Lymphocyte proliferation inhibitory factor (PIF) in alcoholic liver disease. (1/3223)

Lymphocyte proliferation inhibitory factor (PIF) was determined in the supernatants of PHA-stimulated lymphocytes from patients with alcoholic liver disease. PIF was assayed by determining inhibition of DNA synthesis in WI-38 human lung fibroblasts. A two-fold greater inhibition in thymidine incorporation into DNA by lung fibroblasts was observed in supernatants of PHA stimulated lymphocytes from patients with alcoholic hepatitis or active Laennec's cirrhosis as compared with that found in control subjects or patients with fatty liver. It is suggested that decreased liver cell regeneration seen in some patients with alcoholic hepatitis may be due to increased elaboration of PIF.  (+info)

Preventive effects of dehydroepiandrosterone acetate on the fatty liver induced by orotic acid in male rats. (2/3223)

Preventive effects of dehydroepiandrosteone acetate (DHEA-A) and clofibrate (positive control substance) on the fatty liver induced by orotic acid (OA) were examined on the male Sprague-Dawley rats fed a high sucrose based diet containing 1% OA and this diet further mixed with 0.5% DHEA-A or 0.5% clofibrate for 2 weeks. Numerous lipid droplets were observed in the hepatocytes of the rats treated with OA alone, but not in those treated with DHEA-A or clofibrate. In comparison to the group with OA alone, the DHEA-A or clofibrate treated rats showed a larger relative liver weight (to body weight) which was accompanied by increased peroxisomes in the hepatocytes. These results indicate that DHEA-A, as well as clofibrate, may prevent OA-induced fatty liver.  (+info)

Liver disease in pregnancy. (3/3223)

Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute hepatitis is unaffected by pregnancy, except in patients with hepatitis E and disseminated herpes simplex infections, in which maternal and fetal mortality rates are significantly increased. Chronic hepatitis B or C infections may be transmitted to neonates; however, hepatitis B virus transmission is effectively prevented with perinatal hepatitis B vaccination and prophylaxis with hepatitis B immune globulin. Cholelithiasis occurs in 6 percent of pregnancies; complications can safely be treated with surgery. Women with chronic liver disease or cirrhosis exhibit a higher risk of fetal loss during pregnancy. Preeclampsia is associated with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome, acute fatty liver of pregnancy, and hepatic infarction and rupture. These rare diseases result in increased maternal and fetal mortality. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. Therapy with penicillamine, trientine, prednisone or azathioprine can be safely continued during pregnancy.  (+info)

Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death. (4/3223)

BACKGROUND: Genetic defects are being increasingly recognized in the etiology of primary cardiomyopathy (CM). Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first step in the beta-oxidation spiral of fatty acid metabolism, the crucial pathway for cardiac energy production. METHODS AND RESULTS: We studied 37 patients with CM, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis, features suggestive of fatty acid oxidation disorders. Single-stranded conformational variance was used to screen genomic DNA. DNA sequencing and mutational analysis revealed 21 different mutations on the VLCAD gene in 18 patients. Of the mutations, 80% were associated with CM. Severe CM in infancy was recognized in most patients (67%) at presentation. Hepatic dysfunction was common (33%). RNA blot analysis and VLCAD enzyme assays showed a severe reduction in VLCAD mRNA in patients with frame-shift or splice-site mutations and absent or severe reduction in enzyme activity in all. CONCLUSIONS: Infantile CM is the most common clinical phenotype of VLCAD deficiency. Mutations in the human VLCAD gene are heterogeneous. Although mortality at presentation is high, both the metabolic disorder and cardiomyopathy are reversible.  (+info)

Detection of haptoglobin in the high-density lipoprotein and the very high-density lipoprotein fractions from sera of calves with experimental pneumonia and cows with naturally occurring fatty liver. (5/3223)

