Fatty Liver Changes Research Articles

Acoustic Radiation Force Impulse Imaging of the Liver: Measurement of the Normal Mean Values of the Shearing Wave Velocity in a Healthy Liver

To find the normal mean values of the liver elasticity/stiffness by Acoustic Radiation Force Impulse (ARFI) Elastography in healthy subjects. This study was conducted on 137 healthy subjects without any known liver pathology or a history of jaundice by using the Siemens Acuson S2000TM Ultrasound machine with a convex probe . A routine ultrasound was also performed in each case, and the subjects with fatty liver changes or any other signs of a chronic liver pathology were excluded. In each subject, 10 measurements were taken and the median value of the 10 measurements was calculated, which was expressed in metres/sec (m/s). The inter quartile range method was used for the interpretation of the data. Only the measurements with an IQR of < 30% and a Success Rate (SR) of >60% were considered. The measurements were taken at 1-2 cm depth from the liver capsule through an intercostal approach, with the subject lying in the decubitus position. The mean ARFI values and the mean values according to the age and gender of the subjects were evaluated. Valid ARFI measurements were taken in 108/137 patients (78.83%). The mean value of the ARFI measurements in the normal individuals was 1.197±0.25 m/s. There were no significant differences between the mean ARFI values in men vs women (1.195±.25 vs. 1.199±0.26m/s, p = 0.939), and also among the different age groups (p>0.05). In our study, the mean liver elasticity value (shearing wave velocity) which was obtained by ARFI in the healthy subjects was 1.197±0.25 m/s.

Lessons Learned Regarding Symptoms of Tryptophan Deficiency and Excess from Animal Requirement Studies ,

Tryptophan is the precursor for several neurotransmitters and metabolic regulators, which, although quantitatively of little importance in determining the dietary requirement, have major importance for interpreting symptoms of dietary tryptophan deficiency and excess. The quantitative dietary tryptophan requirement appears to vary widely across species, so intakes relative to requirements are more appropriate expressions for comparison of adverse effects across species than daily intake or diet concentration. Symptoms of tryptophan deficiency may occur at intakes as little as 25% below the requirement. Symptoms include reduced feed intake and reduced growth rate but also impaired skeletal development and aberrant behavior. Older animals appear less susceptible than younger animals to tryptophan deficiency and females less than males. Symptoms of excess tryptophan intake include reduced food intake and growth rate. In growing animals, it appears that tryptophan intakes of >10 times the requirement are necessary before there are detrimental effects on growth performance. At still greater intakes, fatty liver and fibrotic changes in muscles, lung, and pancreas and the serotonin syndrome may develop. In pigs, tryptophan intake of 60 times the daily requirement did not cause mortality. The maximal tryptophan oxidation rate, measured in vivo using 13C universally labeled tryptophan, may be a possible marker of the intake above which increasing intake increases the risk of adverse effects. The advantage of the oxidation technique is that it does not necessarily rely on but still allows the identification and measurement of amino acid metabolites and is therefore simpler and more universally applicable.

Measurement of blood flow and xenon solubility coefficient in the human liver by xenon‐enhanced computed tomography

The goal of this work was to develop a method of calculating blood flow and xenon solubility coefficient (λ) in the hepatic tissue by xenon-enhanced computed tomography (Xe-CT) and to demonstrate λ can be used as a measure of fat content in the human liver. A new blood supply model is introduced which incorporates both arterial blood and portal venous blood which join and together flow into hepatic tissue. We applied Fick's law to the model. It was theoretically derived that the time course of xenon concentration in the inflow blood (the mixture of the arterial blood and the portal venous blood) can be approximated by a monoexponential function. This approximation made it possible to obtain the time-course change rate (K(I)) of xenon concentration in the inflow blood using the time course of xenon concentration in the hepatic tissue by applying the algorithm we had reported previously. K(I) was used to calculate blood flow and λ for each pixel in the CT image of the liver. Twenty-six patients (49.2 ± 18.3 years) with nonalcoholic steatohepatitis underwent Xe-CT abdominal studies and liver biopsies. Steatosis of the liver was evaluated using the biopsy specimen and its severity was divided into ten grades according to the fat deposition percentage [(severity 1) ≤ 10%, 10 % <(severity 2) ≤ 20%, [ellipsis (horizontal)], 90% < (severity 10) ≤ 100%]. For each patient, blood flow and λ maps of the liver were created, and the average λ value (λ) was compared with steatosis severity and with the CT value ratio of the liver to the spleen (liver∕spleen ratio). There were good correlations between λ and steatosis severity (r = 0.914, P < 0.0001), and between λ and liver∕spleen ratio (r = -0.881, P < 0.0001). Ostwald solubility for xenon in the hepatic tissue (tissue Xe solubility), which is calculated using λ and the hematocrit value of the patient, also showed a good correlation with steatosis severity (r = 0.910, P < 0.0001). λ ranged from 0.86 to 7.81, and tissue Xe solubility ranged from 0.12 to 1.16. This range of solubility is reasonable considering the reported Ostwald solubility coefficients for xenon in the normal liver and in the fat tissue are 0.10 and 1.3, respectively, at 37 °C. The average blood flow value ranged from 15.3 to 53.5 ml∕100 ml tissue∕min. A method of calculating blood flow and λ in the hepatic tissue was developed by means of Xe-CT. This method would be valid even if portosystemic shunts exist; it is shown that λ maps can be used to deduce fat content in the liver. As a noninvasive modality, Xe-CT would be applicable to the quantitative study of fatty change in the human liver.

