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Focal nodular hyperplasia in normal and fatty liver: a qualitative and quantitative evaluation with contrast-enhanced ultrasound.

The aim of this study was to describe gray-scale appearance of liver parenchyma and focal nodular hyperplasia (FNH) by pulse inversion (PI) ultrasound (US) at baseline and after contrast agent administration in patients with normal and fatty liver. Sixteen consecutive patients (12 women, 4 men) with 29 previously diagnosed FNHs (15 of 29 located in normal liver and 14 of 29 in fatty liver) underwent PI US before and after SH U 508A (Levovist) injection. Signal intensity values were measured within the FNHs and the adjacent liver parenchyma in selected images. Baseline echogenicity of fatty liver was higher (15.19 +/- 2.90 dB +/- SD) than normal liver (10.91 +/- 3.15 dB +/- SD; p<0.001). After Levovist administration, normal livers (7 of 16) showed a statistically significant increase of echogenicity (16.59 +/- 3.81 dB +/- SD; p<0.001) in comparison with fatty livers (9 of 16; 15.75 +/- 3.12 dB +/- SD). The FNHs located in normal liver showed baseline echogenicity higher (12.29 +/- 3.22 dB +/- SD) than that of FNHs arising in fatty liver (7.06 +/- 2.43 dB +/- SD; p<0.001). After Levovist administration, FNHs located in normal liver showed a statistically significant increase of echogenicity (25.30 +/- 4.62 dB +/- SD) in comparison with FNHs located in fatty liver (13.58 +/- 3.54 dB +/- SD; p<0.001); the latter always showed mean values of echogenicity lower than surrounding liver parenchyma. In our series decreased contrast-enhancement pattern of both fatty liver and FNHs located in fatty liver was the most prominent finding when Levovist is administered. Contrast washout was a distinctive feature of FNH arising from the fatty liver.

Adult↗

[Clinical and experimental studies on changes in lysosomal enzyme activity in fatty livers (author's transl)].

In order to examine a role of lysosomes in the pathogenesis of fatty livers, analysis was made on possible etiologic factors, clinical signs and symptoms as well as laboratory data of routine liver function tests in 32 subjects with fatty livers. Of 18 cases, enzyme activities of serum acid phosphatase (Acp), beta-glucuronidase (betaG) and n-acetyl-beta-glucosaminidase (nbetaG) were measured and compared with those obtained in 20 normal subjects. Subjective symptoms were observed in 75% of the cases examined, liver swelling in 56%, positive GOT, GPT and BSP retention were in 59, 75 and 68%, respectively. The activity of serum lysosomal enzymes such as Acp, betaG and nbetaG were significantly increased and their incidence was 28, 89 and 78%, respectively. In animal experiments, activities of these enzymes in both serum and liver homogenate were examined in rats with choline-deficient, ethionine-treated, and alcoholic fatty livers. Results obtained were as follows: 1) Lysosomal enzyme activity in sera and livers of choline-deficient rats showed a significant decrease in lysosome-rich fraction and a significant increase in supernatant fraction and sera. 2) The enzyme activity in ethionine-treated rats decreased significantly in lysosome-rich fraction and tended to increase in supernatant fraction. The activity of betaG in sera increased markedly. 3) In rats given ethanol for 4 weeks, the enzyme activity of sera and liver homogenates significantly increased in lysosome-rich fraction. These results indicate that the analysis of serum lysosomal enzyme activity, in the light of clinical features and laboratory data of routine liver function tests, is useful for the diagnosis of the fatty liver. A discussion is given of a possible mode of variation of lysosomal enzymes in rats with fatty livers.

Acid Phosphatase↗

Decreased estradiol receptor concentrations in ethionine-induced fatty liver of rats.

Ethionine, a methionine analogue, induces fatty liver in rats. The mechanism by which ethionine induces fatty liver is thought to be due to the inhibition of synthesis of very-low-density lipoprotein. Since the synthesis of lipoprotein is correlated with liver estradiol receptor concentrations, we examined the effect of ethionine on estradiol receptor concentrations in rat liver. Estradiol receptor concentrations in both cytosolic and nuclear fractions were greatly decreased by a single injection of ethionine at a dose of 0.5 mg/g body wt. In particular, the decrease in nuclear receptor concentrations was observed a few hours after the injection and correlated with the decrease in triglyceride content in the very-low-density lipoprotein fraction. These results suggest that liver estradiol receptor is involved in the pathogenesis of ethionine-induced fatty liver of rats.

