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PubMed2004

[Imaging diagnosis for fatty liver: a systematic review].

OBJECTIVE: To systematically assess imaging diagnostic tests for fatty liver and provide a decision-making basis for clinical diagnosis and screening. METHODS: Electronic searches were conducted on the Chinese Biomedical Database, PubMed, and EMBASE, combining with manually searching of Chinese literature. All searches were completed until November 2002. All studies which evaluated imaging diagnostic test of human fatty liver were included. Data of diagnostic accuracy in the included studies were extracted, and methodological quality of the studies was assessed independently by two reviewers according to the established quality standard. Quantitative analysis or qualitative description were performed based on available data. RESULTS: Of 13 studies that met the eligibility criteria, 10 studies evaluated the diagnostic accuracy of B-mode ultrasound, 3 studies evaluated contrast-enhanced (helical) CT. To assess 7 diagnostic test studies for fatty liver that used liver biopsy as reference test: the pooled sensitivity of B-mode ultrasound was 0.89 (95% confidence interval 0.87-0.92), specificity was 0.94 (95% confidence interval 0.92-0.96) and the Q value was 0.90 by adjusted SROC method. To assess 2 diagnostic test studies for fatty liver that used CT as reference test: the pooled sensitivity, specificity, and Q value were 0.92 (95% confidence interval 0.89-0.96), 0.88 (95% confidence interval 0.84-0.92), and 0.90 respectively by adjusted SROC method. CONCLUSIONS: B-mode ultrasound method can be regarded as an effective method for fatty liver diagnosis and screening. The methodologic quality of diagnostic test needs to be improved.

Fatty Liver↗
PubMedDate not supplied

SPIO-enhanced MR imaging of focal fatty liver lesions.

BACKGROUND: The purpose of this study was to assess the features of focal fatty liver lesions with superparamagnetic iron oxides (SPIO) on magnetic resonance (MR) images. METHODS: We retrospectively studied five patients with six histologically proven focal fatty liver lesions who had been examined by MR with use of SPIO. The features of the focal fatty liver lesions on two T2-weighted post-SPIO-enhanced MR images, T2*-weighted fast low-angle shot (FLASH) sequences, and T2-weighted turbo-spin echo (TSE) sequences were analyzed, and the percentages of signal intensity loss of the lesions and normal liver parenchyma were calculated. RESULTS: All the fatty liver lesions exhibited different degrees of SPIO uptake, which were presented by a distinct loss of signal intensity on both post-SPIO-enhanced T2-weighted sequences. The percentage of signal intensity loss of the lesions on SPIO-enhanced images was higher than that of normal liver parenchyma in all the cases. CONCLUSION: Focal fatty liver lesions exhibit a high uptake of SPIO. The uptake is higher than that of the normal liver.

Adult↗
PubMed2001

Correlation between fatty liver and coronary risk factors: a population study of elderly men and women in Nagasaki, Japan.

The relation between fatty liver, detected by ultrasonography as a marker of visceral fat accumulation, and coronary risk factors was studied in 810 elderly men and 1,273 elderly women in Nagasaki, Japan from 1990 to 1992. The prevalence of fatty liver was 3.3% in the male and 3.8% in the female non-obese participants (BMI, body mass index < 26.0 kg/m2) and 21.6% in the male and 18.8% in the female obese participants (26.0 kg/m2 < or = BMI). Fatty liver was significantly (p < 0.01) related to hypercholesterolemia and hypertriglyceridemia in the men and to hypertension, hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and diabetes mellitus or impaired glucose tolerance (DM+IGT) in the women independent of age, obesity, smoking and drinking. Non-obesity with fatty liver, rather than obesity with or without fatty liver, had the highest odds ratio for hypertension and low-HDL cholesterol in the men and for hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and DM+IGT in the women. The prevalence of fatty liver is the same in elderly men and women, and fatty liver is an independent correlate of coronary risk factors in the elderly.

Aged↗
PubMedDate not supplied

Focal fatty liver sparing lesion presenting as a "pseudotumour": case report.