해상가두리 양식장에서 배합사료 및 생사료 공급에 따른 조피볼락, Sebastes schlegeli의 병리조직학적 변화

A histo-pathogical examination was carried out to evaluate the effect of commercial extruded pellet (EP) and a raw fish moist pellet (MP) diet on the health of juvenile rockfish cultured in marine net-cage for 7 months. Fish were distributed randomly to each net cage as a group of 76,000 fish (initial mean body weight 5.9 g). After 2 months, the hypertrophy or swelling of liver parenchymal cells was identified in most individuals and lasted until 7 months. Livers in EP fed group frequently showed hypertrophic parenchyma and fatty change with occasional atrophic cells. However, after 4 months, lymphocytic infiltration in splenic parenchyma was seen in a number of individuals. In addition, the gastric glandular epithelium was atrophied and in the lumen of renal tubules protozoan parasites were frequently identified but there was no correlation with the type of feed. Moreover, juvenile rockfish on EP diet showed gross and microscopic hypertrophy of the liver which would be due to oversupply of feed. Severe hepatic cellular hypertrophy or swelling could lead to the damage of microcirculation. Especially fatty change and atrophic change of liver could be the result from the damage, which could be responsible for immunological problem. Lymphocytic infiltration of spleen on the MP diet suggests that juvenile rockfish could be frequently exposed to infectious antigens.

Perinatal Exposure to a High-Fat Diet Is Associated with Reduced Hepatic Sympathetic Innervation in One-Year Old Male Japanese Macaques

Our group recently demonstrated that maternal high-fat diet (HFD) consumption is associated with non-alcoholic fatty liver disease, increased apoptosis, and changes in gluconeogenic gene expression and chromatin structure in fetal nonhuman primate (NHP) liver. However, little is known about the long-term effects that a HFD has on hepatic nervous system development in offspring, a system that plays an important role in regulating hepatic metabolism. Utilizing immunohistochemistry and Real-Time PCR, we quantified sympathetic nerve fiber density, apoptosis, inflammation, and other autonomic components in the livers of fetal and one-year old Japanese macaques chronically exposed to a HFD. We found that HFD exposure in-utero and throughout the postnatal period (HFD/HFD), when compared to animals receiving a CTR diet for the same developmental period (CTR/CTR), is associated with a 1.7 fold decrease in periportal sympathetic innervation, a 5 fold decrease in parenchymal sympathetic innervation, and a 2.5 fold increase in hepatic apoptosis in the livers of one-year old male animals. Additionally, we observed an increase in hepatic inflammation and a decrease in a key component of the cholinergic anti-inflammatory pathway in one-year old HFD/HFD offspring. Taken together, these findings reinforce the impact that continuous exposure to a HFD has in the development of long-term hepatic pathologies in offspring and highlights a potential neuroanatomical basis for hepatic metabolic dysfunction.

