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)

The most known risk factor for nonalcoholic fatty liver disease (NAFLD) is the metabolic syndrome. In this study, we characterized changes in liver pathology, hepatic lipid composition, and hepatic iron concentration (HIC) occurring in rats given fructose-enriched diet (FED), with and without therapeutic maneuvers to reduce blood pressure and plasma triglycerides. Rats were given FED or standard rat chow for 5 weeks. Rats on FED were divided into 4 groups: receiving amlodipine (15 mg/kg per day), captopril (90 mg/kg per day), bezafibrate (10 mg/kg per day) in the last 2 weeks, or a control group that received FED only. FED rats had hepatic macrovesicular and microvesicular fat deposits develop, with increase in hepatic triglycerides (+198%) and hepatic cholesterol (+89%), but a decrease in hepatic phospholipids (-36%), hypertriglyceridemia (+223%), and hypertension (+15%), without increase in HIC. Amlodipine reduced blood pressure (-18%), plasma triglycerides (-12%), but there was no change in hepatic triglycerides and phospholipids concentrations. Captopril reduced blood pressure (-24%), plasma triglycerides (-36%), hepatic triglycerides (-51%), and hepatic macrovesicular fat (-51%), but increased HIC (+23%), with a borderline increase in hepatic fibrosis. Bezafibrate reduced plasma triglycerides (-49%), hepatic triglycerides (-78%), hepatic macrovesicular fat (-90%), and blood pressure (-11%). We conclude that FED rats can be a suitable model for human NAFLD. Drugs administered to treat various aspects of the metabolic syndrome could have hepatic effects. An increase in HIC in rats with NAFLD could be associated with increased hepatic fibrosis.
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PMID:Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction. 1582 94

Hepatic steatosis is the hallmark of nonalcoholic fatty liver disease (NAFLD), which is the consequence of multiple metabolic derangements among which insulin resistance plays a pivotal role. Steatosis is, also, a feature of hepatitis C virus (HCV) infection. However, in chronic hepatitis C, the prevalence of steatosis is 2.5-fold more elevated than that expected by a chance concurrence with NAFLD, suggesting that HCV may be implied in the development of steatosis. As observed in NAFLD, in patients infected with HCV genotype 1 steatosis is associated with an increased body mass index. On the other hand, in patients infected with genotype 3 the extent of steatosis strictly correlates with the viral load indicating that steatosis is mainly "virus-related". Regardless of the "metabolic" or "viral" etiology, hepatic steatosis in HCV contributes to the progression of liver fibrosis, to the development of hepatocellular carcinoma and to an impaired response to interferon treatment. Features such as obesity, insulin resistance and type 2 diabetes mellitus are shared by NAFLD and HCV-associated steatosis. In addition, HCV infection, directly or through steatosis, favors the development of type 2 diabetes mellitus. Hyperlipidemia is an independent predictor of the development of NAFLD, but not of HCV-associated steatosis. Arterial hypertension is common in nonalcoholic steatohepatitis patients, and HCV infection has recently been acknowledged as an independent risk factor for atherosclerosis. The role of iron in the progression of both NAFLD and HCV-associated steatosis remains controversial while lipoperoxidation and oxidative stress are pathogenic mechanisms shared by both. Some metabolic risk factors may be shared by both HCV-associated steatosis and NAFLD although the disease progression and pathophysiological background may be different. Preliminary data suggest that the therapeutic options for NAFLD may also be useful to improve HCV-associated steatosis.
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PMID:[Hepatitis C virus-associated and metabolic steatosis. Different or overlapping diseases?]. 1585 90

The hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide, with approximately 170-200 million people infected. The HCV virus is transmitted by blood and blood products and such transmission occurs primarily through drug use by injection, sex with an infected partner and occupational exposure. The severity of the disease varies widely from mild chronic hepatitis to cirrhosis and hepatocellular carcinoma (HCC). Nowadays, the reference treatment is combination therapy of pegylated interferon and ribavirin, which is an inosine monophosphate dehydrogenase inhibitor and immunomodulator. Efficacy of treatment in our clinical trials is 87% in patients infected by HCV genotypes 2 or 3, whereas in patients infected by HCV genotype 1 response to treatment is 66%. The current combination treatment has significant side-effects and sometimes is poorly tolerated. HCV genotypes 2 or 3 can be treated with a lower dose of ribavirin and a shorter course of therapy, 24 weeks vs 48 weeks for patients with genotype 1. There is a growing consensus that acute control of HCV infection is associated with a vigorous intrahepatic antiviral CD4+ and CD8+ T-cell response, enhanced Th1 and natural killer activity. Pretreatment genotype and response to therapy measured at weeks 12 and 24 of treatment have been identified as key determinants in decisions about continuing treatment. Elevated serum ferritin levels and hepatic iron deposition as well as hepatic steatosis and high ALT levels with chronic hepatitis C are risk factors for HCC development. Heterozygosityfor the C282Y mutation in HFE contributes to iron accumulation and fibrosis progression in chronic hepatitis C. Ribavirin could cause dose-dependent reversible haemolytic anaemia, which can be managed with dose reductions or with administration of epoetin alpha at 40,000 IU once weekly without sacrificing the optimal dosing of ribavarin. Among patients who received ribavirin alone, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels and hepatic fibrosis scores were not changed significantly from baseline. For HCV-HIV co-infected patients, treatment is given when blood CD4 counts are above 350/ml and before antiretroviral (ART) treatment is needed.
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PMID:Ribavirin in the treatment of hepatitis C. 1586 84

The challenges of growing prevalence and evident trend to progressive damage of primary nonalcoholic fatty liver disease confront a poorly understood pathogenesis. It appears to develop in two steps. First, a high adipocyte protein production in the context of a silent inflammatory background causes insulin resistance in adipose tissue. It leads both to lipolysis, with increase of the circulating and hepatic uptake of free fatty acids, and hyperinsulinemia. Within hepatocytes, the subsequent lipogenesis, together with a decreased secretion of lipoproteins, induces an accumulation of excessive hepatic triglycerides (steatosis), impliying some oxidative damage, but it remain balanced by uncoupling protein upregulation and antioxidant systems activation. Second, a more forceful fat catabolism by beta and omega oxidation results in respiratory chain hyperactivity with overproduction of free radicals and reactive oxygen species that exceed the antioxidant capacity. These agents lead to hepatocellular injury and necrosis, inflammatory infiltration and fibrosis (steatohepatitis) through induction of Fas ligand and cytokines (tumor necrosis factor alpha, transforming growth factor beta, interleukin-8), and lipid peroxidation and by-products (malondialdehyde and 4-hydroxynonenal). Other mechanisms (hepatic iron, Kupffer cells dysfunction or endotoxemia) play uncertain roles.
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PMID:[Pathogenesis of primary nonalcoholic fatty liver disease]. 1588 16

Thioredoxin (TRX) is induced by many oxidative stresses. Serum TRX levels were significantly elevated in nonalcoholic steatohepatitis (NASH) patients, as compared to simple fatty liver (FL) patients or healthy controls. Serum TRX levels in NASH patients were significantly correlated with serum ferritin levels, but not with other variables. Removal of hepatic excess iron by phlebotomy significantly decreased the serum levels of TRX and ALT in NASH patient. Therefore, the pathogenesis of NASH may be associated with iron-related oxidative stress. The serum TRX level is a parameter for discriminating NASH from FL.
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PMID:Elevation of serum thioredoxin levels in patients with nonalcoholic steatohepatitis. 1625 59

