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PubMed1996

Liver fatty acid-binding protein expression in transfected fibroblasts stimulates fatty acid uptake and metabolism.

The role of cytosolic liver fatty acid binding protein (L-FABP) in fatty acid uptake and metabolism was examined using cultured L-cell fibroblasts transfected with the cDNA encoding for L-FABP. [3H]Oleic acid was used to determine the effects of intracellular esterification on fatty acid uptake and to determine esterified fatty acid localization to specific lipid classes. cis-Parinaric acid, a poorly esterified fatty acid, was used to determine uptake in the absence of any appreciable esterification. High-expression L-cells had a 80% and 50% greater initial uptake rate for both [3H]oleic acid and cis-parinaric acid, respectively compared to low-expression L-cells. Maximal uptake of [3H]oleic acid did not plateau because of intracellular esterification. In high-expressing cells, maximal cis-parinaric acid uptake rapidly plateaued at a level 34% higher than in low-expression cells. After 1 min of incubation, the majority of cellular [3H]oleic acid was unesterified, with the bulk of the esterified portion preferentially localized to phospholipids. After 5 and 30 min, cells expressing L-FABP esterified a significantly greater amount of [3H]oleic acid into both the neutral lipid and phospholipid fractions than did low-expression cells. L-FABP expression also selectively stimulated [3H]oleic acid incorporation into choline glycerophospholipids. Thus, L-FABP expression not only stimulated fatty acid uptake at all time points, but also stimulated intracellular esterification into specific lipid pools. These results show in detail for the first time using an intact cell culture system that L-FABP expression not only stimulated fatty acid uptake, but also increased intracellular esterification of exogenously supplied fatty acids.

Animals↗
PubMed2004

Clinical aspects of fatty liver disease.

The global emergence of obesity as an epidemic has made fatty liver disease a public health problem in the Western world. The increased incidence of obesity has been paralleled by an increase in metabolic syndrome in the same cohort of patients. The net consequence of insulin resistance in a large majority of these obese individuals is hepatic steatosis, which over time in a proportion of these patients progresses to steatohepatitis and cirrhosis. Despite the increased awareness among physicians regarding its presence, the diagnostic process has been hampered by the lack of sensitive and specific population-based screening tests. Liver biopsy remains the gold standard for diagnosis as well as for grading and staging of the disease process but its precise role in the diagnostic conundrum continues to be debated.

Acyclovir↗
PubMed2006

Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD. AIM: To evaluate a multifactorial intervention in the treatment of NAFLD. METHODS: A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin-angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study. RESULTS: At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher (p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects. CONCLUSIONS: Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).

Anti-Obesity Agents↗
PubMed1989

Interaction of hemopexin, albumin and liver fatty acid-binding protein with protoporphyrin.

Equilibrium constants for the binding of protoporphyrin to serum albumin and hemopexin and liver cytosolic fatty acid-binding protein of the rat were determined fluorometrically. The experimental equilibrium constant [10(6) M-1 (mean +/- S.D.)] values were 8.4 +/- 1.3, 10.0 +/- 2.4 and 34.0 +/- 3.0 for albumin, hemopexin and liver fatty acid-binding protein, respectively. Statistical analysis showed the equilibrium constant of binding of protoporphyrin to liver fatty acid-binding protein to be significantly (p less than 0.01) higher than that to albumin and hemopexin. The data suggest that in patients with erythropoietic protoporphyria an equilibrium gradient may exist which favors the uptake by hepatocytes of plasma protoporphyrin as a result of its greater affinity for intracellular liver fatty acid-binding protein.

Animals↗
PubMed1977

Acute fatty liver of pregnancy with survival of mother and child: a case report.

A case of acute fatty liver of pregnancy (obstetric acute yellow atrophy or acute fatty metamorphosis of the liver) is reported in which cesarean section was made and both mother and child survived. The authors suggest that the prognosis was improved by rapid termination of pregnancy. The course of the disease, differential diagnosis, treatment and prognosis are discussed.

Acute Disease↗
PubMed1989

Lack of correlation between the sulfobromophthalein test and fatty liver in diabetic dogs.

The present study was performed to evaluate the correlation between fatty liver and liver function in diabetic dogs. Experimental diabetes was induced in 14 dogs by total pancreatectomy or by alloxan administration, and partial (30%) hepatectomy was performed. Diabetic dogs were compared with control dogs (N = 7) subjected only to partial hepatectomy (30%). Control and diabetic dogs were submitted to the sulfobromophthalein (BSP) liver function test. Serum BSP retention was increased in diabetic dogs but there was no correlation with the extent of fatty infiltration of the liver.

