Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective, randomized, double-blind therapeutic trial, 191 patients with non-alcoholic steatohepatitis were treated for 8 weeks daily b.i.d. orally either with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate (Ietepar) (96 patients) or with undistinguishable placebo capsules (95 patients). The verum treatment effectively reduced by 25% hepatic steatosis (p < 0.01) and by 6% hepatomegaly (p < 0.05), while placebo did not significantly reduce the disorders. Verum was also more effective than placebo on discomfort in abdominal upper right quadrant. The global efficacy of treatment was rated by the doctor "very good" or "good" in 48% of verum treated patients and only in 17% after placcbo (P of difference = 9 x 10(-6)). 52% of patients self-rated efficacy as "very good" or "good" after verum and only 34% after placebo (P of difference = 0.017). The verum treatment provoked a significant reduction of the increased liver transaminases (ALT, AST and gamma-GT) while placebo was ineffective. Adverse events were recorded in 10% of verum-treated patients and in 7% under placebo (no significant difference). In both groups the adverse events were mild and transient, did not require treatment discontinuation and were undistinguishable from common symptoms of liver disorders. In conclusion, the 8-week treatment with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate was found effective in non-alcoholic steatohepatitis, a disorder for which the hitherto pharmacological interventions were poorly and inconsistently effective.
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PMID:Efficacy and safety of oral betaine glucuronate in non-alcoholic steatohepatitis. A double-blind, randomized, parallel-group, placebo-controlled prospective clinical study. 1099 56

Hemochromatosis is one of the most frequent genetic diseases among the white populations, affecting one in three hundred persons. Its diagnosis has been radically transformed by the discovery of the HFE gene. In a given individual, the diagnosis can, from now on, be ascertained on the sole association of a plasma transferrin saturation (TS) over 45% and homozygosity for the C282Y mutation. Liver biopsy is only required to search for cirrhosis whenever there is hepatomegaly and/or serum ferritin >1000 ng/ml and/or elevated serum AST. Family screening is mandatory, primarily centered on the siblings. The treatment remains based on venesection therapy which improves many features of the disease (one of the most refractory, however, being the joint signs) and permits normal life expectancy provided the diagnosis is established prior to the development of cirrhosis or of insulin-dependent diabetes. In view of the prevalence, the non-invasive diagnosis, the spontaneous severity and the efficacy of a very simple therapy, hemochromatosis should benefit from population screening. This screening could be based, first, on the assessment of transferrin saturation, followed - when elevated - by the search for the C282Y mutation. The discovery of the HFE gene has also paved the road for the individualization of other types of iron overload syndromes which are not HFE-related.
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PMID:Clinical aspects of hemochromatosis. 1109 95

Autoimmune hepatitis is one of the causes of chronic progressive liver disease in childhood. Here we report 14 cases with clinical findings, therapeutic management and prognosis, in order to define the course of the disease. Diagnosis of autoimmune hepatitis was done with the presence of at least one of these autoantibodies; antinuclear antibody, smooth muscle antibody, liver-kidney microsomal type 1 antibody, and perinuclear antineutrophilic cytoplasmic antibody. Patients were seen every 3 to 6 months. After doing a complete physical examination, biochemical parameters and autoantibodies determined at each visit. Mean age at diagnosis was 10.9 +/- 2.6 years (range, 7-15.5 years) and female to male ratio was 1:3. Thirteen patients had jaundice and all had high levels of ALT, AST and gammaglobulin. Hepatomegaly was found in 71.4% and splenomegaly in 64.3% of the patients. All patients were classified as type 1 autoimmune hepatitis. Liver biopsies revealed severe active hepatitis with mononuclear cell infiltration in portal areas, piecemeal necrosis. Drug therapy consisted of prednisone (2 mg/kg/day) per oral at the beginning, and addition of azathioprine (1.5 mg/kg/day) per oral at the 3rd-6th month with slow tapering of prednisone in 12 children. Both drugs were started together to two patients. Follow-up period was 30.7 +/- 15.6 months (range, 12-72 months). Sustained normalization of ALT could not be obtained with tapering doses of prednisone alone. Decrease in ALT levels did not correlate with disappearance of serum autoantibodies. None of the patients showed decompensation of liver disease. Azathioprine administration is necessary to decrease prednisone dose and to maintain a sustained normal transaminase values.
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PMID:Autoimmune hepatitis. 1156 49

Human fascioliasis is increasing in the Nile Delta particularly in Dakahlia Governorate, where it reached 7.47%. In this study, the tetrad of fascioliasis was established as high eosinophilia (100%), fever (85.6%), painful hepatomegaly (81.93%) and anaemia (100%). The laboratory results showed ESR accelerated in 87%, ALT elevated in 21.5%, AST elevated in 21.9%, S. bilirubin elevated in 16.5%, gamma GT elevated in 80.6%, and SAP elevated in 76.4%. Abdominal ultrasonography showed variable findings, as hepatomegaly, splenomegaly, periportal fibrosis, thickened wall of gall bladder, dilated common bile duct, dilated biliary radicals (partial), dilated common bile duct and biliary radicals (total), Fasciola worms in gall bladder, Fasciola worms in common bile duct, stones in gall bladder, stones in bile duct, cystic lesions in the liver, local lesions in the liver and ascitis. The highest was hepatomegaly in 81.93% of fascioliasis patients and the lowest was biliary dilated radicles (partial) in 0.26%.
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PMID:Clinico-epidemiological study of human fascioliasis in an endemic focus in Dakahlia Governorate, Egypt. 1177 99