Hepatic iron has been described in hepatitis C virus (HCV) infection as an important cofactor of disease outcome. The mechanisms leading to hepatic iron deposits (HIDs) in HCV patients are partially understood. We investigated HIDs in the liver biopsies of a consecutive series of 242 HCV-infected patients with well-compensated liver disease. Serum ferritin was elevated in 20.7% and transferrin saturation in 19.0%, while 38.8% had stainable HIDs indicating that serum markers of systemic iron overload have low sensitivity in predicting HIDs in hepatitis C. A cut-off value of serum ferritin (350 microg/L in females and 450 microg/L in males) had good negative predictive value in excluding presence of mild-moderate HIDs (grade II-III). Hepatic iron deposits correlated by multivariate analysis with serum ferritin [odds ratio (OR) 1.008, 95% confidence interval (CI) 1.005-1.011] and albumin (OR 1.15, 95% CI 1.02-1.297). Hepatic iron deposits were more frequent in HCV-3-infected cases than in other genotypes (P = 0.027) while raised serum iron indices were more frequent in non-HCV-3 genotypes (P = 0.02). Furthermore, advanced fibrosis (F3-F4 by METAVIR) was more frequent in non-HCV-3 genotypes (P = 0.04). In HCV-3 cases there was a close association between HIDs and severe (grade II-III) steatosis (P < 0.00001). These results indicate that in well-compensated chronic hepatitis C HIDs are strongly associated with HCV-3 and viral-induced hepatic steatosis, while in the presence of other genotypes they might merely reflect a more advanced stage of liver disease and/or a systemic iron overload. Serum ferritin could identify a subgroup of patients in which the need of venesection could be excluded without liver biopsy.
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PMID:Hepatic iron, liver steatosis and viral genotypes in patients with chronic hepatitis C. 1647 96

Nonalcoholic steatohepatitis/nonalcoholic fatty liver disease is considered to be a hepatic manifestation of various metabolic disorders. However, its precise pathogenic mechanism is obscure. Oxidative stress and consequent lipid peroxidation seem to play a pivotal role in disease progression. In this study, we analyzed the localization of oxidized phosphatidylcholine (oxPC), a lipid peroxide that serves as a ligand for scavenger receptors, in livers of patients with this steatotic disorder. Specimens of non-alcoholic fatty liver disease (15 autopsy livers with simple steatosis and 32 biopsy livers with steatohepatitis) were examined via immunohistochemistry and immunoelectron microscopy using a specific antibody against oxPC. In addition, scavenger receptor expression, hepatocyte apoptosis, iron deposition, and inflammatory cell infiltration in the diseased livers were also assessed. Oxidized phosphatidylcholine was mainly localized to steatotic hepatocytes and some macrophages/Kupffer cells. A few degenerative or apoptotic hepatocytes were also positive for oxPC. Immunoelectron microscopy showed oxPC localized to cytoplasmic/intracytoplasmic membranes including lipid droplets. Steatotic livers showed enhanced expression of scavenger receptors. The number of oxPC cells was correlated with disease severity and the number of myeloperoxidase-positive neutrophils, but not with the degree of iron deposition. In conclusion, distinct localization of oxPC in liver tissues suggest that neutrophil myeloperoxidase-derived oxidative stress may be crucial in the formation of oxPC and the progression of steatotic liver disease.
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PMID:Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: impact on disease progression. 1649 25

To study the clinical correlates of the H63D mutation we have analysed the phenotype of H63D homo-zygotes identified through mutation analysis in a referral laboratory. A total of 366 blood samples referred for HFE analysis were screened for C282Y and H63D mutations. Four H63D homozygotes were identified. All had raised serum ferritin but normal transferrin saturation. They were negative for hepatitis B and C and only one patient consumed excess alcohol. In all 4 cases ultrasonography revealed fatty liver. In two patients a liver biopsy was done and showed mild siderosis with an unusual distribution and macrovesicular steatosis. These data confirm the association between fatty liver, hyperferritinaemia and increased hepatic iron, but do not clarify whether siderosis was related to steatosis rather than homozygosity for the H63D mutation. Patients with fatty liver may complicate the interpretation of data in population studies of the expression of H63D homozygosity.
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PMID:Fatty liver in H63D homozygotes with hyperferritinemia. 1658 55