Clinical and Needle Autopsy Correlation Evaluation in a Tertiary Care Teaching Hospital

With gradual fall in autopsy all over the world in recent years, the present study aimed to assess the accuracy of clinical diagnosis and efficacy of needle autopsy from the emergency department. Fifty deceased patients, who died in the emergency department during a period of 1 year, were subjected to needle autopsy of the major viscera, using spring-loaded automated biopsy gun, and the findings were correlated with clinical diagnosis. The deceased patients were in the age range of 12 to 80 years (mean [SD], 50.48 [18.41] years). The tissues yielded from various organs were as follows: lungs, 90%; liver, 82%; kidney, 48%; heart, 28%; spleen, 22%; and pancreas, 18%. Before death, 86 clinical diagnoses were recorded, of which 21 (24%) (eg, metabolic encephalopathy, cardiac arrhythmia, diabetic ketoacidosis) were impossible to verify on needle autopsy. A total of 48 new diagnoses, missed by physicians, were revealed by needle autopsy. The most frequently missed diagnoses were liver fatty change (19 patients) and pneumonitis (11 patients). Other frequently missed diagnoses were chronic hepatitis (3 patients) and cancer (2 patients: 1 lung squamous cell carcinoma and 1 lung adenocarcinoma). Major diagnostic errors (Goldman classes I and II) were noted in 16 (32%) of 50 cases. Needle autopsy can be a better alternative in the absence of conventional autopsy.

Predictive Factors of Sustained Virological Response for Recurrent Hepatitis C Virus After Liver Transplantation: The Hungarian Experience

Recurrence of hepatitis C virus (HCV) after liver transplantation (OLT) occurs consistently. Early initiation of combined antiviral treatment (AVT) has become a standard treatment seeking to achieve sustained virological response (SVR). We evaluated the files of 108 HCV-positive patients between 2003 and 2010. Seventy-two (72) experienced recurrent HCV within 12 months, 31 of whom completed the AVT (43%) but 9 (29%) exhibited SVR. Factors with impacting SVR were male recipient, no fatty changes in the donor liver, short warm ischemia time, cyclosporine-based immunosuppression, neither infective, septic or bleeding complication nor acute rejection episode and a rapid viral response to AVT. De novo diabetes, and unsuccessful AVT prior to OLT were strongly associated with a a failed SVR. The 1- and 3-year cumulative patient survival rates trended to be better in cases of SVR compared with nonresponders (100% and 100% versus 94% and 89%; P = .07).

Niacin Ameliorates Lipid Disturbances due to Glucocorticoid Administration in Rats.

This study was conducted to evaluate the effects of niacin on glucocorticoid-induced dyslipidemia and fatty liver in rats. TWENTY FOUR ADULT MALE RATS WERE DIVIDED RANDOMLY INTO FOUR EQUAL GROUPS: 1- normal saline (control), 2- dexamathasone 0.125 mg/kg/day, i.m., 3- dexamathasone + niacin 200 mg/kg/day, oral gavages, 4- niacin. After 2 weeks, serum total cholesterol, triglycerides, HDL-c, LDL-c and VLDL-c concentrations were assayed and liver sections examined for fatty liver changes. Data were analyzed by ANOVA method and P< 0.05 was considered significant. Dexamethasone increased all lipid parameters as compared to control (P< 0.05). Lipid parameters in group 3, were lower than group 2 (P< 0.05) except for HDL-c which remained statistically the same. Moderate fatty liver changes were observed in one third of rats in dexamethasone group. Rats in groups 1, 3 and 4 had no sign of fatty changes. Niacin positively affects glucocorticoid-induced dyslipidemia and fatty liver changes in rats.

Pathophysiological analysis of nonalcoholic fatty liver disease by evaluation of fatty liver changes and blood flow using xenon computed tomography: can early-stage nonalcoholic steatohepatitis be distinguished from simple steatosis?

Effective noninvasive tests that can distinguish early-stage nonalcoholic steatohepatitis (NASH) from simple steatosis (SS) have long been sought. Our aim was to determine the possibility of noninvasively distinguishing early-stage NASH from SS. We used Fick's principle and the Kety-Schmidt equation to determine the hepatic tissue blood flow (TBF) in 65 NASH patients who underwent xenon computed tomography (Xe-CT). We calculated the lambda value (LV), i.e., Xe gas solubility coefficient, in liver and blood. We assessed the histological severity of fatty changes and fibrosis on the basis of Brunt's classification. Liver biopsy revealed SS in 9 patients and NASH in 56 patients. NASH stages 1 and 2 were classified as early-stage NASH (Ea-NASH; 38 patients) and stages 3 and 4 as advanced-stage NASH (Ad-NASH; 18 patients). We evaluated the differences in LV and TBF among the 3 groups. LV was significantly lower in the Ad-NASH group than in the SS and Ea-NASH groups. Portal venous TBF (PVTBF) was significantly lower in the Ea-NASH group than in the SS group, and PVTBF was lower in the Ad-NASH group than in the Ea-NASH group. Total hepatic TBF (THTBF) was significantly different between the SS and Ea-NASH groups and between the SS and Ad-NASH groups. In conclusion, measurements of TBF and LV are useful for evaluating the pathophysiological progression of NASH. In addition, these measurements can facilitate the differential diagnosis of SS and Ea-NASH, which may not be distinguishable by other means.

