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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine whether the minimum necessary volume of a moderate fatty liver graft was similar to the normal liver volume and to elucidate means for improving the function of the transplanted fatty liver if it were inferior in volume to a normal liver under conditions of permissible cold preservation. Nine-week-old male Wistar rats were used. Normal rat chow was fed to the normal liver group, and fat-enriched rat chow was fed to the fatty liver group for 4 weeks to induce a moderately fatty liver. Liver transplantation with various volumes of reduced-size grafts, including whole liver graft (100%LT), 70% volume graft (70%LT), and 30% volume graft (30%LT), was performed with both groups of rats as donors. All procedures were performed under the conditions of 2-hour cold preservation. All rats with an implanted normal liver were surviving at 7 days after the operation regardless of the graft volume (100%LT, 5 of 5; 70%LT, 5 of 5; 30%LT, 5/5). In contrast, the survival rates decreased according to the graft volume in rats implanted with fatty livers (100%LT, 8 of 8; 70%LT, 5 of 8; 30%LT, 2/8). To improve the survival of 30%LT with fatty liver, we employed two potent inhibitors of ischemia-reperfusion injury: FK506 and prostaglandin E1. Though FK506 had no advantageous effect, prostaglandin E1 significantly improved the survival rate and diminished serum levels of alanine aminotransferase and hyaluronic acid. In conclusion, the volume of graft necessary for successful transplantation is larger in fatty livers than in normal livers in permissible cold preservation. Also, prostaglandin E1 protects grafts against ischemia-reperfusion injury and improves the functioning of a transplanted fatty liver.
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PMID:Prostaglandin E1 improved the function of transplanted fatty liver in a rat reduced-size-liver transplantation model under conditions of permissible cold preservation. 1251 77

Ob/ob mice, a model for nonalcoholic fatty liver disease (NAFLD), develop intestinal bacterial overgrowth and overexpress tumor necrosis factor alpha (TNF-alpha). In animal models for alcoholic fatty liver disease (AFLD), decontaminating the intestine or inhibiting TNF-alpha improves AFLD. Because AFLD and NAFLD may have a similar pathogenesis, treatment with a probiotic (to modify the intestinal flora) or anti-TNF antibodies (to inhibit TNF-alpha activity) may improve NAFLD in ob/ob mice. To evaluate this hypothesis, 48 ob/ob mice were given either a high-fat diet alone (ob/ob controls) or the same diet + VSL#3 probiotic or anti-TNF antibodies for 4 weeks. Twelve lean littermates fed a high-fat diet served as controls. Treatment with VSL#3 or anti-TNF antibodies improved liver histology, reduced hepatic total fatty acid content, and decreased serum alanine aminotransferase (ALT) levels. These benefits were associated with decreased hepatic expression of TNF-alpha messenger RNA (mRNA) in mice treated with anti-TNF antibodies but not in mice treated with VSL#3. Nevertheless, both treatments reduced activity of Jun N-terminal kinase (JNK), a TNF-regulated kinase that promotes insulin resistance, and decreased the DNA binding activity of nuclear factor kappaB (NF-kappaB), the target of IKKbeta, another TNF-regulated enzyme that causes insulin resistance. Consistent with treatment-related improvements in hepatic insulin resistance, fatty acid beta-oxidation and uncoupling protein (UCP)-2 expression decreased after treatment with VSL#3 or anti-TNF antibodies. In conclusion, these results support the concept that intestinal bacteria induce endogenous signals that play a pathogenic role in hepatic insulin resistance and NAFLD and suggest novel therapies for these common conditions.
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PMID:Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. 1288 98