Hepatic iron overload in hemochomatosis patients can be highly variable but in general it develops in older patients. The purpose of this study was to compare development of iron load in of beta2m-/- and Hfe-/- mice paying special attention to liver pathology in older age groups. Liver iron content of beta2m-/-, Hfe-/- and control B6 mice of different ages (varying from 3 weeks to 18 months) was examined. Additional parameters (haematology indices, histopathology, lipid content and ferritin expression) were also studied in 18-month-old mice. The beta2m-/- strain presents higher hepatic iron content, hepatocyte nuclear iron inclusions, mitochondria abnormalities. In addition, hepatic steatosis was a common observation in this strain. In the liver of Hfe-/- mice, large mononuclear infiltrates positive for ferritin staining were commonly observed. The steatosis commonly observed the beta2m-/- mice may be a reflection of its higher hepatic iron content. The large hepatic mononuclear cell infiltrates seen in Hfe-/- stained for ferritin, may point to the iron sequestration capacity of lymphocytes and contribute to the clarification of the differences found in the progression of hepatic iron overload and steatosis in older animals from the two strains.
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PMID:Comparative study between Hfe-/- and beta2m-/- mice: progression with age of iron status and liver pathology. 1687 97

Chronic liver diseases are disastrous to health. Many factors are associated with their prevalence, hence endemicity. These are mainly infectious, parasitic and toxic. A survey was conducted in a village south to Cairo. Large industries concerned with iron and steel industry, metals smelting, cement manufacturing and electric station were located north to the village. A systematic random sample of houses was selected. All individuals inside the houses were invited to share in the study. Sample size was 84 individuals. Hepatitis markers were done (HBsAg and anti-HCV antibodies). The levels of some heavy metals were assessed; which were lead, mercury, arsenic, aluminum, manganese, nickel, chromium and cadmium. Levels of some trace elements were assessed. These were copper, iron, selenium and zinc. Aflatoxin B1 was assessed in serum. Assessment of schistosomal circulating antigen and antibodies was carried out. Abdominal ultrasonograghy was done to assess liver condition. Univariate logistic regression analysis was done to assess the association between studied variables and HBsAg or anti-HCV sero-positive subjects. The association between studied variables and bilharzial or fatty liver, diagnosed by ultrasonography, were also assessed. The univariate logistic regression analysis revealed odds ratios at the following results. For HBsAg seropositive subjects, aflatoxin B1, lead, chromium and schistosomal antigen and antibodies were higher than negative ones where odds ratios were; 6.2, 1.6, 1.6, 1.6 and 1.7, respectively. None of the variables showed statistically significant difference. For anti-HCV antibodies sero-positive subjects, aflatoxin B1 and chromium had the highest odds ratios among the studied variables, (odds ratios were 2.5 and 2.4, respectively). Bilharzial liver showed higher significant positivity of anti-HCV antibodies and insignificant decreased level of zinc than negative ones (odds ratios were 7.2 and 4.5, respectively). Fatty liver cases showed higher statistically significant positivity of anti-HCV antibodies and chromium than negative ones. Odds ratios were 8.0 and 7.1, respectively. Statistically significant lower level of aflatoxin B1 was shown in fatty liver than normal liver subjects. Multivariate logistic regression analysis for fatty liver showed that only anti-HCV antibodies sero-positivity had statistically significant odds ratio in comparison to chromium level and aflatoxin B1. It is concluded that some heavy metals, and Aflatoxin B1 had a definite association with liver diseases in the area under study. Having anti-HCV antibodies had a relation with fatty liver and with bilharzial liver more than having HBsAg. It is recommended that environmental management to factories nearby the village is urgently needed to decrease exposure to heavy metals. Prevention of hepatitis infection and aflatoxin exposure through different means is also recommended, other wise health care authorities would be confronted with unusual cases of HCC in the nearby future.
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PMID:A cross sectional study of hepatitis B, C, some trace elements, heavy metals, aflatoxin B1 and schistosomiasis in a rural population, Egypt. 1690 Jun 14


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