The proton pump inhibition removes alcoholic fatty liver disease via inactivation of TLR signaling pathway

Pathogenesis of alcoholic fatty liver disease has never been established. It has been that TLR‐signaling pathway plays an important role in the development. What primes TLR‐signaling pathway and any prevention remains unclear. The proton pump exists in endosome in macrophage. Endosome includes TLR4, TLR7 and TLR9, which may contribute to innate immune response in macrophage. We hypothesized that inhibition of proton pump reduces alcoholic fatty liver disease. To clarify the hypothesis, we evaluated fatty liver injury in alcohol‐fed rats after treatment with a proton pump inhibitor. Male Wistar rats were fed with Lieber‐DeCarli alcohol liquid diet for 4 weeks. Lansoprazol, a proton pump inhibitor, was treated to alcohol liquid diet‐fed rats. Immunohistochemical staining for TLR7 and TLR9 was performed in formalin‐fixed, paraffin‐embedded liver sections. ER stress markers were analyzed by quantitative real‐time PCR. Alcohol feeding caused expression of TLR7 and TLR9 and accumulation of ER stress. Inhibition of proton pump results in reduction of fatty liver change, especially lipid droplets in hepatocytes and no staining for TLR7 and TLR9. However, accumulation of ER stress was not changed by inhibition of proton pump. Therefore, chronic alcohol consumption causes developing fatty liver disease via TLR7 and TLR9, which expression can be reduced by inhibition of proton pump.

Large Scale Study of H1N1 Influenza Cases: A Novel Approach Using Post-Mortem Needle Biopsy

Considering few H1N1 pathology reports based on autopsies & biopsy studies only in seasonal influenza; our series of 70 postmortem needle biopsies in H1N1 Influenza is worth documenting. Decedents with severe respiratory illness & strong clinical suspicion of H1N1 influenza in 2009 pandemic were studied. Nasopharyngeal swabs for RT-PCR & post mortem biopsies were taken. 51.4% were H1N1 positive & 48.6% were negative on RT-PCR. Most of H1N1+ve cases showed interstitial pneumonia & intra-alveolar hemorrhages & DAD in lung & fatty change in liver. Similar histopathology of majority of H1N1 RT-PCR negative & positive cases prompts need for confirmation of negative cases by ancillary methods. Rapid & safe diagnosis of H1N1 Influenza can be obtained by biopsy if supplemented by IHC to get accurate estimate of disease prevalence & mortality. Sufficient biopsy sampling can provide insight into H1N1influenza pathology & eliminate need for autopsies considering high infectivity of disease.

Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism

Although peroxisome proliferator receptor (PPAR)-α and PPAR-γ agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-δ has not been fully investigated. In this study, we examined the effects of the PPAR-δ agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-δ agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-γ coactivator (PGC)-1α gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-α and MCP-1 was also examined in supernatant of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-α, MCP-1, and PGC-1α were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-δ agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1α gene expression, and improvement of insulin signaling.

Metabolic profiling of an alcoholic fatty liver in zebrafish (Danio rerio)

Zebrafish (Danio rerio) is becoming a popular developmental biology model to study diseases and for drug discovery. In this study, we performed proton nuclear magnetic resonance spectroscopy ((1)H-NMR)- and gas chromatography-mass spectrometry (GC/MS)-based metabolic profiling of an alcoholic fatty liver using a zebrafish disease model. We examined metabolic differences between the control and alcoholic fatty liver groups in zebrafish to determine how metabolism in an alcoholic fatty liver is regulated. Multivariate statistical analysis showed a significant difference between the control and alcoholic fatty liver groups. The alcoholic fatty liver group showed increased excretion of isoleucine, acetate, succinate, choline, creatine, acetoacetate, 3-hydroxybutyrate (3HB), ethyl glucuronide (EtG), lactate/pyruvate ratio, fatty acids, and cholesterol, and decreased excretion of citrate, aspartate, tyrosine, glycine, glucose, alanine, betaine, and maltose. Metabolites identified in the fatty liver groups were associated with long-term alcohol consumption, which causes both oxidation-reduction (redox) changes and oxidative stress. This study suggests that global metabolite profiling in a zebrafish model can provide insights into the metabolic changes in an alcoholic fatty liver.