In addition to the lipoprotein-deficient d > 1.25 fraction, haptoglobin was detected in the high-density lipoprotein (HDL) and the very high-density lipoprotein (VHDL) fractions from sera of calves with experimental pneumonia and cows with naturally occurring fatty liver. It was not found in the chylomicrons, very low-density lipoprotein and low-density lipoprotein fractions. Washing of the HDL fraction did not decrease the haptoglobin concentration. Transferrin and immunoglobulin G were immunoblotted to examine the possibility of contamination of the lipoprotein fractions by the d > 1.25 fraction. The two serum proteins were detected only in the d > 1.25 fraction, not in any lipoprotein fractions. The distribution pattern of haptoglobin in the lipoprotein fractions was distinct from that of serum albumin. Concentrations of haptoglobin in the HDL fractions from pneumonic sera were largely proportional to those in whole sera. Cholesteryl ester concentrations were decreased in sera from calves with pneumonia, as in cows with fatty liver. A protein immunologically related to hemoglobin was also detected in particular in the VHDL fractions from sera of both groups. These results suggest that haptoglobin or a complex with the hemoglobin-like protein may have a role or roles related to the lipid metabolism.  (+info)

Protection by short-chain fatty acids against 1-beta-D-arabinofuranosylcytosine-induced intestinal lesions in germfree mice. (6/3223)

In germfree mice, the administration of short-chain fatty acids (SCFA) protected the intestinal mucosa from damage produced by 1-beta-D-arabinofuranosylcytosine (Ara-C). Animals receiving SCFA and Ara-C had intestinal morphologies closer to normal than the control animals, which had severe intestinal lesions. We concluded that orally administrated SCFA reduce intestinal lesions, improving the mucosa pattern of the small intestine and colon.  (+info)

Fatty liver--an additional and treatable feature of the insulin resistance syndrome. (7/3223)

To test the hypothesis that fatty liver coexists with other metabolic abnormalities of the insulin resistance syndrome, and responds to their amelioration, we prospectively studied 48 consecutive patients with chronically elevated liver enzymes and clinical, ultrasound and histological findings consistent with fatty infiltration of the liver. Most of the patients were overweight or obese (64%) with increased waist circumference which closely relates to visceral fat. Only 10% of the patients had normal glucose tolerance: 44% had diabetes mellitus, 29% impaired glucose tolerance, and 17% were hyperinsulinaemic. The most common dyslipidaemia found was hypertriglyceridaemia and/or low HDL-C (86%). Dietary intervention and follow-up (median 24 months), supplemented by oral hypoglycaemic or lipid-lowering drugs as needed, resulted not only in weight loss (mean 3.7 kg), decreased fasting blood glucose (p < 0.005) and improvement in serum lipid profile (p < 0.02 for both triglycerides or HDL-C) but also in an improvement of serum liver enzymes in 96%, which became normal in more than half of the patients. Thus, fatty liver was strongly associated with many features of the insulin resistance syndrome, and follow-up revealed a high potential for reversibility and a benign course.  (+info)

A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women. (8/3223)

BACKGROUND: Acute fatty liver of pregnancy and the HELLP syndrome (hemolysis, elevated liver-enzyme levels, and a low platelet count) are serious hepatic disorders that may occur during pregnancy in women whose fetuses are later found to have a deficiency of long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase. This enzyme resides in the mitochondrial trifunctional protein, which also contains the active site of long-chain 2,3-enoyl-CoA hydratase and long-chain 3-ketoacyl-CoA thiolase. We undertook this study to determine the relation between mutations in the trifunctional protein in infants with defects in fatty-acid oxidation and acute liver disease during pregnancy in their mothers. METHODS: In 24 children with 3-hydroxyacyl-CoA dehydrogenase deficiency, we used DNA amplification and nucleotide-sequence analyses to identify mutations in the alpha subunit of the trifunctional protein. We then correlated the results with the presence of liver disease during pregnancy in the mothers. RESULTS: Nineteen children had a deficiency only of long-chain 3-hydroxyacyl-CoA dehydrogenase and presented with hypoketotic hypoglycemia and fatty liver. In eight children, we identified a homozygous mutation in which glutamic acid at residue 474 was changed to glutamine. Eleven other children were compound heterozygotes, with this mutation in one allele of the alpha-subunit gene and a different mutation in the other allele. While carrying fetuses with the Glu474Gln mutation, 79 percent of the heterozygous mothers had fatty liver of pregnancy or the HELLP syndrome. Five other children, who presented with neonatal dilated cardiomyopathy or progressive neuromyopathy, had complete deficiency of the trifunctional protein (loss of activity of all three enzymes). None had the Glu474Gln mutation, and none of their mothers had liver disease during pregnancy. CONCLUSIONS: Women with acute liver disease during pregnancy may have a Glu474Gln mutation in long-chain hydroxyacyl-CoA dehydrogenase. Their infants are at risk for hypoketotic hypoglycemia and fatty liver.  (+info)