We are reporting our experience of a case of "focal fatty liver sparing lesion" in a 24-year-old patient, without any evident predisposing factors for fatty infiltration of the liver. Fatty liver infiltration was sparing the posterior part of liver segment VI, defining an area which was mimicking a lesion on US and CT. Fatty liver infiltration is usually diffuse but may be patchy or localized. Occasionally, focal areas of normal parenchyma in an otherwise diffuse fatty liver may simulate mass lesions. Typically, these "pseudolesions" appear as echo-poor areas against a background of bright echoes due to fatty infiltration and may pose a difficult diagnostic problem. We present this case and discuss the investigation process in order to differentiate this lesion from a hepatic tumor.

Adult↗
PubMed1997

The relationship between fatty liver and hyperinsulinemia in obese Japanese children.

BACKGROUND: Previous reports have revealed that fatty liver involving obesity is closely related to insulin resistance or hyperinsulinemia in adulthood. This study investigates the importance of hyperinsulinemia in obese children with fatty liver. METHODS: The subjects were 228 obese children 6 to 15 years old in Niigata Prefecture, Japan. The serum level of glutamic pyruvic transaminase (GPT) was evaluated as an indicator of fatty liver. The effects of their percent obesity (percent over ideal body weight), Rohrer index (g/cm3), skinfold thickness, percent body fat measured by bioelectrical impedance analysis, total cholesterol (TC), high-density lipoprotein cholesterol, triglyceride (TG), blood glucose, and immuno-reactive insulin (IRI) on GPT were evaluated using regression analyses. RESULTS: The incidence of fatty liver (GPT over 35 IU/I) was 24.1% in this study. In simple regression analyses, percent obesity, Rohrer index, skinfold thickness, TC, TG, blood glucose, and IRI correlated positively with GPT (p < 0.05). In stepwise regression analysis including these seven variables, the predictive equation for GPT as a function of IRI alone accounted for 24.2% of the total variance of GPT. The addition of TC alone, and TC and percent obesity together increased the coefficients of determination to 28.4% and 29.9%, respectively. Rohrer index, skinfold thickness, Tg, and blood glucose were not taken as related variables with GPT. CONCLUSION: Hyperinsulinemia is an important contributor to the development of fatty liver, apparently more than anthropometric data, blood glucose, or serum lipids in childhood obesity.

Adolescent↗
PubMed2005

Increase in liver antioxidant enzyme activities in non-alcoholic fatty liver disease.

AIMS: Steatosis may increase oxidative stress, which is counteracted by cellular enzymatic (cytosolic and mitochondrial superoxide dismutases (Cu/Zn-SOD and Mn-SOD), glutathione peroxidase (GPx), catalase) and non-enzymatic antioxidant systems. We aimed to determine, in patients with non-alcoholic fatty liver disease (NAFLD), the level of antioxidant defenses (1) in liver biopsies, to demonstrate the existence of oxidative stress; (2) in erythrocytes and plasma, to determine whether their antioxidant defenses reflect liver oxidative stress. METHODS: Erythrocyte and plasma antioxidant defenses were prospectively studied in two groups of 16 patients: patients with NAFLD and controls. Liver biopsies were performed in eight NAFLD patients; liver antioxidant enzyme activities were measured and compared with those in 12 control livers used for transplantation. RESULTS: Cu/Zn-SOD, GPx and catalase activities were significantly higher in NAFLD livers than in controls whereas no significant differences were observed in Mn-SOD activity, and thiobarbituric acid-reactive substance (TBARS) concentration. No differences were observed in erythrocyte antioxidant enzyme activities (GPx, catalase, Cu/Zn-SOD), erythrocyte TBARS concentration, and plasma alpha-tocopherol concentration. CONCLUSIONS: Liver antioxidant enzyme activities were high in patients with NAFLD, reflecting an oxidative stress possibly involved in inflammation and fibrogenesis. However, erythrocyte and plasma antioxidant defenses did not reflect intrahepatic peroxidation.

Adult↗
PubMed2006

Associations between liver histology and cortisol secretion in subjects with nonalcoholic fatty liver disease.