Body composition, C-reactive protein, carotid artery remodeling and subclinical atherosclerosis in a general Taiwanese population

Obesity, an escalating problem worldwide, increases the risk of serious disease, particularly atherosclerosis. A community-based cross-sectional study was designed to screen for undetected atherosclerosis. High-sensitivity C-reactive protein (hs-CRP), the presence of the metabolic syndrome (MetS), and ultrasound studies to detect fatty liver and measure carotid intimal-medial thickness were performed. A total of 1,005 subjects (595 men and 410 women; mean age of 52.4 ± 11.1 years) were included in the final study cohort. 237 subjects (23.7%) fulfilled National Cholesterol Education Program Adult Treatment Panel ATP-III criteria for MetS. Significant differences between female and male subjects were noted in body mass index (BMI), % body fat mass (Fat%), waist-to-hip ratio, waist circumference, fasting glucose levels, triglyceride levels, fatty liver, and carotid artery changes (P < 0.05). When female subjects were classified by hs-CRP levels, significant differences were reported among the three groups in age, BMI, Fat%, waist-to-hip ratio, waist circumference, blood pressure, fasting glucose, HDL, triglycerides, fatty liver grade and common carotid artery changes (P < 0.05). In this study, high hs-CRP was associated with increased cholesterol and cardiovascular changes supporting the idea that it may be a useful biomarker for detecting early asymptomatic vascular and coronary heart disease resulting from obesity.

Obesity and Air Pollution: Global Risk Factors for Pediatric Non-alcoholic Fatty Liver Disease

: Non-alcoholic fatty liver disease (NAFLD) is becoming as an important health problem in the pediatric age group. In addition to the well-documented role of obesity on the fatty changes in liver, there is a growing body of evidence about the role of environmental factors, such as smoking and air pollution, in NAFLD. Given that excess body fat and exposure to air pollutants is accompanied by systemic low-grade inflammation, oxidative stress, as well as alterations in insulin/insulin-like growth factor and insulin resistance, all of which are etiological factors related to NAFLD, an escalating trend in the incidence of pediatric NAFLD can be expected in the near future. This review focuses on the current knowledge regarding the epidemiology, diagnosis and pathogenesis of pediatric NAFLD. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for broadening efforts in prevention and control of the main risk factors. The two main universal risk factors for NAFLD, obesity and air pollution, have broad adverse health effects, and reducing their prevalence will help abate the serious health problems associated with pediatric NAFLD. Implication for health policy/practice/research/medical education:Nonalcoholic fatty liver disease (NAFLD) is becoming as an important health problem for children and adolescents.In addition to excess weight, the role of environmental factors, as smoking and air pollution should be considered in this regard. This study is recommended to specialists in internal medicine, pediatrics,environmental health , general practitioners, health policy makers, and health professionals. Please cite this paper as:Kelishadi R, Poursafa P. Obesity and Air Pollution: Global Risk Factors for Pediatric Non-alcoholic Fatty Liver Disease. Hepat Mon.2011;11(10):794-802. DOI: 10.5812/kowsar.1735143X.746 © 2011 Kowsar M.P.Co. All rights reserved.

Obesity and Air Pollution: Global Risk Factors for Pediatric Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is becoming as an important health problem in the pediatric age group. In addition to the well-documented role of obesity on the fatty changes in liver, there is a growing body of evidence about the role of environmental factors, such as smoking and air pollution, in NAFLD. Given that excess body fat and exposure to air pollutants is accompanied by systemic low-grade inflammation, oxidative stress, as well as alterations in insulin/insulin-like growth factor and insulin resistance, all of which are etiological factors related to NAFLD, an escalating trend in the incidence of pediatric NAFLD can be expected in the near future. This review focuses on the current knowledge regarding the epidemiology, diagnosis and pathogenesis of pediatric NAFLD. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for broadening efforts in prevention and control of the main risk factors. The two main universal risk factors for N LD, obesity and air pollution, have broad adverse health effects, and reducing their prevalence will help abate the serious health problems associated with pediatric NAFLD.

The In Utero Programming Effect of Increased Maternal Androgens and a Direct Fetal Intervention on Liver and Metabolic Function in Adult Sheep

Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS). We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin–like growth factor (IGF) and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5) or testosterone propionate (TP; n = 9) twice weekly (100 mg; i.m) from d62–102 (gestation 147 days). In a novel treatment paradigm, a second cohort received a direct C (n = 4) or TP (20 mg; n = 7) fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05) and the histological presence of fatty liver (P<0.05) independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05), glucocorticoid receptor (GR; P<0.05), UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05) and IGF1 (P<0.01) expression were upregulated. The direct fetal intervention (C and TP) led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated in the fetal controls (P<0.05) and this was opposed by fetal TP (P<0.05). Hepatic estrogen receptor (ERα; P<0.05) and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05) were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.