Animals↗

Are there any sex differences in fatty liver? A study of glucose metabolism and body fat distribution.

BACKGROUND AND AIMS: Fatty liver is a common condition found more often in males. Whether sex differences affect its development is presently unknown. The hypothesis that glucose metabolism alterations or central body fat distribution are gender-related in fatty liver was investigated. METHODS: Overall 199 consecutive subjects seen in the Division of Internal Medicine and Gastroenterology, Modena City Hospital, were enrolled. In the main arm of the present study, 44 men with sonographic fatty liver and 47 controls without, and 18 women with and 19 without fatty liver had their body mass index (an index of overall adiposity), hepatobiliary serum enzymes, serum cholesterol and triglycerides determined. All underwent oral glucose tolerance tests (estimated through the glucose area under the curve with the trapezoidal method). In the ancillary arm study, 17 other men with and 14 without, and 11 other women with and 29 without fatty liver had anthropometric measurements of body fat distribution (waist/hip, waist/height and skinfold thickness). RESULTS: Following statistical evaluation including univariate and multivariate analyses (main study), elevated body mass index was found to be an independent predictor of fatty liver in either sex. Glucose area under the curve and a central-type body fat distribution (ancillary study) predicted FL only in women. CONCLUSIONS: Fatty liver could be gender-related in the present series.

Body Mass Index↗

Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease.

Human nonalcoholic fatty liver disease (NAFLD) associated with obesity is characterized by depletion of hepatic n-3 long-chain polyunsaturated fatty acids (LCPUFA), with lower LCPUFA product/precursor ratios and higher 18:1n-9 trans levels in adipose tissue, both in patients with steatosis and in those with steatohepatitis. These changes point to modification of gene expression, with decreased fatty acid oxidation and triacylglycerol export and enhanced lipid synthesis, thereby leading to fat accumulation in the liver. Changes in oxidative stress-related parameters indicate a moderate enhancement in the pro-oxidant status of the liver in steatosis, which is further exacerbated in steatohepatitis. It is proposed that oxidative stress plays a dual role in NAFLD by contributing to steatosis due to higher peroxidation of LCPUFA, in addition to defective fatty acid desaturation and diet imbalance, and by promoting progression of steatosis to steatohepatitis, features that might involve changes in the activity of transcriptional mediators.

Animals↗

Prevalence of nonalcoholic fatty liver disease in coastal eastern India: a preliminary ultrasonographic survey.

Non-alcoholic fatty liver disease (NAFLD) is a common clinical condition which is fast assuming importance as a possible precursor of more serious liver disorders, including cirrhosis of the liver and hepatocellular carcinoma. There are no data in the published English literature on the prevalence of NAFLD in India. The present study was performed to assess a prevalence of NAFLD by ultrasonography in a general population in coastal eastern India. Asymptomatic, apparently healthy attendants accompanying the patients attending the Gastroenterology outpatient were subjected to abdominal ultrasonographic examination for the presence of fatty liver; individuals who gave a history of alcohol abuse were excluded from the study. The subjects of the study comprised 159 apparently healthy attendants, who underwent ultrasonography. Fatty liver was diagnosed by ultrasonography in 39 of these 159 persons (24.5%). Fatty liver was seen more commonly in males (26.9%) than in females (13.8%). Persons with ultrasonographic fatty liver had a higher body mass index (BMI) (mean 25.9 +/- 4.17 kg/m2) than persons without fatty liver (mean 22.1 +/- 3.27 kg/m2) (p<0.001). The estimated prevalence of NAFLD in an unselected apparently healthy and asymptomatic population as detected by ultrasonography in our study was found to be 24.5%. This is similar to the prevalence rate published from the west. However, contrary to figures from the west, males appeared to have a greater predilection for fatty liver than females in our study. NAFLD is perhaps as common in developing world as in the developed countries despite a lower prevalence of obesity. Indian males may have a greater genetic predisposition to developing NAFLD.

Adult↗

Clinical and histological features of non-alcoholic fatty liver disease in Hong Kong Chinese.

