Evaluation of Hepatic Fibrosis and Hepatic Steatosis by Pulse Elastography (FIBROSCAN/CAP) in Asymptomatic Patients about 170 Cases at the Donka CHU National Hospital in Conakry

Introduction: Fibroscan is a recent, non-invasive and non-irradiating diagnostic method. It is based on the principle of ultrasound, which enables liver tissue elasticity to be quantified using a probe, and fibrosis to be assessed. Fibroscan measures both elasticity correlated with hepatic fibrosis and CAP correlated with steatosis. The aim of this study was to evaluate hepatic fibrosis and steatosis using pulse elastometry (Fibroscan/CAP). Methods: This was a descriptive and analytical cross-sectional study in which 170 patients were included. It was conducted from October 1 2021 to December 31 2023, i.e. 27 months, in an outpatient clinic in the hepato-gastroenterology department of the Donka national hospital of the CHU Conakry. Results: Of the 170 patients identified, 87 were male (51%) and 83 female (49%), giving a M/F sex ratio of 1.04. The average age of our patients was 40. The 30 - 50 age group was the most affected, with a frequency of 58.23% (n = 99), followed by the 50 age group with a frequency of 29.41% (n = 50). Hepatomegaly, steatotic liver on ultrasonography, transaminase elevation and obesity were the main indications, respectively: (21.76%), (17.65%), (14.71%), and (13.53%). The examinations were requested by hepatogastroenterologists (47.06%), diabetologists (35.88%) and general practitioners (29%). Of the 170 patients, 100 patients (58.82%) had no significant fibrosis F0F1, 39 (22.94%) had moderate fibrosis F2, 20 patients (11.76%) had severe fibrosis F3 and 11 patients (6.47%) had fibrosis F4. Hepatic steatosis: 62 patients (36.47%) had no S0 steatosis;29.41% had S1 steatosis, 20% had S2 steatosis and 24 patients (14.11%) had S3 steatosis. Abdominal ultrasound revealed a normal liver in 67.05% of patients, hepatic steatosis in 29.41% and non-decompensated cirrhosis in 6 cases. Thus, 108 patients had the parameters required to calculate the Fatty Liver Index (FLI), steatosis was present in 20% of our patients, while 29.41% had an undetermined status and 24 14.11% had a normal FLI. Conclusion: Identifying subjects at risk of metabolic steatopathy, diagnosing and managing these patients is a public health issue and one of the future challenges of hepato-gastroenterology. Fibroscan is an increasingly popular screening tool for hepatic fibrosis and steatosis. The fight against obesity must be a priority.

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease

AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis(CF) patients with hepatic steatosis as compared to normal CF controls.METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging(ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls.RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients(14.9%) were found to have hepatic steatosis on imaging. Being overweight(BMI > 25)(P = 0.019) and having a higher pp FEV1(75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level(27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes.CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher pp FEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.

Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

Hepatic steatosis is associated with dysregulated cholesterol metabolism and altered protein acetylation dynamics in chickens

Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.

Non-invasively differentiate non-alcoholic steatohepatitis by visualizing hepatic integrinαvβ3 expression with a targeted molecular imaging modality

BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrinαvβ3-targeted molecular imaging modality to differentiate NASH.METHODS Integrinαvβ3 expression was assessed in Human LO2 hepatocytes Scultured with palmitic and oleic acids(FFA).Hepatic integrinαvβ3 expression was analyzed in rabbits fed a high-fat diet(HFD)and in rats fed a high-fat,high-carbohydrate diet(HFCD).After synthesis,cyclic arginine-glycine-aspartic acid peptide(cRGD)was labeled with gadolinium(Gd)and used as a contrast agent in magnetic resonance imaging(MRI)performed on mice fed with HFCD.RESULTS Integrinαvβ3 was markedly expressed on FFA-cultured hepatocytes,unlike the control hepatocytes.Hepatic integrinαvβ3 expression significantly increased in both HFD-fed rabbits and HFCD-fed rats as simple fatty liver(FL)progressed to steatohepatitis.The distribution of integrinαvβ3 in the liver of NASH cases largely overlapped with albumin-positive staining areas.In comparison to mice with simple FL,the relative liver MRI-T1 signal value at 60 minutes post-injection of Gd-labeled cRGD was significantly increased in mice with steatohepatitis(P<0.05),showing a positive correlation with the NAFLD activity score(r=0.945;P<0.01).Hepatic integrinαvβ3 expression was significantly upregulated during NASH development,with hepatocytes being the primary cells expressing integrinαvβ3.CONCLUSION After using Gd-labeled cRGD as a tracer,NASH was successfully distinguished by visualizing hepatic integrinαvβ3 expression with MRI.

Hepatic steatosis,low-grade chronic inflammation and hormone/growth factor/adipokine imbalance

Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.

Accuracy of multi-echo Dixon sequence in quantification of hepatic steatosis in Chinese children and adolescents

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) is currently the outstanding cause of chronic liver disease in children and adolescents, especially in overweight and obese groups. Liver biopsy is the reference standard to diagnose NAFLD but invasive, thus it is not the best choice in clinical diagnosis and follow-up.Magnetic resonance(MR) is widely used in clinical trials to noninvasively quantify liver fat content in adults and children in foreign countries. While currently, it is rarely used in Chinese children and adolescents. We postulated that quantifying hepatic steatosis by MR could be extended to children and adolescents in China.AIM To investigate the accuracy of MR imaging(MRI) in quantifying liver fat with MR spectroscopy(MRS) as a reference. A secondary goal was to assess the prevalence of NAFLD in overweight and obese Chinese children and adolescents.METHODSThere were 86 children and adolescents enrolled in this study, including 65 overweight and obese children and 21 healthy children. The participants underwent MRI and MRS. MRI and MRS were performed using multi-echo Dixon and HISTO sequences, respectively, to calculate hepatic proton density fat fraction(PDFF). Hepatic steatosis was diagnosed using MRS-PDFF > 5% as the threshold. Spearman's analysis was used to evaluate the correlation between MRI and MRS. The agreement between these two methods was assessed by BlandAltman analysis.RESULTS The MRI-PDFF in the MRS region of interest and the entire liver was 9.9% ±10.3% with a range of 0.3%-39.9%, and 10.6% ± 9.4% with a range of 1.9%-38.9%,respectively. The MRS-PDFF was 9.1% ± 10.0%, with a range of 0.5%-37.8%. The incidence of hepatic steatosis detected by MRS-PDFF was 46.5%(40/86) of all participants, all of whom belonged to the overweight and obese group.Spearman's analysis indicated an excellent correlation between multi-echo Dixon and MRS(r > 0.9, P < 0.01). Bland-Altman analysis also demonstrated a good agreement between these two methods.CONCLUSION Multi-echo Dixon shows an excellent correlation and agreement with MRS in quantifying liver fat content and could be a potential tool to detect hepatic steatosis in Chinese children and adolescents.

Modulation of hepatic steatosis by dietary fatty acids

Non-alcoholic fatty liver disease (NAFLD) describes a range of conditions caused by fat deposition within liver cells. Liver fat content reflects the equilibrium between several metabolic pathways involved in triglyceride synthesis and disposal, such as lipolysis in adipose tissue and de novo lipogenesis, triglyceride esterification, fatty acid oxidation and very-low-density lipoprotein synthesis/secretion in hepatic tissue. In particular, it has been demonstrated that hepatic de novo lipogenesis plays a significant role in NAFLD pathogenesis. It is widely known that the fatty acid composition of the diet influences hepatic lipogenesis along with other metabolic pathways. Therefore, dietary fat may not only be involved in the pathogenesis of hepatic steatosis, but may also prevent and/or reverse hepatic fat accumulation. In this review, major data from the literature about the role of some dietary fats as a potential cause of hepatic fat accumulation or as a potential treatment for NAFLD are described. Moreover, biochemical mechanisms responsible for an increase or decrease in hepatic lipid content are critically analyzed. It is noteworthy that both quantitative and qualitative aspects of dietary fat influence triglyceride deposition in the liver. A high-fat diet or the dietary administration of conjugated linoleic acids induced hepatic steatosis. In contrast, supplementation of the diet with krill oil or pine nut oil helped in the prevention and/or in the treatment of steatotic liver. Quite interesting is the &#x0201c;case&#x0201d; of olive oil, since several studies have often provided different and/or conflicting results in animal models.