Animals↗
PubMed2006

[Fatty liver in pregnancy. A report of two cases and medical literature review].

Acute fatty liver of pregnancy is an uncommon and potentially fatal disorder usually found in the third trimester of pregnancy and the early days postpartum. It is characterized by a micro vesicular stheatosis of the liver, which is reversible with complete regression of the disease. We present two clinical cases, in the first one the patient developed encephalopathy and hypoglycemia in her third day post cesarean section; the patient underwent surgical exploration because of a subaponeurotic hematoma and the diagnosis was confirmed by liver biopsy. The patient presented spontaneous resolution of the disease and was discharged home on her 21st day after delivery. The second case was a patient on her 37th week of pregnancy that arrived to the emergency room complaining of malaise, nausea and vomit, her laboratory analyses were remarkable hypoglycemia and hyperbilirubinemia. She underwent elective pregnancy termination with a favorable maternal and fetal outcome towards spontaneous resolution. It is critical to diagnose and treat this disease in a expedite manner in order to have a favorable maternal and fetal outcome. The mortality rate has decreased dramatically from 80% in 1965 to 100% survival in 1999 according to the latest reviews. This regression of the symptoms and signs along with normalization of the laboratory values has driven some authors to call this disease as the "reversible peripartum liver failure".

Adult↗
PubMed1979

[The syndrome of acute fatty liver in pregnancy].

It is reported on the syndrome of the acute fatty liver of pregnancy and pointed out that early diagnosis, subsequent early termination of pregnancy and intensive treatment of complications, especially of hepatic and renal failure and disturbed blood clotting could reduce the mortality from almost 90 to 45 per cent within the recent years.

Acute Disease↗
PubMed1978

Idiopathic fatty liver of pregnancy with maternal and fetal survival.

A case of idiopathic fatty liver of pregnancy with survival of mother and child is reported. The management of this condition is essentially supportive; coagulation disturbances may require special attention. Maternal survival should be the major consideration and is favourably influenced by early delivery. Fetal monitoring aids obstetric management and may indirectly improve fetal survival. Evidence from the literature suggests that the condition does not usually recur in subsequent pregnancies.

Adult↗
PubMed2003

Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates.

Eighty-four consecutive subjects with nonalcoholic fatty liver disease (NAFLD) were tested for non-organ-specific autoantibodies (NOSA) by indirect immunoflorescence. Indices of insulin resistance and biochemical and anthropometric parameters were assessed. The overall prevalence of anti-nuclear-antibodies (ANA), smooth muscle antibodies (SMA) and anti-mitochondrial-antibodies (AMA) was 35.7% (30/84), 18 subjects (21.4%) being positive for ANA, 4 (4.7%) for SMA, 6 for ANA and SMA, and 2 for AMA. NOSA-positive subjects were older (P < 0.01) and mostly females (63.3%). No significant difference was found in the age-corrected parameters studied, except for copper and ceruloplasmin, which was more elevated in NOSA-positive patients. The subset of high titer (>1:100) ANA-positive patients had significantly (P < 0.05) greater insulin resistance than ANA-negative patients. In contrast, SMA-positive patients had higher gammaglobulin and significantly lower insulin resistance as compared to high-titer ANA-positive patients. In 3 NOSA-positive but not in NOSA-negative patients, liver biopsy disclosed features of overlapping NASH with autoimmune hepatitis, partially responding to diet combined with steroid treatment. In conclusion, NOSA positivity in NAFLD is more prevalent than in the general population. High-titre ANA but not SMA positivity is associated with insulin resistance.

Adult↗
PubMed1971

Mechanism of fatty liver development and hyperlipemia in rats treated with allylisopropylacetamide.

Treatment of rats with allylisopropylacetamide results in two related effects that occur sequentially. After one injection, serum FFA concentration increases and fatty liver develops without any decrease in lipoprotein synthesis. With repeated administration of the drug, fatty acid mobilization continues and acetate incorporation into lipids increases. However, fatty liver disappears with a concomitant increase in lipoprotein synthesis, resulting in hyperlipemia. It is postulated that accumulation of the liver lipid might be a regulating factor in the synthesis and transport of lipoproteins.

Acetates↗
PubMed1983

Acute fatty liver of pregnancy--survival despite associated severe preeclampsia, coma and coagulopathy.

Acute fatty liver of pregnancy is the least common and most serious cause of jaundice of pregnancy. It is rare, fewer than 100 cases having been reported (Koff, 1981). There is a high probability that it is frequently misdiagnosed and categorized vaguely as some form of variant of 'toxaemia of pregnancy' which is not surprising because of its late-pregnancy onset and the production of multi-system manifestations (Holzback, 1976). In the case reported here, there was associated severe preeclampsia with fetal intrauterine death but maternal survival.

