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[Acute fatty liver of pregnancy. Report of a case and review of the literature].

Acute Fatty Liver of Pregnancy. The acute fatty liver of pregnancy (AFLP) is an uncommon entity, potentially fatal, which affects women during the last quarter of pregnancy. It is characterized by a prodromic period of symptoms followed by jaundice, hepatic failure, clotting disorders and fatty infiltration of the liver, evident through hepatic biopsy. The incidence ranks from 1 to 20 thousand births, and it is more frequent among women with multiple pregnancies. We report the case of a 29-year-old patient, with multiple pregnancy 33 to 34 weeks of gestation, blood pressure values of 140/90 mmHg, 160,000/dL platelets, PT 25.6 seconds, TPT 64.7 seconds, blood glucose 52 mL/dL, creatinine 2.1 mg/dL, uric acid 11.9 mg/dL, lactic dihydrogenase 1063 U/l, GPT 220 U/l, AF 1172 U/l, total bilirubin 8.4 mg/dL, proteinuria 30 mg/dL. A cesarean section was practiced after correcting the coagulation disorders. The first twin was a male with birth weight of 2,070 g, APGAR 8-9; the second twin was a female fetal death weighting 2,050 g. Hepatic biopsy confirmed the diagnosis. The cause of AFLP is unknown. The frequency among multiple pregnancies is higher. Almost half of the cases have hypertension and proteinuria. There are also high levels of both transaminases, phosphatase and bilirubins and hypoglycemia. The prothrombin time is enlarged. The differential diagnostic between pre-eclampsia and AFLP is not crucial since the obstetric management is the same. The main treatment is promptly deliverance and general measures. The obstetrician must be aware of this hepatic disease.

Acute Disease↗

Sequential production of fatty liver, hepatitis, and cirrhosis in sub-human primates fed ethanol with adequate diets.

This study reproduces in experimental animals the sequential development of all the liver lesions seen in the human alcoholic: in 15 baboons fed ethanol, all developed fatty liver, five progressed to hepatitis, and five had cirrhosis. Maintenance of a nutritionally adequate regimen despite the intake of inebriating amounts of ethanol (50% of total calories) was achieved by incorporation of the ethanol in a totally liquid diet. Upon ethanol withdrawal, signs of physical dependence, such as seizures and tremors, developed. Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis) and differed from the alterations produced by choline and protein defiencies. At the fatty liver stage, some "adaptive" increases in activity of microsomal enzymes [aniline hydroxylase (EC 1.14.14.1) and the microsomal ethanol oxidizing system] were observed, but these tended to disappear with the development of hepatitis and cirrhosis. Fat accumulation was also much more pronounced in the animals with the hepatitis as compared with those with simple fatty liver (an 18-fold compared with 3- to 4-fold increase in liver triglycerides). The demonstration that these lesions can develop despite an adequate diet indicates that in addition to correction of the nutritional status, control of alcohol intake is mandatory for the management of patients with alcoholic liver injury.

Animals↗

Detection of alcohol-induced fatty liver by computerized tomography.

Computerized tomographic (CT) scanning of the liver was undertaken in 17 occasional and 19 heavy drinkers undergoing health screening. The median attenuation value of the liver (CT number) in occasional drinkers with normal liver function tests was 54.4 compared with 25.9 in the heavy drinkers (P less than 0.001). Fourteen of the heavy drinkers had a CT number below the lowest value observed in occasional drinkers with normal liver function, indicating reduced liver density due to fatty change. Serum gamma-glutamyl transpeptidase was normal in 36% of these individuals. A rise in CT number was observed in 4 out of 5 heavy drinkers who underwent a second scan after decreasing their alcohol consumption. These findings suggest that CT scanning provides a noninvasive and convenient method of screening for a fatty liver, which occurred to a variable degree in over 70% of the men who admitted to regularly taking 8 or more alcoholic drinks per day.

Fatty Liver, Alcoholic↗

[A study on fatty liver in health examination participants].