BACKGROUND: Non-alcoholic fatty liver disease is prevalent in affluent countries and is a cause of cirrhosis and possibly hepatocellular carcinoma. AIM: To examine the clinical and histological features of biopsy-proven non-alcoholic fatty liver disease and investigate the predictors of severe histological disease in Chinese patients. METHODS: Electronic records of all patients (n = 247) who underwent liver biopsy between 1996 and 2003 in our hospital were retrieved. Patients who had histological features of non-alcoholic fatty liver disease were identified. The demographic, clinical, laboratory and histological (Brunt's criteria) parameters of these patients were analysed. RESULTS: Forty-two patients had histology-proven non-alcoholic fatty liver disease. The median age was 47 years (range 23-69). All except one patient had features of metabolic syndrome. The median alanine aminotransferase was 93 (range 24-270) IU/L. Thirty-six (85.7%) patients had steatohepatitis and 11 (26.1%) also had fibrosis. Only one patient had stage 3 fibrosis. The presence of diabetes mellitus predicted higher grade steatohepatitis and fibrosis (P = 0.019) whereas alanine aminotransferase level had no correlation with histological severity of steatohepatitis. After a median follow-up of 42 months, no patient developed hepatic decompensation. CONCLUSIONS: Most Chinese patients with non-alcoholic fatty liver disease had features of the metabolic syndrome. Histological activity was generally mild. Diabetes mellitus was the most important predictor of severe histological disease.

Adult↗

Liver fatty acid binding protein expression in colorectal neoplasia.

Liver fatty acid binding protein is a member of the fatty acid binding group of proteins that are involved in the intracellular transport of bioactive fatty acids and participate in intracellular signalling pathways, cell growth and differentiation. In this study we have used proteomics and immunohistochemistry to determine the changes in liver fatty acid binding protein in colorectal neoplasia. Comparative proteome analysis of paired samples colorectal cancer and normal colon identified consistent loss of liver fatty acid binding protein (L-FABP) in colorectal cancer compared with normal colon. To identify the changes in liver fatty acid binding protein expression during colorectal cancer development and progression the cell-specific expression of L-FABP was determined by immunohistochemistry in a series of colorectal cancers and colorectal adenomas. Decreased L-FABP immunoreactivity was significantly associated with poorly differentiated cancers (P<0.001). In colorectal adenomas there was a significant trend towards decreased staining of L-FABP in the larger adenomas (P<0.001). There was consistent L-FABP immunostaining of normal surface colonocytes. This study demonstrates that loss of L-FABP occurs at the adenoma stage of colorectal tumour development and also indicates that L-FABP is a marker of colorectal cancer differentiation.

Adenoma↗

Studies on hepatic lipidosis and coinciding health and fertility problems of high-producing dairy cows using the "Utrecht fatty liver model of dairy cows". A review.

Fatty liver or hepatic lipidosis is a major metabolic disorder of high-producing dairy cows that occurs rather frequently in early lactation and is associated with decreased health, production and fertility. A background section of the review explores reasons why high-producing dairy cows are prone to develop fatty liver post partum. Hepatic lipidosis and coinciding health and fertility problems seriously endanger profitability and longevity of the dairy cow. Results from a great number of earlier epidemiological and clinical studies made it clear that a different approach was needed for elucidation of pathogenesis and etiology of this complex of health problems. There was a need for an adequate animal model in which hepatic lipidosis and production, health and fertility problems could be provoked under controlled conditions. It was hypothesized that overconditioning ante partum and feed restriction post partum might induce lipolysis in adipose tissue and triacylglycerol accumulation in the liver following calving. This consideration formed the basis for the experiments, which resulted in the "Utrecht fatty liver model of dairy cows". In this model, post partum triacylglycerol-lipidosis as well as the whole complex of health and fertility problems are induced under well-controlled conditions. The experimental protocol based on this hypothesis produced in all cases (10 feeding trials with over 150 dairy cattle) the intended result, i.e. all experimental cows developed post partum higher hepatic triacylglycerol concentrations than did control cows. The model was evaluated in biochemical, clinical pathology, immunological, clinical and fertility terms. It turned out that in this model, post partum triacylglycerol-lipidosis as well as the whole complex of health and fertility problems were induced under well-controlled conditions.

Animal Feed↗

Role of estrogen as a cause of fatty liver hemorrhagic syndrome.