OBJECTIVES: To assess associations between the activity of hypothalamo-pituitary-adrenal (HPA) axis and liver histology in patients with nonalcoholic fatty liver disease (NAFLD). DESIGN AND PATIENTS: In a cross-sectional study, we enrolled 50 consecutive, overweight, NAFLD patients and 40 control subjects who were comparable for age, sex and body mass index (BMI). MEASUREMENTS: NAFLD (by liver biopsy), HPA axis activity (by 24-hour urinary free cortisol [UFC] excretion and serum cortisol levels after 1 mg dexamethasone), insulin resistance (by homeostasis model assessment: HOMA-IR), and metabolic syndrome (MetS) features. RESULTS: NAFLD patients had markedly higher (P < 0.001) 24-h UFC (149 +/- 24 vs. 90 +/- 16 nmol/day) and postdex suppression cortisol concentrations (32 +/- 10 vs. 16 +/- 7 nmol/l) than controls. The MetS and its individual components were more frequent among NAFLD patients. The marked differences in urinary/serum cortisol concentrations that were observed between the groups were little affected by adjustment for age, sex, BMI, waist circumference, systolic blood pressure, triglycerides, homeostasis model assessment for insulin resistance score and presence of diabetes. Importantly, 24-h UFC and postdex cortisol concentrations strongly correlated to hepatic necroinflammatory grade (P < 0.01) and fibrosis stage (P < 0.001) among NAFLD patients. By logistic regression analysis, 24-h UFC (odds ratio (OR) 1.80, 95%CI 1.3-2.8) or postdex cortisol concentrations (OR 1.95, 95%CI 1.4-3.1) independently predicted the severity of hepatic fibrosis, but not necroinflammation, after adjustment for potential confounders. CONCLUSIONS: These results suggest that NAFLD patients have a subtle, chronic overactivity in the HPA axis (that is closely associated with the severity of liver histopathology) leading to subclinical hypercortisolism that might be implicated in the development of NAFLD.

Age Factors↗
PubMed1989

Fatty acid interactions with rat intestinal and liver fatty acid-binding proteins expressed in Escherichia coli. A comparative 13C NMR study.

Enterocytes in the small intestinal mucosa contain abundant quantities of two homologous cytosolic proteins known as intestinal and liver fatty acid-binding proteins (I- and L-FABP, respectively). To elucidate structure-function relationships for these proteins, the interactions between 13C-enriched palmitate and oleate and Escherichia coli-expressed rat I- and L-FABP were systematically compared using 13C NMR spectroscopy. NMR spectra of samples containing fatty acids (FA) and I-FABP at different molar ratios (all at pH 7.2 and 37 degrees C) exhibited a single carboxyl resonance corresponding to FA bound to I-FABP (181.4 ppm, peak I) and an additional carboxyl resonance corresponding to unbound FA in a bilayer phase (179.6 ppm). Peak I reached a maximum intensity corresponding to 1 mol of bound FA/mol of I-FABP under all sample conditions examined. NMR spectra for samples containing FA and L-FABP also exhibited a single carboxyl resonance corresponding to FA bound to L-FABP but at a different chemical shift value (182.2 ppm, peak L). Its maximum intensity varied depending on the physical state of the unbound FA (liquid crystalline or crystalline), the FA used (palmitate or oleate), and the sample pH. In the presence of a liquid crystalline (bilayer) phase, up to 1 (oleate) or 2 (palmitate) mol of FA were bound/mol of L-FABP, but in the presence of a crystalline phase (1:1 acid-soap), up to 3 mol of palmitate were bound/mol of L-FABP (all at pH 7.2). Peak I exhibited little or no ionization shift over a wide pH range (pH 3.0-11.0), and its chemical shift was unaffected by the ionization of Lys and His residues. Hence, the carboxylate group of FA bound to I-FABP was solvent inaccessible and most likely involved in an ion-pair electrostatic interaction with the delta-guanidinium moiety of an Arg residue. In contrast, peak L exhibited an ionization shift and an estimated apparent pKa value similar to that obtained for monomeric FA in water, suggesting that the carboxylate groups of FA bound to L-FABP were solvent accessible and located at or near the protein solvent interface. With decreasing pH, FA dissociated from L-FABP but not I-FABP, as monitored by NMR peak intensities. Concurrently, a large decrease in circular dichroism molar ellipticity was observed with L-FABP but not I-FABP. In conclusion, I-FABP and L-FABP are distinct with regards to their FA-binding stoichiometries, binding mechanisms, and sensitivity to pH.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Prevalence of fatty liver in a general population of Okinawa, Japan.