We investigated the condition of the liver in a total of 5486 subjects (3889 males and 1597 females) who received adult-disease screening examinations. The following results were obtained. 1. Fatty liver was found in 13.9% of the males and 3.8% of the females with a male/female ratio of about 3.7 to 1. In males, the prevalence of fatty liver was lower in those in their 20's than in any other age ranks, while there was little difference in the age range from the 30's to the 50's. In females, the prevalence sharply increased in those in their 50's. 2. The percentage of fatty liver increased with the obesity index in both males and females. 3. With respect to alcohol drinking, the prevalence of fatty liver was not affected by the presence or absence of alcohol drinking, the daily drinking quantity and total drinking quantity. 4. Of those screened for adult disease, 14.7% of the males and 2.7% of the females had abnormal liver function, with a male/female ratio of about 5.4 to 1. In both males and females, the prevalence of fatty liver was higher in those who had abnormal rather than normal liver function.

Adult↗

Relationship between pulmonary fat embolism and core body temperature in rats with a severe fatty liver.

We previously demonstrated that pulmonary fat embolism was induced by elevation of the core body temperature, in rats with a fatty liver. The aim of the present examination was to investigate the core body temperature at which pulmonary fat embolism developed capillaries through exposure to a high temperature, in rats with a fatty liver. Following heat stress, pulmonary fat embolism was observed to a slight degree at a core body temperature of 41 and 42 degrees C, whereas the severity of pulmonary fat embolism was greatly increased and was classified as severe at a core body temperature of 43 degrees C. Moreover, the concentrations of aspartate aminotransferase and alanine aminotransferase within plasma were significantly increased at a core body temperature of 43 degrees C. These results clearly indicate that the development of pulmonary fat embolism could be related to hyperthermia at above 42 degrees C following heat stress, and that fat emboli may be derived from the fatty liver itself. It is thus likely that pulmonary fat embolism can be considered as one form of evidence of hyperthermia in an individual with a fatty liver.

Animals↗

AICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats.

BACKGROUND: Previous work with metformin has shown that this antidiabetic agent improves nonalcoholic fatty liver in ob/ob mice. AMP-activated protein kinase (AMPK) is one of the major cellular regulators of lipid and glucose metabolism, and reportedly mediates the beneficial metabolic effects of metformin. In this study, we examined the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an AMPK activator, on an experimental model of ethanol-induced hepatic steatosis. METHODS: Rats were randomly divided into three groups: (A) rats fed ethanol-containing liquid diet for six weeks; (B) rats pair-fed ethanol-containing liquid diet for six weeks, during the last three weeks of which they were subcutaneously injected with 0.5 mg AICAR/g body weight per day; (C) rats pair-fed isocaloric liquid diet without ethanol for six weeks. At the end of the six-week period, the animals were sacrificed. Serum and liver specimens were analyzed using biochemical and histologic methods, as well as real-time PCR. RESULTS: Chronic ethanol feeding resulted in fatty liver both histologically and biochemically, whereas AICAR administration attenuated the degree of change in the liver. AICAR also decreased the hepatic sterol regulatory factor binding protein-1c (SREBP-1c) and reduced fatty acid synthase (FAS) expression; these changes led to reduced triglyceride synthesis in rat livers. Furthermore, detection of 4-hydroxy-2-nonenal (4-HNE)-protein adducts showed that the AICAR treatment also decreased the products of lipid peroxidation. CONCLUSION: In this preclinical rat model, AICAR, an AMPK activator, appears to protect the liver from fatty changes associated with chronic alcohol use. As such, AICAR may have a role in the treatment and prevention of alcohol-induced fatty liver.

AMP-Activated Protein Kinases↗

Inhibition of intestinal cholesterol absorption by ezetimibe is a novel therapeutic target for fatty liver.