Fatty liver-hemorrhagic syndrome (FLHS), a nutritional disorder previously reported only in laying chickens was induced in immature male and female chickens, 11 weeks of age, of broiler and egg-laying breeds. Force-feeding three times a day for 21 days, amounts of feed equal to 125% and 150% of ad libitum intake, produced a gradient response in hepatic steatosis (measured by percentage of fat in the liver, and the ratio of fat to the fat-free dry weight), but not FLHS. Intramuscular injection of beta-estradiol-17-dipropionate at 2 mg/kg body weight, three times weekly for 21 days, produced a gradient response in hemorrhagic score and an increase in ad libitum feed intake. There was no significant difference between sex or breed in the score values used to evaluate FLHS, but females of both breeds accumulated significantly more fat in the liver than males. Testosterone dipropionate at 25 mg/kg of body weight, injected three times per week in immature females force-fed at the 150% level, produced increases in food intake and liver fat as did estrogen, but no hepatic hemorrhaging. The data implicate estrogen as a factor in the production of FLHS along with the necessity for the chicken to be in a positive energy balance creating sufficient hepatic fat for FLHS to occur.

Animals↗

Hepatic gamma-glutamyltransferase activity in alcoholic fatty liver: comparison with other liver enzymes in man and rats.

Compared with controls, patients with alcoholic fatty liver showed a significant increase of gamma-glutamyltransferase activity both in the liver and serum, whereas alkaline phosphatase activity was raised only in the liver but not in the serum. The activities of other enzymes such as aspartate aminotransferase, alanine aminotransferase and glutamate dehydrogenase remained virtually unchanged in the liver of patients with alcoholic fatty liver but were strikingly enhanced in the serum. The hepatic and serum alterations of enzymic activities observed in patients with alcoholic fatty liver could be reproduced in the rat model of alcoholic fatty liver only for gamma-glutamyltransferase but not for the other enzymes tested, substantiating evidence that the animal model may serve as an appropriate tool for studying interactions between alcohol and gamma-glutamyltransferase. The present experiments also indicate that the primary cause for increased serum gamma-glutamyltransferase activities associated with prolonged alcohol consumption is hepatic enzyme induction rather than liver cell injury.

Adult↗

Clinical features and risk factors of patients with fatty liver in Guangzhou area.

AIM: There is still no accepted conclusion regarding the clinical features and related risk factors of patients with fatty liver. The large-scale clinical studies have not carried out yet in Guangzhou area. The aim of the present study was to investigate the clinical features and related risk factors of patients with fatty liver in Guangzhou area. METHODS: A total of 413 cases with fatty liver were enrolled in the study from January 1998 to May 2002. Retrospective case-control study was used to evaluate the clinical features and related risk factors of fatty liver with logistic regression. RESULTS: Obesity (OR: 21.204), alcohol abuse (OR: 18.601), type 2 diabetes mellitus (OR: 4.461), serum triglyceride (TG) (OR: 3.916), serum low-density lipoprotein cholesterol (LDL-C) (OR: 1.840) and fasting plasma glucose (FPG) (OR: 1.535) were positively correlated to the formation of the fatty liver. The levels of serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) increased mildly in the patients with fatty liver and were often less than 2-fold of the normal limit. The higher abnormalities of aspartate aminotransferase (AST) levels (42.9%) with AST/ALT more than 2(17.9%) were found in patients with alcoholic fatty liver (AFL) than those with nonalcoholic fatty liver (NAFL) (16.9% and 5.0% respectively). The elevation of serum TG, cholesterol (CHOL), LDL-C was more common in patients with NAFL than with AFL. CONCLUSION: Obesity, alcohol abuse, type 2 diabetes mellitus and hyperlipidemia may be independent risk factors of fatty liver. The mildly abnormal hepatic functions can be found in patients with fatty liver. More obvious damages of liver function with AST/ALT usually more than 2 were noted in patients with AFL.

Alanine Transaminase↗

Acute fatty liver of pregnancy: a clinicopathologic study of 35 cases.

Acute fatty liver of pregnancy is a disease of the third trimester which is generally considered to be rare and to have a grave prognosis. This study found an optimistic outlook for patients with acute fatty liver of pregnancy due to early termination of the pregnancy as well as the recognition of milder cases. In prospectively followed women, a maternal mortality of 8% and a fetal mortality of 14% were observed. The disorder also appears to be more common than previously suspected and should be considered in all women with liver dysfunction in late pregnancy, even if they are anicteric. Histologically, the characteristic fine droplet steatosis usually produces distinct vacuolization in sections stained with hematoxylin-eosin. However, early in the course of the illness, liver cells have a ballooned appearance and the presence of lipid is masked. When accompanied by a significant necroinflammatory reaction, this stage may be difficult to distinguish from acute viral hepatitis. Whenever acute fatty liver of pregnancy is suspected, a small piece of the biopsy should be reserved for special stains to confirm the presence of lipid in frozen sections. Significant loss of hepatic parenchyma is a regular accompaniment of acute fatty liver of pregnancy and is due to hepatocytolysis, acidophilic degeneration and liver cell atrophy. Extramedullary hematopoiesis and giant mitochondria are often present; the latter change is probably an adaptive or degenerative response to an altered metabolic environment. Despite the frequent presence of signs and symptoms of toxemia in patients with acute fatty liver of pregnancy, no histologic overlap was observed, suggesting that they represent distinct etiologic entities.