Beta-cyclodextrin is a compound that forms inclusion complexes with a variety of molecules, specially bile acids and sterols. This study examines the effects of beta-cyclodextrin on cholesterol and bile acid metabolism in hypercholesterolaemic rats. Male Wistar rats were divided into 4 groups that received during 7 weeks: control diet, 2% cholesterol diet (A), A+2.5% beta-cyclodextrin (B) and A+5% beta-cyclodextrin (C). The cholesterol-rich diet induced hepatomegaly and fatty liver and significantly reduced cholesterol, bile acid and phospholipid secretion. Addition of beta-cyclodextrin normalised biliary lipid secretion. Moreover, when compared to A, beta-cyclodextrin significantly lowered plasma phospholipid concentration (B: -21%; C: -29%) and the liver free/total cholesterol molar ratio (B: -40%; C: -38%), increased bile acid faecal output (B: +17%; C: +62%) and enhanced cholesterol 7alpha-hydroxylase activity (B:+50%; C : +100%)and mRNA levels (B: + 14%; C: +29%). 5% beta-cyclodextrin also reduced plasma triglycerides concentration (-38%). However, ALT and AST activities were significantly increased (B: +140% and +280%; C: +72% and +135%) and there was a high incidence of cell necrosis with portal inflammatory cell infiltration. Addition of beta-cyclodextrin to a cholesterol-rich diet results in a triglyceride-lowering action, enhancement of bile acid synthesis and excretion, and normalization of biliary lipid secretion, but produces a marked hepatotoxic effect.
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PMID:Effects of dietary beta-cyclodextrin in hypercholesterolaemic rats. 1274 79

With the aim of establishing bio-indices for the development of multistep hepatotumorigenesis, rats were fed water containing 0.01% diethylnitrosamine (DEN) ad libitum for 13 weeks. This treatment with DEN only made it possible to induce hepatic tumors in 100%. After the DEN administration, several clinical symptoms were observed including minor behavioral changes, brittleness of hair and a decrease in water and food intake. The concentration of total serum protein and albumin in all treated groups was significantly lower than in non-treated controls (P<0.05). Increase of specific enzyme (AST, ALT and GGT) activity (P<0.05), variable tumor size and hepatomegaly of the liver was observed in all rats treated with DEN for 10 weeks. Both hepatocellular carcinoma and cholangiocarcinoma were found in the same livers at the same time, and were prominently developed after 12 weeks. In case of carcinoma, some of the livers showed more or less advanced states over the 12-15 weeks period. In the present study, hepatocellular carcinoma was developed by treating DEN in only the drinking water, without any other carcinogens or without partial hepatectomy. These results indicate that DEN is a new carcinogen that acts directly on it the liver, moreover, it might be very useful for investigating hepatotumorigenesis.
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PMID:Study on mechanism of multistep hepatotumorigenesis in rat: development of hepatotumorigenesis. 1461 95

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors whose ligands include fatty acids, eicosanoids and the fibrate class of drugs. In humans, fibrates are used to treat dyslipidemias. In rodents, fibrates cause peroxisome proliferation, a change that might explain the observed hepatomegaly. In this study, rats were treated with multiple dose levels of six fibric acid analogs (including fenofibrate) for up to two weeks. Pathological analysis identified hepatocellular hypertrophy as the only sign of hepatotoxicity, and only one compound at the highest dose caused any significant increase in serum ALT or AST activity. RNA profiling revealed that the expression of 1288 genes was related to dose or length of treatment and correlated with hepatocellular hypertrophy. This gene list included expression changes that were consistent with increased mitochondrial and peroxisomal beta-oxidation, increased fatty acid transport, increased hepatic uptake of LDL-cholesterol, decreased hepatic uptake of glucose, decreased gluconeogenesis and decreased glycolysis. These changes are likely linked to many of the clinical benefits of fibrate drugs, including decreased serum triglycerides, decreased serum LDL-cholesterol and increased serum HDL-cholesterol. In light of the fact that all six compounds stimulated similar or identical changes in the expression of this set of 1288 genes, these results indicate that hepatomegaly is due to PPARalpha activation, although signaling through other receptors (e.g. PPARgamma, RXR) or through non-receptor pathways cannot be excluded.
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PMID:Profiling of hepatic gene expression in rats treated with fibric acid analogs. 1512 Sep 67