Adult↗
PubMed2005

Sonographic measurement of the thickness of subcutaneous tissues in nonalcoholic fatty liver disease versus other chronic liver diseases.

PURPOSE: To measure an average subcutaneous tissue thickness in nonalcoholic fatty liver disease (NAFLD) and other liver diseases using bedside sonography and make comparisons of thickness between groups. The study also addressed whether a cut-off subcutaneous tissue thickness exists below which NAFLD is unlikely. METHODS: Sonograph was performed on 113 consecutive patients with chronic liver disease. Diagnosis was derived from serological data combined with liver biopsy in all cases. Distance was measured between the skin and the liver surface and was labeled the subcutaneous tissue thickness. RESULTS: Of the 113 patients, 16 were diagnosed with NAFLD, 56 were diagnosed with chronic hepatitis C, 17 were diagnosed with autoimmune liver disease, and 24 had miscellaneous diagnoses (hepatitis B, hemochromatosis, granulomatous hepatitis, and cryptogenic hepatitis). The subcutaneous tissue thickness was 25.6 mm +/- 5.6 mm in NAFLD versus 19.5 mm +/- 5.2 in the non-NAFLD patients (p < 0.001). The subcutaneous tissue thickness of the HCV group was 20.2 mm +/- 4.8, and although it was not different than all other patients, it was different from the NAFLD patients (p < 0.01). Fifteen out of sixteen of the NAFLD patients had a greater than average subcutaneous tissue thickness (20 mm). CONCLUSIONS: A sonographically measured subcutaneous tissue thickness of less than 20 mm makes the diagnosis of NAFLD unlikely.

Body Mass Index↗
PubMed1987

Acute fatty liver of pregnancy. A reassessment based on observations in nine patients.

Acute fatty liver of pregnancy was diagnosed in nine patients over a 10-year period. Eight patients had severe hepatic dysfunction typical for this syndrome and one had subclinical disease but typical hepatic histologic findings. All patients survived with little fetal wastage; all had preeclampsia. Histologic findings included cholestasis, hepatocellular necrosis, and inflammation, as well as microvesicular fat. Histologic findings from biopsy specimens of four of seven patients were initially misinterpreted as hepatitis. This disorder may have both a broad clinical and histologic spectrum; it is probably not rare but often misdiagnosed, perhaps as viral hepatitis. The concurrence of this disorder with toxemia of pregnancy suggests that these entities may be pathophysiologically related.

Acute Disease↗
PubMed1989

[Acute pregnancy fatty liver with survival of the mother and child].

A case of acute fatty liver as a rare cause of pregnancy-induced jaundice is reported. Near term the 25-year-old patient became rapidly jaundiced. On admission laboratory tests showed signs of incipient coagulopathy and impaired renal function. When fetal vital signs deteriorated cesarean section was performed. After surgery the fullblown picture of disseminated intravascular coagulation developed, with profuse bleeding only controllable by rigorous substitution of plasma factors. Acute hepatic insufficiency with ascites followed. Despite the marked bilirubin elevation the hepatic enzymes were only slightly raised. In addition, acute renal insufficiency, pancreatitis and hyperuricemia developed. Under intensive care the patient recovered slowly and was discharged after 4 weeks with a healthy baby.

Adult↗
PubMed1999

A case-control study of fatty liver disease and organic solvent exposure.

BACKGROUND: Clinical experience of cases of fatty liver disease (FLD) with exposure to organic solvents suggested a possible risk. METHODS: Thirty male cases of FLD, ages 20-59 years, with biopsy records at departments of pathology in southeast Sweden were compared to 120 male controls randomly drawn from the study area population. Questionnaire information was obtained about job titles and specific occupational exposures; exposure level categories were then assessed blindly for both cases and controls. Medical records for cases were scrutinized to elucidate possible confounding and/or interacting effects from alcohol, the use of drugs, and other diseases. RESULTS: Moderately intense and mixed solvent exposure for more than 1 year within the last 15 years prior to diagnosis resulted in an age-adjusted Mantel-Haenszel odds ratio of 4.3 (95% confidence interval (CI), 1.2-15); for intense exposure, the odds ratio was 7.7 (95% CI 1.7-48). Confounding from alcohol, use of drugs, other diseases, and overweight could be ruled out with reasonable confidence. CONCLUSIONS: This study indicates that occupational exposure to organic solvents may play a role in the development of FLD, as indicated earlier in case reports and in one small case-control study.

Adult↗