A total of 2,574 residents in Yaeyama District of Okinawa, Japan, were investigated using real time ultrasonography to determine the real prevalence of fatty liver in the general population and to define its associated factors. Overall prevalence of fatty liver was 14.0%. Prevalence of fatty liver in persons under 19 years old was only 1.2%, and increased with age to a maximum in persons 40-49 years of age and then decreased. For persons over 20 years old, obesity index and serum levels of triglyceride and total cholesterol were measured, and alcohol consumption was asked. Prevalence of fatty liver was significantly higher in drinkers than non-drinkers (p less than 0.01), and increased with alcohol consumption. Furthermore, in persons not suffering from obesity prevalence of fatty liver was significantly higher in drinkers than in non-drinkers (p less than 0.001). The results of logistic regression analysis indicated that obesity and elevated serum triglyceride level in both sexes, and alcohol in males were significant predictors of fatty liver. In conclusion, prevalence of fatty liver increased with age to a maximum in persons 40-49 years of age and overall was 14.0%. Obesity was the strongest associated factor in both sexes and in males alcohol was also a strong factor.

Age Factors↗
PubMed2006

Differential liver sensitization to toll-like receptor pathways in mice with alcoholic fatty liver.

Gut-derived, endotoxin-mediated hepatocellular damage has been postulated to play a crucial role in the pathogenesis of alcohol-induced liver injury in rodents. Endotoxins induce production of tumor necrosis factor alpha (TNF-alpha) by Kupffer cells via Toll-like receptor (TLR) 4 and contribute to liver injury. This study addressed the contribution of other TLRs and ligands to alcoholic fatty liver. C57Bl6/J mice were fed a modified Lieber-DeCarli diet. Serum aminotransferase measurements, histological analysis, and quantification of liver TNF-alpha and TLR1-9 messenger RNA (mRNA) were performed. The effect of TLR ligands on liver injury was assessed in vivo. Neomycin and metronidazole or diphenyleneiodonium sulfate (DPI) were administered to evaluate the role of gut bacteria and NADPH oxidase activity, respectively, in hepatic TLR expression. Enteral ethanol (EtOH) exposure induced steatosis and increased liver weight, aminotransferase levels, and expression of TLR1, 2, 4, 6, 7, 8, and 9 liver mRNA. Injection of lipoteichoic acid, peptidoglycan (PGN), lipopolysaccharide (LPS), loxoribine, and oligonudeotide containing CpG (ISS-ODN) increased TNF-alpha mRNA expression more in the livers of EtOH-fed mice than in control mice. PGN, LPS, flagellin, and ISS-ODN induced liver inflammatory infiltrate in EtOH-fed mice but not control mice. Addition of antibiotics reduced the severity of alcoholic fatty liver without affecting TLR expression, whereas daily DPI injections reduced the EtOH-mediated upregulation of TLR2, 4, 6, and 9 mRNA. In conclusion, EtOH-fed mice exhibited an oxidative stress dependent on upregulation of multiple TLRs in the liver and are sensitive to liver inflammation induced by multiple bacterial products recognized by TLRs.

Animals↗
PubMed1992

An in vitro reversible interconversion of rat liver fatty acid binding protein having different isoelectric points by virtue of the fatty acid content.

Rat liver fatty acid binding protein (FABP) was purified to homogeneity by procedures including Sephadex G-100 and DEAE-cellulose column chromatographies. FABP was resolved into two major peaks, A and B, by the first DEAE-cellulose column chromatography. Each of these two fractions exhibited apparent homogeneity upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate with a molecular weight of 14,000 Da and amino acid analysis of these fractions has revealed that they are virtually identical or closely resemble each other. However, their fatty acid content was significantly different and heterogeneity was clearly demonstrated in the patterns of isoelectric focusing. In this communication, a single isoform (pI 5.0) from peak B FABP was further purified by successive DEAE-cellulose column chromatography and used as the final preparation. When the final FABP was partly freed of fatty acids by a mild delipidation technique using Lipidex 1,000, the pI shifted upward from 5.0 to 7.0. However, the pI of the delipidated FABP returned to its original pI of 5.0 after recombining fatty acids. These in vitro manipulations of bound fatty acid content made clear its possible cause of the microheterogeneity of FABP.