Adipose Tissue↗

[Epidemic survey on TCM syndrome typing and preliminary discussion on TCM etiology and pathogenesis of fatty liver].

OBJECTIVE: To investigate the common TCM syndrome types of fatty liver by way of epidemic questionnaire, their occurrence ratio, and the correlation between various syndrome types and objective indexes. METHODS: A total of national wide 503 subjects with fatty liver were enrolled, the TCM syndromes, body mass index (BMI), abdominal perimeter/hip circumference, liver function, blood lipids, B ultrasonic examination and CT in them were observed and recorded. RESULTS: In the 46 symptoms investigated in total, the first ten symptoms in order of appearing rate were lassitude, obese, oral dryness, vertigo, hypochondriac distending pain, soreness and pain in loin, spiritlessness, oral bitterness, aching and weakness in knee and abdominal distention. The mostly appeared tongue figures were pale and corpulent or pale dim tongue proper, white greasy or yellow greasy tongue coating, and the mostly appeared pulse figures were taut, taut-thin and taut slippery. Statistical cluster analysis showed that syndromes of fatty liver could be typed into 4 TCM types, the asthenia Pi-Shen with Gan-stagnation type, the asthenia Pi-Shen type, the asthenia Pi with phlegm-heat type and the unclassified type. Among them the asthenia Pi-Shen with Gan-stagnation type was the commonest one, which accounted to 62.32%. CONCLUSION: The mostly appeared syndrome type of fatty liver was asthenia Pi-Shen with Gan-stagnation type. The TCM pathogenesis of fatty liver was deficiency of origin, mainly deficiency of Shen, involving Pi, with excess superficiality, the turbid-phlegm and blood stasis.

Adolescent↗

Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey.

AIM: To determine the prevalence of nonalcoholic fatty liver in a specific population in Shanghai by an epidemiological survey, and to analyze risk factors of fatty liver. METHODS: Total 4009 administrative officers who denied regular alcohol drinking participated in the survey, and underwent physical examination and laboratory tests. The important parameters were body mass index (BMI), waist hip circumferences ratio (WHR) and levels of serum lipids. Diagnosis of fatty liver was based on established real-time ultrasonographic criteria, the presence of an ultrasonographic pattern consistent with "bright liver", with evident ultrasonographic contrast between hepatic and renal parenchyma, vessel blurring, and narrowing of the lumen of the hepatic veins. Analysis of data was performed through SPSS for Windows statistical package. RESULTS: The overall prevalence of fatty liver was 12.9 %, 15.8 % in males and 7.5 % in females, and the prevalence of fatty liver in males younger than 50 years old, was significantly higher (13.3 %) than that of in females (2.7 %). But the difference between the sexes became less significant in people older than 50 years (19.1 % vs 18.1 %). The prevalence of fatty liver was increased with age; this was markedly presented in females younger than 50 years. Multiple variant regression analysis demonstrated that the prevalence of fatty liver was positively correlated to several risk factors, including male, aging (>50yr), hyperlipidemia, impaired glucose tolerance/diabetes mellitus, hypertension and overweight/obesity. CONCLUSION: There is a high prevalence of nonalcoholic fatty liver among certain population in Shanghai, to which overweight and hyperlipidemia are closely relevant.

Adult↗

Cuproproteins of hepatocyte lysosomes in normal and fatty liver.

The pathophysiological significance of cuproproteins in hepatocyte lysosomes was studied in 7 patients with structurally normal livers and 13 patients with fatty livers by energy-dispersion X-ray microanalysis. In most patients, in both groups, copper and sulfur coexisted in hepatocyte lysosomes. The correlation between copper and sulfur indicated that copper transfer between the cytosol and lysosomes was mediated by a cuproprotein. The copper indices of the lysosomal proteins and transfer proteins were high in some fatty livers. These observations suggest that cuproproteins in hepatocytes are not necessarily pathological, but are present in greater amounts in some fatty livers, probably because of impaired bile drainage.

Adult↗