A study of the ameliorating effects of carnitine on hepatic steatosis induced by total parenteral nutrition in rats

AIM To investigate the effects of carnitine on ameliorating hepatic steatosis induced by total parenteral nutrition (TPN) in animal model. METHODS Eighteen normal Wistar rats and 19 cirrhotic Wistar rats induced by carbon tetrachloride were randomly divided into three groups, i.e., free access to food and drink (group A), TPN (group B) and TPN+carnitine (group C) for one week, respectively. Hepatic function, histology and its fat content were determined on the 7th day. RESULTS Hepatic triglyceride (TG) and cholesterol (CHO) contents were significantly higher in groups B and C than in group A, and significantly lower in group C than in group B in both normal and cirrhotic rats (all P <0 05). Histopathological examinations revealed that hepatic steatosis was more severe in group B than in group C in both normal and cirrhotic rats. CONCLUSION Carnitine can ameliorate hepatic steatosis associated with TPN in both non cirrhotic and cirrhotic rats.

Significance of serum leptin and adiponectin levels in Egyptian patients with chronic hepatitis C virus associated hepatic steatosis and fibrosis

AIM:To study serum levels of leptin and adiponectin in patients with chronic hepatitis C virus infection genotype-4(HCV-4) related steatosis and fibrosis.METHODS:We prospectively studied 45 untreated men with chronic HCV-4,with proven steatosis(group Ⅰ,30 patients),and fibrosis(group Ⅱ,15 patients),on liver biopsy.In addition,15 healthy men(group Ⅲ),matched for age,and body mass index were included.However,we excluded another five patients with steatohepatitis,and six patients with cirrhosis.We measured total serum leptin and adiponectin levels,as potential predictors for liver steatosis and fibrosis.Also,a correlation between these adipokines and various clinical and laboratory data were evaluated.All subjects were selected from Tropical and Internal medicine departments,Menoufiya University Hospital,Menoufiya,Egypt,during the period from February 2010 to August 2011.RESULTS:In group Ⅰ,severity of hepatic steatosis was mild,moderate,and severe,in 19 patients(63.5%),8 patients(26.5%),and 3 patients(10%),respectively.In contrast,in group Ⅱ,hepatic fibrosis was found to be in stage 1,2,and 3,in 6 patients(40%),in 6 patients(40%),and in 3 patients(20%),respectively.On comparing group Ⅰ with group Ⅱ,there was a significant decrease in serum adiponectin levels(131.4 ± 7.91 pg/mL vs 436 ± 9.75 pg/mL,P < 0.001),while there was no significant difference between both groups regarding serum leptin levels(34.69 ± 7.69 ng/mL vs 35.17 ± 1.06 ng/mL,P > 0.05).However,in the same group,when compared with group Ⅲ,there was a significant increase in serum leptin levels(34.69 ± 7.69 ng/mL vs 10.69 ± 0.84 ng/mL,P < 0.001),while there was a significant decrease in serum adiponectin levels(131.4 ± 7.91 pg/mL vs 342.4 ± 44.48 pg/mL,P < 0.001).In contrast,in group Ⅱ,when compared with group Ⅲ,there was a significant increase in serum leptin and adiponectin levels(35.17 ± 1.06 ng/mL vs 10.69 ± 0.84 ng/mL,P < 0.001,and 436 ± 9.75 pg /mL vs 342.4 ± 44.48 pg/mL,P < 0.05,respectively),while there was no significant difference between both groups regarding serum creatinine(0.83 ± 0.34 vs 0.89 ± 0.24,P > 0.05).On the other hand,serum leptin was not correlated with serum adiponectin in group Ⅰ and in group Ⅱ(r = 0.09,P > 0.05,and r =-0.1,P > 0.05,respectively).However,serum adiponectin was significantly negatively correlated with serum aspartate transaminase in group Ⅰ,but no correlation detected in group Ⅱ(r =-0.39,P > 0.05,and r =-0.03,P > 0.05).CONCLUSION:In male patients with chronic HCV-4,serum adiponectin levels are elevated in hepatic fibrosis,but decreased in steatosis.Therefore,in contrast to leptin,adiponectin may be used as a non-invasive marker.