Characterization of hepatocellular adenoma based on the phenotypic classification: The Kanazawa experience

Hepatocellular adenoma (HCA) represents a heterogeneous entity, and recently four major subgroups were identified based on genotype and phenotype classification from Europe. HCA is rare in Asian countries including Japan and there has been no study regarding the subgroups of HCA in Japan. We took advantage of the reported genotype/phenotype classification to analyze 14 HCA (seven women) in Japan. We identified one hepatocyte nuclear factor (HNF)1α-inactivated HCA (one woman), two β-catenin-activated HCA (one woman), seven inflammatory HCA (IHCA, two women); four additional cases (three women) had no known phenotypic marker (unclassified HCA). The use of oral contraceptives was found only in two unclassified HCA (29%) cases. Fatty change of the background liver was seen in one β-catenin-activated HCA cases, four IHCA (57%) and two unclassified HCA (50%). Hepatic fibrosis was seen in five IHCA (71%) and two unclassified HCA (50%) cases. Four IHCA patients (one woman) were alcohol drinkers and one had alcoholic steatofibrosis and three had alcoholic cirrhosis. Eight HCA (57%) were multiple; one HNF1α-inactivated HCA (100%), four IHCA (57%) and three unclassified HCA (75%). The tumor was significantly larger in β-catenin-activated HCA than in other subgroups. The association of hepatocellular carcinoma was seen only in one case of unclassified HCA. This study suggests that IHCA arising in men with alcoholic liver disease may be a major subtype of HCA in Japan.

Assessment of dermal exposure and histopathologic changes of different sized nano-silver in healthy adult rabbits

The purpose of this study is to evaluate the dermal toxicity (Irritation/Corrosion) of three sizes of nanosilver particles (10, 20 and 30 nm) during 3 min, 1 and 4 hours according to the OECD/OCDE guideline Histopathological effects in secondary organs from liver, kidney, heart, spleen and brain 14 day post dermal administration are also reported. 10 and 20 nm Ag nanoparticles treated group showed well defined dermal erythema and oedema. Histopathological findings of 10 and 20 nm (4 hours exposure) on 14-day post dermal administration showed hyperkeratosis, acanthosis, hair-filled follicles and papillomatosis in an irregular epidermis, fibrosis, hyperemia, erythema, intracellular oedema and hyalinisation of collagen in dermis of skin. Liver revealed midzonal and periacinar necrosis, portal mononuclear infiltration, liver fatty change, liver congestion and hyperemic central vein. Splenic red pulp congestion and white pulp hyperreactivity, splenic trabeculae and sinusoidal congestion and hyaline change were found in spleen. Fatty degeneration in some cardiovascular cells and subendocardial hemorrhage without inflammation was perceived. Picnotic appearance of pyramidal neurons in the brain cortex, gliosis and mild perineuronal oedema ischemic cell change and hyperemic meninges was observed in brain. Our research concluded that dermal exposure to lesser sizes of silver nanoparticles is more disastrous than greater ones.

Elevated serum liver enzymes and fatty liver changes associated with long driving among taxi drivers

Previous studies suggested increased morbidities and mortalities of liver diseases in drivers. To examine whether driving (monthly driving distance; tenure) is associated with elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), or chronic fatty liver (FL) changes, we performed a cross-sectional, secondary analysis of the Taxi Drivers' Health Study (n = 1,355), adjusting for clinical, demographic, and lifestyle factors. Prevalence of elevated ALT, elevated AST, and fatty liver changes were 22.0%, 5.1%, and 9.3%, respectively. Driving distance had a positive association with elevated ALT with a prevalence ratio of 1.35 (95% CI: 0.98, 1.89) comparing the highest versus lowest driving quartile. This association differed by alcohol use, with a corresponding prevalence ratio of 2.08 (95% CI: 1.30, 3.33) among "past/current" drinkers but no association among "never" drinkers. Similar patterns were found for AST, but estimates were less stable. We found a curvilinear response pattern for fatty liver changes; prevalence first increased with years as a taxi driver and then receded in the highest ranges of driving tenure, regardless of the alcohol history. Our results provide evidence that long driving is associated with both short-term and chronic liver insults, although alcohol use appears to modify this putative effect.