Insulin resistant metabolic syndrome is a major clinical disorder including hyperlipidaemia, hypertension, impaired glucose tolerance and/or type 2 diabetes and central obesity, which are well established cardiovascular risk factors. We report the case of a 61-year-old woman who developed severe hypercholesterolaemia and hypertriglyceridaemia after liver transplantation. In her forties she had hypertension, mixed hyperlipidaemia, mild hyperglycaemia and moderate abdominal obesity, suggesting the presence of the metabolic syndrome. She had liver enzyme elevation and severe steatosis and hepatomegaly at ultrasonography. At age 52, cryptogenic liver cirrhosis was diagnosed and rapidly progressing liver failure developed. In 1992 she underwent liver transplantation. Seven years after transplant the patient had abdominal obesity, high blood pressure, marked hypercholesterolaemia, hypertriglyceridaemia and moderate elevation of alanine aminotransferase. She also had impaired glucose tolerance and markedly increased basal and post-glucose load plasma insulin levels. Steatohepatitis was demonstrated by serial liver biopsies. This is the first case that reports the recurrence of the metabolic syndrome following liver transplantation. We postulate that metabolic syndrome may have promoted fatty liver and subsequent progression to end stage liver disease. We also stress the need for careful management of the metabolic syndrome in order to decrease the long-term risk for cardiovascular disease.
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PMID:Recurrence of insulin resistant metabolic syndrome following liver transplantation. 1254 3

Acute ethanol exposure causes liver injury in experimental animals, and accumulating evidence suggests that a major responsible factor for the pathogenesis is endotoxemia, which results from bacterial endotoxin leakage from the small intestine due to increased intestinal permeability under alcohol challenge. The purpose of this study was to examine whether zinc pretreatment would inhibit acute ethanol-induced liver injury through prevention of intestinal permeability changes. Male 129 SvPCJ mice were treated with three intragastric doses of ZnSO4 at 5 mg of zinc ion per kg each dosing prior to acute ethanol challenge with a single oral dose of 6 g/kg ethanol. The zinc treatment did not alter the elevation of serum concentrations of alcohol. The acute ethanol exposure caused an elevation in serum alanine aminotransferase levels as well as fatty liver and hepatic degenerative necrotic foci as determined by biochemical assay and histochemical analysis, respectively. A significant increase in liver tumor necrosis factor-alpha (TNF-alpha) levels was detected by enzyme-linked immunosorbent assay. These pathological effects correlated well with increases in serum endotoxin levels. Importantly, acute ethanol treatment caused significant damage to the small intestine as determined by morphological analysis of intestinal sections and permeability assay. These alcohol-induced hepatic pathological changes and TNF-alpha elevation were significantly inhibited in the zinc-pretreated animals. The inhibitory action of zinc on alcohol-induced liver damage and activation of inflammation was associated with zinc suppression of alcohol-induced intestinal permeability changes. These results thus demonstrate that zinc prevention of increased intestinal permeability is importantly involved in the inhibition of acute ethanol-induced liver damage in mice.
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PMID:Prevention of alterations in intestinal permeability is involved in zinc inhibition of acute ethanol-induced liver damage in mice. 1262 62

A retrospective study was performed to (1) characterize the clinical and histologic features of those with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) values, (2) compare the spectrum of NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of NAFLD between those with a low normal versus high normal ALT value. A total of 51 subjects with NAFLD and normal ALT were identified and compared with 50 consecutive subjects with NAFLD and elevated ALT. The major indications for liver biopsy in those with normal ALT were unexplained hepatomegaly (n = 21) and evaluation as a potential donor for living donor liver transplantation (n = 16). The 2 groups were comparable with respect to age, gender distribution, and ethnicity. Approximately 80% of cases in both groups had at least 1 feature of the metabolic syndrome, the major risk factor for NAFLD. The 2 groups were also comparable with respect to the grade of the individual histologic parameters of NAFLD. A total of 12 subjects with normal ALT levels had bridging fibrosis, whereas 6 had cirrhosis. Diabetes was the only factor independently associated with an increased risk of advanced fibrosis (bridging fibrosis or cirrhosis) by multivariate analysis (relative risk: 2.3, P <.01). The mean steatosis (1.6 vs. 2.16, P <.04) and perisinusoidal fibrosis scores (0.35 vs. 0.9, P <.049) were lower in those with low normal (<30 IU/L) ALT versus high normal ALT. However, the prevalence of advanced fibrosis was similar (5 of 15 vs. 13 of 36, respectively). In conclusion, (1) the entire histologic spectrum of NAFLD can be seen in individuals with normal ALT values, (2) the histologic spectrum in these individuals is not significantly different from those with elevated ALT levels, and (3) a low normal ALT value does not guarantee freedom from underlying steatohepatitis with advanced fibrosis.
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PMID:Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. 1505 21