Ezetimibe improves hepatic steatosis in relation to autophagy in obese and diabetic rats

AIM: To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes. METHODS: Male age-matched lean control LETO and obese and diabetic OLETF rats were administered either PBS or ezetimibe(10 mg/kg per day) via stomach gavage for 20 wk. Changes in weight gain and energy intake were regularly monitored. Blood and liver tissue were harvested after overnight fasting at the end of study. Histological assessment was performed in liver tissue. The concentrations of glucose, insulin, triglycerides(TG), free fatty acids(FFA), and total cholesterol(TC) in blood and TG, FFA, and TG in livertissue were measured. m RNA and protein abundance involved in autophagy was analyzed in the liver. To investigate the effect of ezetimibe on autophagy and reduction in hepatic fat accumulation, human Huh7 hepatocytes were incubated with ezetimibe(10 μmol/L) together with or without palmitic acid(PA, 0.5 mmol/L, 24 h). Transmission electron microscopy(TEM) was employed to demonstrate effect of ezetimibe on autophagy formation. Autophagic flux was measured with bafilomycin A1, an inhibitor of autophagy and following immunoblotting for autophagy-related protein expression.RESULTS: In the OLETF rats that received ezetimibe(10 mg/kg per day), liver weight were significantly decreased by 20% compared to OLETF control rats without changes in food intake and body weight(P < 0.05). Lipid parameters including TG, FFA, and TC in liver tissue of ezetimibe-administrated OLETF rats were dramatically decreased at least by 30% compared to OLETF controls(P < 0.01). The serum glucose, insulin, HOMA-IR, and lipid profiles were also improved by ezetimibe(P < 0.05). In addition, autophagy-related m RNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3(LC3) were significantly increased in the liver in rats that received ezetimibe(P < 0.05). Likewise, for hepatocytes cultured in vitro, ezetimibe treatment significantly decreased PA-induced fat accumulation and increased PA-reduced m RNA and protein expression involved in autophagy(P < 0.05). Ezetimibe-increased autophagosomes was observed in TEM analysis. Immunoblotting analysis of autophagy formation with an inhibitor of autophagy demonstrated that ezetimibe-increased autophagy resulted from increased autophagic flux. CONCLUSION: The present study demonstrates that ezetimibe-mediated improvement in hepatic steatosis might involve the induction of autophagy.

Hepatic steatosis as a possible risk factor for the development of hepatocellular carcinoma after eradication of hepatitis C virus with antiviral therapy in patients with chronic hepatitis C

AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.