Ezetimibe is a novel lipid-lowering agent that inhibits intestinal absorption of dietary and biliary cholesterol. The effects of ezetimibe on low-density lipoprotein (LDL)-cholesterol were found to generally consistent across all subgroups analyzed, including baseline lipid profile, hypertension, diabetes mellitus, and body mass index. Furthermore, recent clinical studies also revealed that co-administration of ezetimibe with on-going statins offered a well-tolerated and efficacious treatment to lower LDL-cholesterol levels in hypercholesterolemic patients with diabetes mellitus or the metabolic syndrome. Niemann-Pick C1 like 1 (NPC1L1) protein is recently found to be critical for intestinal cholesterol absorption, and is a target protein for ezetimibe. Human NPC1L1 protein is predominantly expressed in liver, whereas small intestine expression is only about 2-4% of that found in the liver. Thus, NPC1L1 does not function solely in the intestinal cholesterol absorption. Furthermore, loss of NPC1L1 expression has been shown to protect against diet-induced fatty liver. These observations let us to speculate that ezetimibe will become a new therapeutic approach for the treatment of non-alcoholic fatty liver, the hepatic manifestation of insulin resistant patients with the metabolic syndrome. In this paper, we would like to propose the possible ways of testing our hypothesis as follows. (1) Does ezetimibe treatment improve fatty liver in patients with hypercholesterolemia or the metabolic syndrome? If the answers are yes, are these beneficial effects of ezetimibe superior to those of other anti-hyperlipidemic resins with equihypolipidemic properties? (2) Does ezetimibe treatment improve insulin sensitivity in fatty liver patients with the metabolic syndrome? (3) How about the effects of ezetimibe treatment on serum levels of adiponectin, a key adipokine with insulin-sensitizing property? Large clinical trials will provide us with more definite information whether ezetimibe treatment can improve fatty liver and resultantly reduce the risk of progression of liver diseases in patients with the metabolic syndrome.

Adiponectin↗

Peroxisome proliferator activated receptor-gamma in pathogenesis of experimental fatty liver disease.

AIM: To study the expression of peroxisome proliferator activated receptor-gamma (PPARgamma) in the liver of rats with fatty liver disease (FLD) and to explore the role of PPARgamma in the pathogenesis of FLD to provide the basis for using PPARgamma ligand to treat patients with FLD. METHODS: Forty Wistar rats were divided into 4 groups of ten rats each randomly: normal group (group A), alcohol group (group B), fat-rich diet group (group C), alcohol and fat-rich diet group (group D). The rats were sacrificed at the end of the 16th week from the feeding day. Alanine aminotransferase (ALT), tumor necrosis factor-alfa (TNFalpha) in serum and malondialdehyde (MDA) in liver homogenate were determined; livers were collected for observing pathologic changes by HE, Sudan IV, Masson stain under microscope. The morphologic results were analyzed by picture quantitative analysis technique. The changes of ultrastructure were also examined under electron microscope. The expression of PPARgamma in liver was detected by immunohistochemistry and RT-PCR. The correlations between the expression of PPARgamma and biochemical indexes, and liver histology were analyzed. RESULTS: The steatosis, inflammation, necrosis and fibrosis were present in livers of different experimental groups, especially in livers of alcohol and fat-rich diet group. The content of immunodetectable PPARgamma was decreased remarkably in the livers of model rats (group B-D); the level in alcohol and fat-rich diet group (3.43+/-1.48) was significantly lower than that in normal group (18.34+/-3.73), alcohol group (8.82+/-2.52) and fat-rich diet group (11.73+/-2.51) (all P<0.01). The level of PPARgamma mRNA was also lower in the livers of model rats (group B-D) than in livers of controls. The expression of PPARgamma in rat liver correlated negatively with the degree of its inflammation, necrosis and fibrosis, as well as the level of serum TNFalpha and the content of MDA in liver homogenates, but not with steatosis or serum ALT. CONCLUSION: Decreased expression of PPARgamma may play an important role in the development of hepatocellular inflammation, necrosis and fibrosis of rats with FLD. Thus, activating PPARgamma by its ligand can be anticipated to provide a therapy target for FLD.

Animals↗

Pharmacokinetic changes of several antibiotics in chickens during induced fatty liver.