In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean ( +/- SEM) serum levels of ALT, AST and gamma-GT was observed only in the treated group (ALT = 81.2 +/- 9.7, 44.8 +/- 7.7, 48.1 +/- 7.7 and 52.2 +/- 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 +/- 9.8, 54.5 +/- 7, 60 +/- 7.6 and 43.7 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 +/- 4.2 Hounsfield units (HU) at the beginning versus 51.1 +/- 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content.
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PMID:A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid. 1279 1

Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown. We analyzed data on adults ages 17 yr and older (N = 15,676) from the Third National Health and Nutrition Examination Survey (1988-1994). Participants were classified as having elevated aminotransferase levels if either aspartate aminotransferase or alanine aminotransferase was elevated above normal. Aminotransferase elevation was classified as "explained" if there was laboratory evidence of hepatitis B or C infection, iron overload, or if there was a history of alcohol consumption. Analyses were weighted to provide national estimates. The prevalence of aminotransferase elevation in the United States was 7.9%. Aminotransferase elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection and high transferrin saturation were found in only 31.0% of cases. Aminotransferase elevation was unexplained in the majority (69.0%). In both men and women, unexplained aminotransferase elevation was significantly associated with higher body mass index, waist circumference, triglycerides, fasting insulin, and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05). Aminotransferase elevation was common in the United States, and the majority could not be unexplained by alcohol consumption, viral hepatitis or hemochromatosis. Unexplained aminotransferase elevation was strongly associated with adiposity and other features of the metabolic syndrome, and thus may represent nonalcoholic fatty liver disease.
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PMID:The prevalence and etiology of elevated aminotransferase levels in the United States. 1280 14

Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.
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PMID:The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. 1284 63

The fatty liver Shionogi (FLS) mouse is an inbred strain that develops spontaneous fatty liver (hepatic steatosis) chronically without obesity. Here, we reported that the mice develop spontaneous hepatocellular tumors with high incidences. The mice with age of over 1 year frequently developed whitish protuberant nodules in the livers, which were histologically diagnosed as hepatocellular adenoma and/or carcinoma (HCC). An incidence of HCC was 12/30 (40%) in males at 15-16 months of age, while in females that was 0/36 at 13-16 months and 4/42 (9.5%) at 20-24 months. Furthermore, histological examinations showed that after 2-4 months of age mononuclear cell infiltration and clusters of foamy cells appear in the fatty liver with elevated serum alanine aminotransferase, suggesting presence of inflammatory responses and liver injury. These observations show that the FLS mice develop hepatocellular tumors following steatohepatitis. The mouse might be a good animal model for investigating liver tumor and non-alcoholic steatohepatitis.
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PMID:Spontaneous development of hepatocellular carcinomas in the FLS mice with hereditary fatty liver. 1286 Feb 88

Familial hypobetalipoproteinemia (FHBL) is a rare codominant disorder of lipoprotein metabolism characterized by low levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B. Heterozygotes for FHBL have less-than-half normal LDL-cholesterol and apoB concentrations, whereas homozygotes have extremely low or undetectable LDL-cholesterol and apoB levels. These reductions in LDL-cholesterol and apoB have been suggested to provide FHBL subjects with resistance to atherosclerosis. FHBL can be caused by mutations in the APOB gene on chromosome 2. We present four novel mutations and one previously described mutation in APOB causing FHBL in five families. Immunoblotting and DNA sequencing were used to characterize the novel mutation apoB-40.3 (c.5564_5565insC) and the previously reported mutation apoB-80.5 (c.11040T>G). The apoB-6.9 (c.1018_1025del) and apoB-25.8 (c.3600T>A) mutations were identified by DNA sequence analysis, as variants shorter than apoB-31 are not detectable in plasma. A fifth mutation, the splice variant c.82+1G>A, was identified by sequencing and was found in a homozygous subject. In approximately 50% of the FHBL subjects, plasma alanine aminotransferase concentrations were mildly increased, suggestive of fatty liver. All affected FHBL subjects had low to low-normal serum vitamin E concentrations, highlighting the important and recognized relationship between lipid and vitamin E concentrations.
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PMID:Four novel mutations in APOB causing heterozygous and homozygous familial hypobetalipoproteinemia. 1287 64


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