Hemodynamic changes in hepatic sinusoids of hepatic steatosis mice

BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the hemodynamics.AIM To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic steatosis.METHODS Eight-week-old male C57 BL/6 mice were divided into three groups randomly(control group, 2-wk group, and 4-wk group), with 16 mice per group. A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin(HE), and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids.RESULTS Oil red O staining indicated lipid accumulation in the liver after CCl_4 treatment.HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice onmorphological examination. Hemorheological tests included whole blood viscosity(mPas, γ = 10 s-1/γ = 100 s-1)(8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ±1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume(%)(51.00 ± 4.00, 42.00 ±5.00, and 40.00 ± 3.00), the content of plasma fibrinase(g/L)(3.80 ± 0.50, 2.90 ±0.80, and 2.30 ± 0.70), erythrocyte deformation index(%)(44.49 ± 5.81, 48.00 ±15.29, and 44.36 ± 15.01), erythrocyte electrophoresis rate(mm/s per V/m)(0.55 ±0.11, 0.50 ± 0.11, and 0.60 ± 0.20), revealing pathological changes in plasma components and red blood cells of hepatic steatosis. Assessment of blood flow velocity in the hepatic sinusoids with a laser Doppler flowmeter(mL/min per100 g)(94.43 ± 14.64, 80.00 ± 12.12, and 67.26 ± 5.92) and two-photon laser scanning microscope(μm/s)(325.68 ± 112.66, 213.53 ± 65.33, and 173.26 ± 44.02)revealed that as the modeling time increased, the blood flow velocity in the hepatic sinusoids decreased gradually, and the diameter of the hepatic sinusoids became smaller(μm)(10.28 ± 1.40, 6.84 ± 0.93, and 5.82 ± 0.79).CONCLUSION The inner diameter of the hepatic sinusoids decreases along with the decrease in the blood flow velocity within the sinusoids and the changes in the systemic hemorheology.

Adiponectin as a protective factor in hepatic steatosis

AIM: Obesity and insulin resistance (IR) are closely related to hepatic steatosis (HS), and adiponectin is a hepatic insulin sensitizer that has important effects in liver function. This study aims at investigating the relationship between serum adiponectin concentration and the presence of HS. METHODS: We carried out a cross-sectional study in a check-up unit of a University Hospital in Mexico City. We enrolled 196 subjects, comprising 98 subjects with HS (27 women, 71 men) and 98 controls (37 women and 61 men). Anthropometric, metabolic and biochemical variables were measured in the two groups. Serum adiponectin and leptin concentrations were determined, their association with grade of HS tested, and concentrations, according to quartiles, compared between cases and controls. X2 analysis for linear trends was used to test for a dose-response relationship and logistic regression analysis was conducted to test for a protective effect of adiponectin. RESULTS: The HS subjects were older and more obese than controls, with a central obesity pattern. In the fourth quartile of adiponectin concentrations, HS was less common and severe. In a multivariate model of the fourth quartile of the adiponectin concentrations, we observed a protective effect (OR = 0.17, 95%CI: 0.04-0.67, P= 0.01). In subjects with more severe HS, we observed higher leptin concentrations, and caloric intakes, total fat and iron consumption were higher than in controls. CONCLUSION: The results of the present study suggest that a high serum concentration of adiponectin is associated with a protective effect against HS.

Hepatic steatosis is associated with an increased risk of carotid atherosclerosis

AIM: Although an association between hepatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present study has been to investigate those relationships. METHODS: The Study of Health in Pomerania examined a random population sample aged between 20 and 79 years. A study population of 4 222 subjects without hepatitis B and C infections and without liver cirrhosis was available for the present analysis. Hepatic steatosis was defined sonographically and intima-media thickness (IMT) as well as plaque prevalence were estimated by carotid ultrasound. RESULTS: The prevalence rate of hepatic steatosis was 29.9%. Among subjects aged ≥45 years, an association between hepatic steatosis and IMT of the carotid arteries was found in bivariate analysis, but not after adjustment for atherosclerotic risk factors. Individuals with fatty liver had more often carotid plaques than persons without fatty liver (plaque prevalence rate 76.8% vs 66.6%; P<0.001). This association persisted after adjustment for confounding factors and was predominantly present in subjects with no to mild alcohol consumption. CONCLUSION: There is an independent association between hepatic steatosis and carotid atherosclerotic plaques. Metabolic changes due to nonalcoholic fatty liver disease may explain this relationship.