Amino Acids↗
PubMed1988

Isolation and mapping of the beta-hydroxyacyl dehydratase activity of chicken liver fatty acid synthase.

Chicken liver fatty acid synthase is cleaved by kallikrein into polypeptides ranging in molecular weight from 10,000 to 100,000. Fractionation of the digest by ammonium sulfate and chromatography on a Matrix Red A affinity column resulted in the isolation of a polypeptide (Mr = 26,000) containing the beta-hydroxyacyl dehydratase activity, but no other partial activities normally associated with the fatty acid synthase. The specific activity of the dehydratase increased 9 to 12 times in this fraction, an increase that is within the expected range based on relative molecular weight. Kinetic parameters of the purified dehydratase toward the model substrate, crotonyl-CoA, showed no change in apparent Km values and a 12-fold increase in Vmax values as compared to dehydratase activity of the intact synthase. However, the purified fragment did not catalyze the hydration of the crotonyl-N-acetylcysteamine derivative, a substrate that is readily hydrated by the intact synthase. Antibodies against the purified 26-kDa fragment cross-react with the intact synthase and the hydratase-containing fragments produced at all stages of digestion with kallikrein or trypsin as shown by Western blot analyses. The results show that the beta-hydroxyl dehydratase activity of the fatty acid synthase is located in the reduction Domain II (Tsukamoto, Y., Wong, H., Mattick, J. S., and Wakil, S. J. (1983) J. Biol. Chem. 258, 15312-15322) of the synthase subunit.

Animals↗
PubMed1983

Obese rats develop hyperketonaemia and a fatty liver during lactation.

Lactating rats made obese before conception by feeding high energy foods show a decreased rate of lipogenesis in vivo in mammary gland, but not in liver. Obese lactating rats have an increased hepatic fat content, together with moderate increase in blood ketone bodies. It is suggested that these changes are due to mobilization during lactation of the expanded adipose tissue lipid pool in the obese rats which results in overloading the liver with fatty acids. The concomitant increase in ketone body concentrations may inhibit glucose utilization and hence lipogenesis in the lactating mammary gland of obese rats.

Animals↗
PubMed2006

[Epidemiology and natural history of primary nonalcoholic fatty liver disease].

The clinical impact of nonalcoholic fatty liver disease depends on its prevalence and natural history. The prevalence in the adult population is estimated to be about 23% and is on the increase. Thus, it has become the most common cause of persistent elevated liver enzymes, chronic liver disease, and cryptogenic cirrhosis in developed countries. The increasing prevalence of nonalcoholic fatty liver disease, which is approaching epidemic proportions, is parallel to that of other disorders associated with insulin resistance, especially obesity and type 2 diabetes mellitus. This entity occurs in men and women equally and in all age groups. The natural history is poorly defined mainly due to the scarcity of histologic follow-up studies. Although steatosis alone has a more benign clinical course, steatohepatitis is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in a similar way to other causes of chronic liver diseases. Progression seems to be mainly dependent on the severity of histological damage at diagnosis, but age older than 40 years, obesity, and type 2 diabetes have also been associated with an increased risk of liver fibrosis and progression to cirrhosis.

Fatty Liver↗
PubMed1980

Incidence and severity of fatty liver in dairy cows.

A survey of the incidence and severity of post-parturient fatty liver in high yielding dairy cows was carried out on 151 cows and 46 heifers from four Friesian herds and one Guernsey herd. In Friesian and Guernsey cows from the second lactation onwards fat occupied a significant proportion (15 to 32 per cent) of the hepatic parenchyma at one week after calving but decreased to low values at eight weeks after calving. Fatty liver was insignificant in heifers of either breed. When the fatty liver was classified according to the amount of fat at one week after calving, 66 per cent of Friesian cows and 33 per cent of Guernsey cows had a moderate or severe fatty liver. The severity of the fatty liver was related to the loss of condition score after calving but not the condition score at calving.

Animals↗