counts, but not anemia were noticed in the first group and were significantly different when compared to the control group (<2.1x10(9)/L in 27% of patients versus 10% of controls and <175x10(9)/L in patients versus 11% of controls respectively at p<0.01). Obesity, advanced age and anti HCV seropositivity were independently associated with neutropenia, while advanced age and female gender and anti HCV seropositivity were associated with thrombocytopenia among HCV infected patients.
 ...
PMID:Blood count profile in chronic active hepatitis (C) Egyptian patients. 1691 51

Insulin resistance is more often seen in hepatitis C than in other liver diseases, including non-alcoholic steatohepatitis. The Homeostasis Model for Assessment [HOMA= fasting insulin (mUI/ml) * fasting glucose (mmol/L) / 22.5] has proved useful in the measurement of insulin sensitivity in euglycemic patients. Cross-sectional and case-cohort studies support a role for hepatitis C as a factor implied in the development of type-2 diabetes in high-risk patients (male patients, older than 40 years, and overweight). In transgenic mice models the HCV core protein has been found to induce insulin resistance via TNF production. Insulin resistance has been associated with steatosis development and fibrosis progression in a genotype-dependent manner. In genotype-1 patients, the mechanisms by which insulin resistance promotes fibrosis progression include: a) steatosis; b) hyperleptinemia; c) increased TNF production; and d) impaired expression of PPARg receptors. Indeed, insulin resistance has been found as a common denominator to the majority of features associated with difficult-to-treat patients. Patients with cirrhosis, obesity, coinfected with HIV, and Afro-American, all of them showed insulin resistance. Insulin resistance strongly influences sustained response rates, at least in genotype-1 patients. Insulin resistance decreases during and after treatment in patients that achieved virus C clearance. Moreover, the incidence of type-2 diabetes seems to be lower in responders than in non-responders. In summary, hepatitis C promotes insulin resistance and insulin resistance induces steatosis, fibrosis, and interferon resistance. The treatment of insulin resistance by decreasing hyperinsulinemia could improve sustained response rates in patients with chronic hepatitis C treated with peginterferon plus ribavirin.
 ...
PMID:Hepatitis C and insulin resistance: steatosis, fibrosis and non-response. 1704 97

Studies have indicated a high prevalence of hepatic steatosis in patients with chronic hepatitis C (CHC). To address the impact of steatosis on the clinical course of CHC and treatment response requires large multicenter studies. The present study analyzed hepatitis C virus (HCV)-infected veterans enrolled in a U.S. Veteran Administration multicenter study of the epidemiology and response to interferon alpha-2b and ribavirin treatment. Of the 357 patients, 97.1% were males, with a mean age of 48.7+/-6.4 years, and 184 (51.5%) had hepatic steatosis. The mean body mass index (BMI) was 29.3+/-5.2 kg/m(2), including 37.1% who were obese (BMI, > or =30 kg/m(2)). Stage III-IV fibrosis was present in 111 of 334 (33.3%) of the patients. After adjusting for age, race, and history of alcohol use in the past 12 months, only stage III-IV fibrosis was independently and significantly associated with hepatic steatosis (P=0.03). There was a trend of association between obesity and steatosis independent of the other factors. Only HCV genotype was independently associated with a sustained virological response (SVR) to interferon alpha-2b and ribavirin treatment after adjusting for age, alcohol use, steatosis, BMI, stage III-IV fibrosis, serum AFP, and HCV load. In conclusion, analyses of our multicenter trial data demonstrated that the prevalence of hepatic steatosis is 51.5% in HCV-infected U.S. veterans. We found that steatosis is independently associated with stage III-IV fibrosis. However, only HCV genotype, and not steatosis, obesity, or stage III-IV fibrosis, was associated with SVR to interferon alpha-2b and ribavirin treatment.
 ...
PMID:Clinical implications of hepatic steatosis in patients with chronic hepatitis C: a multicenter study of U.S. veterans. 1722 72

As obesity prevalence rises, there is evidence that fatty liver disease can act synergistically with other chronic liver diseases to aggravate parenchymal injury. This is characterized best in chronic hepatitis C, where steatosis is caused by viral and metabolic effects. There is evidence that steatosis and its metabolic abnormalities also exacerbate other diseases, such as alcoholic liver disease, hemochromatosis, and, possibly, drug-induced liver disease. The pathogenesis seems related to increased susceptibility of steatotic hepatocytes to apoptosis, enhanced oxidative injury, and altered hepatocytic regeneration. Data suggest that active management of obesity may improve liver injury and decrease the progression of fibrosis in patients who have other chronic liver diseases.
 ...
PMID:Steatosis as a cofactor in other liver diseases: hepatitis C virus, alcohol, hemochromatosis, and others. 1754 78

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide, and one of the fastest rising tumors as a result of chronic hepatitis B and C infection. The patients at risk for developing HCC are those with underlying cirrhosis secondary to viral hepatitis. External factors such as alcohol, tobacco, obesity, and diabetes increase the risk of HCC among those with chronic viral hepatitis. Surveillance of patients with cirrhosis with alpha-fetoprotein and ultrasound has been shown to reduce survival. The diagnosis of HCC is established by the presence of an arterially enhancing mass in the presence of cirrhosis. Viral hepatitis represents an opportunity for prevention of HCC.
 ...
PMID:Viral hepatitis and hepatocellular carcinoma. 1761 52

Hepatitis C infection and non-alcohol-related hepatic steatosis are the most common liver diseases worldwide, and both conditions often co-exist in the same patient. Hepatitis C virus (HCV) genotype 3 directly induces development of steatosis, whereas in patients with non-genotype 3 chronic hepatitis C infection, insulin resistance plays a key role in the pathophysiology of steatosis. Insulin resistance and its clinical components including obesity, hyperglycemia, hypertriglyceridemia, increased blood pressure, and low HDL-cholesterol levels are often seen in patients with chronic hepatitis C infection. Both increased adipocity and presence of steatosis may increase the risk of fibrosis progression, and both have been associated with a decreased rate of response to antiviral treatment. Hence, liver steatosis in the setting of HCV infection is a distinct condition with specific clinical and prognostic implications. Accumulating evidence suggests that weight management may lead not only to a decrease in steatosis but also improvement in fibrosis severity. However, further studies are necessary to determine whether weight reduction improves response to antiviral therapy.
 ...
PMID:Hepatitis C and steatosis. 1761 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>