The concentrations of five antibiotics (erythromycin, lincomycin, penicillin G, streptomycin and oxytetracycline) were determined in chicken serum before and after induced fatty liver. The pharmacokinetic variables were calculated according to the obtained data. The crossover trial design involved 10 chickens for each antibiotic. The fatty liver was produced by oestradiol-dipropionate injections and monitored by serum malic enzyme activity determinations. Protein binding of the respective antibiotics was determined in vitro in the serum obtained from normal and oestrogen-treated birds. Induction of fatty liver caused several changes in the determined variables. The measured peak concentrations were higher for lincomycin and erythromycin and lower for penicillin and oxytetracycline while streptomycin remained unchanged. The peak concentration of streptomycin appeared earlier and the peak of oxytetracycline later than in the normal chickens. The elimination half-lives were shorter for erythromycin, lincomycin and streptomycin and increased for penicillin and oxytetracycline. The area under the concentration curve (AUC) decreased for erythromycin, penicillin and streptomycin, increased for oxytetracycline and remained unchanged for lincomycin. The body clearance (ClB/f) and the apparent specific volume of distribution (Vd(area'/f) were considerably changed in association with fatty liver induction. Since the fraction of the drug absorbed (f) is not known, it can only be speculated that changes in distribution rather than reduced liver function altered the kinetics. The protein binding was decreased for all the antibiotics, but this did not seem to be the reason for changes in kinetics, except perhaps in the case of penicillin.

Animals↗

Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): diagnosis and clinical course.

Non-alcoholic fatty liver disease (NAFLD) is a frequent syndrome encompassing fatty liver alone and steatohepatitis (NASH). Often asymptomatic, the suspicion arises because of abnormal aminotransferases or a bright liver on abdominal ultrasound. It should be suspected during evaluation of associated conditions as obesity, diabetes or dyslipidaemia. The diagnostic evaluation must exclude other potential causes of liver disease and may include a liver biopsy, the only method able to confirm features of necroinflammation and fibrosis that define NASH and its prognostic implications. Indeed, the presence of necroinflammation has been associated with a significant risk of progression to cirrhosis and eventually hepatocellular carcinoma. Age >45 years, obesity and diabetes have also been associated with an increased risk of liver fibrosis and progression to cirrhosis. Given the high prevalence of NAFLD, general measures of life-style changes, focusing on exercise, diet, and total alcohol abstinence, should be implemented before a liver biopsy is considered.

Aspartate Aminotransferases↗

Clinical features associated with improvement of fatty liver disease.

BACKGROUND: We presumed that identification of the factors associated with improvement of fatty livers disease (FLD) would support the therapeutic options for FLD. The goal of this study was to clarify what clinical characteristics are associated with biochemical and sonographic improvements in the non-alcoholic population with fatty livers. METHODS: A total of 615 non-alcoholic men had elevated alanine aminotransferase (ALT) (> or = 40 IU/L) levels and sonographic evidence of a fatty liver, and their clinical characteristics were assessed at the beginning of the study and after 1 year of follow up. The improvement was defined as combination of normal ALT level and negative sonography for hepatic fat after 1 year. Programmed intervention or medications were not applied in this study population. RESULTS: The overall rate of improvement of FLD after a 1-year follow up was 37/615 (6.0%). The improvement was strongly associated with decrement of changes in bodyweight, body mass index, waist circumference, gamma-glutamyltransferase, fasting blood sugar, total cholesterol, triglycerides, low-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol ratio and homeostasis model assessment. Multivariate analysis showed that decrement of changes in bodyweight (odds ratio (OR) = 1.56; 95% confidence interval (95%CI): 1.27-1.92) per 1 kg, body mass index (OR = 2.42; 95%CI: 1.58-3.71) per 1 SD (0.8 kg/m2), waist circumference (OR = 2.13; 95%CI: 1.02-4.54) per 1 cm, and low-density lipoprotein cholesterol (OR = 1.64; 95%CI: 1.05-2.56) per 1 SD (22 mg/dL) were all independent predictors for improvement of FLD. CONCLUSIONS: These results suggest that the reduction of bodyweight is a major key point for the improvement of FLD.

Adult↗

Fatty liver is an integral feature of familial combined hyperlipidaemia: relationship with fat distribution and plasma lipids.