The aim of the study was to identify moderate liver impairment in a group of hyperbilirubinaemic adolescents. Using gas chromatography we assessed both total bile acid and primary bile acid levels in 50 adolescents with juvenile hyperbilirubinaemia. At the same time we performed hepatologic examinations and subsequent follow-up assessment of these patients for a period of at least 2 years. As a control group we examined 30 adolescents without any impairment of both the liver and gastrointestinal tract, and 18 patients with low grade (moderately) active chronic hepatitis. In both groups we assessed total and primary bile acids levels as well as conventional liver tests (bilirubin, ALT, AST). On the basis of the clinical course and laboratory findings we divided our patients with juvenile hyperbilirubinaemia into two groups: a group of individuals with Gilbert's syndrome (30 patients) and a group of individuals with probable moderate liver impairment (20 patients). The latter group consisted of the adolescents who exhibited bilirubinaemia over 90 micromol/l and/or exhibited hepatomegaly or splenomegaly proved by the ultrasound examination and/or exhibited intermittent elevation of the liver aminotransferases serum levels. In the group of individuals with moderate liver impairment serum total bile acid levels were significantly elevated in 26% of patients, and the serum cholic acid level was significantly elevated in 25% of patients. These two parameters mutually correlated at a high level of significance. Juvenile hyperbilirubinaemia is one of the common conditions of adolescent age. Its etiology is diverse; it includes both benign conditions like Gilbert's syndrome and post-hepatitic and toxic conditions that require a long-term regimen and follow-up examinations. The number of people suffering from juvenile hyperbilirubinaemia has been growing in the population. Currently 4-6% of the adolescent population suffers from this disease. This growing number is probably caused by external factors of our environment (infection, toxic effects). The determination of mild liver disease in hyperbilirubinaemic patients and the provision of an adequate regimen of exercise and adequate nutritional measures is of great importance for the health of the adolescent population.
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PMID:Importance of serum bile acids determination in adolescents with juvenile hyperbilirubinaemia. 1524 29

A 16-year-old Caucasian girl of Albanian origin was admitted to the hospital complaining of intermittent fever (38 degrees C) for a week, nausea, vomiting, and abnormal laboratory findings (elevated serum aminotransferases levels AST/ALT 77/40 U/l and erythrocyte sedimentation rate 80 mm/first hour, as well as leukopenia 2.5 x 10(3)/mm3), which were found in a blood examination. Physical examination revealed slight hepatomegaly and splenomegaly, as well as cervical and axillary lymphadenopathy. A diagnostic open lymph node biopsy was performed and Kikuchi-Fujimoto disease (KFD) was established based on the characteristic histological pattern. Other abnormal laboratory findings were C-reactive protein 6.8 mg/dl and serum lactate dehydrogenase 900 U/l. Her history included a diarrhoea syndrome 2 months before the present admission, during the summer holidays, for which she was treated with metronidazole. At that time, characteristic cysts of giardia lamblia intestinalis were observed in the stools. Herein, we present this case hypothesising that the protozoal infection caused by the giardia lamblia intestinalis was probably triggering an immune response leading to KFD. The patient's age in combination with this firstly reported protozoal pathogen, as a triggering agent leading to KFD, consist a very interesting originality. Additionally, some review data is also given.
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PMID:Giardia lamblia intestinalis: a new pathogen with possible link to Kikuchi-Fujimoto disease. An additional element in the disease jigsaw. 1564 21

Severe lipodystrophy is characterized by diminished adipose tissue and hypoleptinemia, leading to ectopic triglyceride accumulation. In the liver, this is associated with steatosis, potentially leading to nonalcoholic steatohepatitis (NASH). We investigated the prevalence of NASH and the effect of leptin replacement in these patients. Ten patients with either generalized lipodystrophy (8 patients) or Dunnigan's partial lipodystrophy (2 patients) were included in this analysis. Paired liver biopsy specimens were obtained at baseline and after treatment with recombinant methionyl human leptin (r-metHuLeptin), mean duration 6.6 months. The extents of portal and parenchymal inflammation, steatosis, ballooning, presence of Mallory bodies, and fibrosis in liver biopsy specimens were scored using a previously validated system developed to assess NASH activity. Histological disease activity was defined as the sum of ballooning, steatosis, and parenchymal inflammation scores. We concurrently tested serum triglycerides and aminotransferases and estimations of liver volume and fat content by magnetic resonance imaging. Eight of 10 patients met histological criteria for NASH at baseline. After treatment with r-metHuLeptin, repeat histological examinations showed significant improvements in steatosis (P = .006) and ballooning injury (P = .005), with a reduction of mean NASH activity by 60% (P = .002). Fibrosis was unchanged. Significant reductions were seen in mean serum triglycerides (1206-->226 mg/dL, P = .002), glucose (220-->144 mg/dL, P = .02), insulin (46.4-->24.8 muIU/mL, P = .004), ALT (54-->24 U/L, P = .02), AST (47-->22 U/L, P = .046), liver volume (3209-->2391 cm(3), P = .007), and liver fat content (31-->11%, P = .006). In conclusion, r-metHuLeptin therapy significantly reduced triglycerides, transaminases, hepatomegaly, and liver fat content. These reductions were associated with significant reductions in steatosis and the hepatocellular ballooning injury seen in NASH.
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PMID:Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy. 1579 19


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