Chronic hepatitis B infection with concomitant hepatic steatosis:Current evidence and opinion

With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiologies,outcome,and mechanism of CHB with concomitant NAFLD have not been fully characterized.In this review,we assessed the overlapping prevalence of metabolic disorders and CHB,assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD,and discussed the remaining clinical issues to be addressed in the outcome of such patients.We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation.For CHB patients,it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses.The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.

Effects of resveratrol and other polyphenols in hepatic steatosis

Non-alcoholic fatty liver disease covers a wide spectrum of liver pathologies which range from simple steatosis to non-alcoholic steatohepatitis.Polyphenols are members of a very large family of plant-derived compounds that can have beneficial effects on human health,and thus their study has become an increasingly important area of human nutrition research.The aim of the present review is to compile published data concerning the effects of both isolated polyphenols as well as polyphenol extracts,on hepatocyte and liver fat accumulation under different steatosis-inducing conditions.The results reported clearly show that this group of biomolecules is able to reduce fat accumulation,but further studies are needed to establish the optimal dose and treatment period length.With regard to the potential mechanisms of action,there is a good consensus.The anti-lipidogenic effect of polyphenols is mainly due to reduced fatty acid and triacylglycerol synthesis,increased in fatty acid oxidation,and reduced of oxidative stress and inflammation.As a general conclusion,it can be stated that polyphenols are biomolecules which produce hepatoprotective effects.To date,these beneficial effects have been demonstrated in cultured cells and animal models.Thus,studies performed in humans are needed before these molecules can be considered as truly useful tools in the prevention of liver steatosis.

Non-invasive determination of hepatic steatosis by acoustic structure quantification from ultrasound echo amplitude

AIM:To use leptin-deficient(ob/ob) mice with demonstrated differences in steatosis levels to test a new diagnostic method using the acoustical structure quantification(ASQ) mode and the associated analytical parameter,"focal disturbance ratio"(FD-ratio).METHODS:Nine ob/ob mice,at 5,8,and 12 wk of age(n = 3 in each age group),were used as models for hepatic steatosis.Echo signals obtained from ultrasonography in the mice were analyzed by ASQ,which uses a statistical analysis of echo amplitude to estimate inhomogeneity in the diagnostic region.FD-ratio,as calculated from this analysis,was the focus of the present study.FD-ratio and fat droplet areas and sizes were compared between age groups.RESULTS:No fibrosis or inflammation was observed in any of the groups.The fat droplet area significantly(P < 0.01) increased with age from 1.25% ± 0.28% at 5 wk to 31.07% ± 0.48% at 8 wk to 51.69% ± 3.19% at 12 wk.The median fat droplet size also significantly(P < 0.01) increased with age,from 1.33(0.55-10.52) m at 5 wk,2.82(0.61-44.13) m at 8 wk and 6.34(0.66-81.83) m at 12 wk.The mean FD-ratio was 0.42 ± 0.11 at 5 wk,0.11 ± 0.05 at 8 wk,and 0.03 ± 0.02 at 12 wk.The FD-ratio was significantly lower at 12 wk than at 5 wk and 8 wk(P < 0.01).A significant negative correlation was observed between the FD-ratio and either the fat droplet area(r =-0.7211,P = 0.0017) or fat droplet size(r =-0.9811,P = 0.0052).CONCLUSION:This tool for statistical analysis of signals from ultrasonography using the FD-ratio can be used to accurately quantify fat in vivo in an animal model of hepatic steatosis,and may serve as a quantitative biomarker of hepatic steatosis.

MK-0626,a selective DPP-4 inhibitor,attenuates hepatic steatosis in ob/ob mice

AIM: To investigate the mechanism and in vivo effects of MK-0626, a dipeptidyl peptidase-4 inhibitor, on hepatic steatosis using ob/ob mice.

Hepatic steatosis and fibrosis: Non-invasive assessment

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.