Overproduction of VLDL (very-low-density lipoprotein) particles is an important cause of FCHL (familial combined hyperlipidaemia). It has been shown recently that VLDL production is driven by the amount of hepatic fat. The present study was conducted to determine the prevalence of fatty liver in relation to the different fat compartments and lipid parameters in FCHL. A total of 68 FCHL patients, 110 normolipidaemic relatives and 66 spouses underwent ultrasound of the abdominal region to estimate the amount of subcutaneous, visceral and hepatic fat. Skinfold callipers were used to measure subcutaneous fat of the biceps, triceps, subscapular and supra-iliacal regions. Fatty liver was observed in 18% of the spouses, 25% of the normolipidaemic relatives and 49% of the FCHL patients. After adjustment for age, gender and body mass index, the prevalence of fatty liver was significantly higher in FCHL patients compared with spouses [OR (odds ratio), 3.1; P=0.03], and also in the normolipidaemic relatives compared with spouses (OR, 4.0; P=0.02), whereas no differences were observed between FCHL patients and normolipidaemic relatives (OR, 0.8; P=0.58). In the normolipidaemic relatives and FCHL patients combined, both visceral fat mass and subcutaneous abdominal fat were independent predictors of fatty liver (P<0.001 for both fat compartments; FCHL status corrected). Of interest, fatty liver stages were correlated with both VLDL-apoB (apolipoprotein B) and VLDL-triacylglycerols (triglycerides) in a representative subset (n=69) of patients and relatives (r(2)=0.12, P=0.006; and r(2)=0.18, P=0.001 respectively). These results show that fatty liver is a central aspect of FCHL, i.e. patients and normolipidaemic relatives. Both visceral and subcutaneous adiposity contribute to its 3-4-fold higher risk in FCHL.

Adipose Tissue↗

Acute fatty liver of pregnancy after exposure to toluene. A case report.

We describe a patient in whom acute fatty liver of pregnancy developed after long-term toluene exposure. Acute fatty liver of pregnancy was documented by a liver biopsy specimen stained with oil red O and observed under electron microscopy. Although the mother did well, she gave birth to a stillborn whose autopsy showed visceral congestion and placental infarction. This case raises the hypothesis of a possible relationship between toluene exposure and acute fatty liver of pregnancy.

Acute Disease↗

Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults.

AIMS: To assess the prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with impaired glucose metabolism in Japanese subjects. METHODS: One thousand, nine hundred and fifty subjects enrolled in a general health examination programme from September 2002 to February 2003 were recruited. NAFLD was diagnosed if a person showed 'fatty liver' on ultrasonography, and his/her alcohol consumption, estimated by questionnaire, was < 40 gram/week. A general linear model was used for the comparison of estimated means of metabolic variables adjusted for age and body mass index (BMI) between subjects with NAFLD and those without fatty liver. Multivariate regression with fasting plasma glucose (FPG) as the dependent variable was performed in 1547 non-diabetic individuals after adjusting for age, gender, BMI and NAFLD. RESULTS: NAFLD was found in 566 of the 1950 health-check examinees (29%). Its prevalence increased with increasing FPG levels: 27% in the subgroup with normal fasting glucose, 43% in impaired fasting glucose and 62% in newly diagnosed diabetes. Adjusted means of FPG, HbA1c, triglyceride, total protein, albumin, AST and ALT were all significantly higher, while adjusted means of HDL cholesterol and AST/ALT ratio were significantly lower in subjects with NAFLD than those without fatty liver. Multivariate regression analysis showed that NAFLD was independently associated with increasing FPG in non-diabetic individuals. CONCLUSIONS: The prevalence of NAFLD was 29% in apparently healthy middle-aged Japanese adults and NAFLD was independently associated with impaired glucose metabolism.

Blood Glucose↗

[Acute fatty liver of pregnancy. Apropos of 4 cases: contribution of x-ray computed tomography].

Acute fatty liver of pregnancy is a disease of the third trimester, generally considered to be rare and to have a grave prognosis. Histologically the characteristic fine droplet steatosis usually produces distinct vacuolization. Successful treatment depends on accurate diagnosis and early delivery. Computed tomography is of value in the diagnosis of fatty liver through liver and spleen attenuation value measurements. We reviewed 4 cases of acute fatty liver of pregnancy. Computed tomography was performed in two cases and was very helpful in the diagnosis of this condition.

Acute Disease↗