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.

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.

Factors Associated with Hepatic Steatosis in Black African Subjects with Chronic Viral Hepatitis B in Côte d’Ivoire

Context/Objectives: With the progression of the global epidemic of obesity and metabolic syndrome, the coexistence of hepatic steatosis in patients with chronic viral hepatitis B (VHB) is becoming significant. The aim of this work was to determine the factors associated with hepatic steatosis assessed by a Fibroscan with Controlled Attenuation Parameter (CAP) in patients with chronic viral hepatitis B in Côte d’Ivoire. Methods: This was a cross-sectional and analytical study. Data was collected from February 15 to July 31, 2020 in a private hospital structure in the city of Abidjan in Côte d’Ivoire. We included 83 patients with chronic viral hepatitis B. These were black patients, having performed a Fibroscan/CAP during the recruitment period and consenting to participate in the study. Patients with significant alcohol consumption, a secondary cause of hepatic steatosis, or other liver disease regardless of the etiology associated with hepatitis B were not included. Results: The frequency of hepatic steatosis in chronic VHB carriers assessed by the CAP in our study population was 48.19% including 24.10% severe steatosis. Obesity and high LDL cholesterol were statistically correlated with the presence of steatosis in our patients. Patients who had steatosis on ultrasound were 5 times more likely to have steatosis on CAP. Significant fibrosis was not significantly associated with steatosis. Conclusion: Obesity and LDL hypercholesterolemia are the main factors associated with hepatic steatosis detected by Fibroscan/CAP in patients with chronic viral hepatitis B.

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.

Sodium butyrate alleviates fructose-induced non-alcoholic fatty liver disease by remodeling gut microbiota to promoteγ-amino butyric acid production

Sodium butyrate(NaB)can regulate lipid metabolism and inhibit hepatic steatosis.This study aimed to investigate whether NaB can alleviate fructose-induced hepat ic steatosis via remodeling the gut microbiota and evaluate the anti-fatty liver mechanisms.The results showed that NaB and NaB-remodeled gut microbiota significantly alleviated fructose-induced hepatic steatosis and increased plasma uric acid and fructose levels.Furthermore,both NaB and NaB-remodeled gut microbiota increased the abundance of Lactobacillus and altered the levels of plasma amino acids(upregulating gamma-amino butyric acid(GABA)and downregulating L-glutamic acid and L-arginine)in fructose-exposed mice.The correlation analysis showed that GABA levels positively correlated with Lactobacillus abundance,and increased GABA levels might promote the reduction of the hepatic triglyceride content.Further studies confirmed that GABA significantly reduced lipid deposition in mouse hepatocytes induced via fructose pretreatment in vitro.These findings suggested that NaB could ameliorate fructose-induced hepatic steatosis by regulating gut microbiota.

Perilipin 2 inhibits replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions

Hepatitis B virus(HBV)infection poses a global health concern without a definitive cure;however,antiviral medications can effectively suppress viral replication.This study delves into the intricate interplay between lipid metabo-lism and HBV replication,implicating molecular mechanisms such as the stearoyl coenzyme A desaturase 1 autophagy pathway,SAC1-like phosphatidylinositol phosphatase,and galectin-9 mediated selective autophagy of viral core proteins in regulating HBV replication.Within lipid droplets,perilipin 2(PLIN2)emerges as a pivotal guardian,with its overexpression protecting against autophagy and downregulation stimulating triglyceride catabolism through the autophagy pathway.This editorial discusses the correlation between hepatic steatosis and HBV replication,emphasizing the role of PLIN2 in this process.The study underscores the multifaceted roles of lipid metabolism,autophagy,and perilipins in HBV replication,shedding light on potential therapeutic avenues.

Prospective study comparing hepatic steatosis assessment by magnetic resonance imaging and four ultrasound methods in 105 successive patients

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is becoming a major health problem,resulting in hepatic,metabolic and cardio-vascular morbidity.AIM To evaluate new ultrasonographic tools to detect and measure hepatic steatosis.METHODS We prospectively included 105 patients referred to our liver unit for NAFLD suspicion or follow-up.They underwent ultrasonographic measurement of liver sound speed estimation(SSE)and attenuation coefficient(AC)using Aixplorer MACH 30(Supersonic Imagine,France),continuous controlled attenuation parameter(cCAP)using Fibroscan(Echosens,France)and standard liver ultrasound with hepato-renal index(HRI)calculation.Hepatic steatosis was then classified according to magnetic resonance imaging proton density fat fraction(PDFF).Receiver operating curve(ROC)analysis was performed to evaluate the diagnostic performance in the diagnosis of steatosis.RESULTS Most patients were overweight or obese(90%)and had metabolic syndrome(70%).One third suffered from diabetes.Steatosis was identified in 85 patients(81%)according to PDFF.Twenty-one patients(20%)had advanced liver disease.SSE,AC,cCAP and HRI correlated with PDFF,with respective Spearman correlation coefficient of-0.39,0.42,0.54 and 0.59(P<0.01).Area under the receiver operating characteristic curve(AUROC)for detection of steatosis with HRI was 0.91(0.83-0.99),with the best cut-off value being 1.3(Se=83%,Sp=98%).The optimal cCAP threshold of 275 dB/m,corresponding to the recent EASL-suggested threshold,had a sensitivity of 72%and a specificity of 80%.Corresponding AUROC was 0.79(0.66-0.92).The diagnostic accuracy of cCAP was more reliable when standard deviation was<15 dB/m with an AUC of 0.91(0.83-0.98).An AC threshold of 0.42 dB/cm/MHz had an AUROC was 0.82(0.70-0.93).SSE performed moderately with an AUROC of 0.73(0.62-0.84).CONCLUSION Among all ultrasonographic tools evaluated in this study,including new-generation tools such as cCAP and SSE,HRI had the best performance.It is also the simplest and most available method as most ultrasound scans are equipped with this module.

Theasinensin A attenuated diabetic development by restoring glucose homeostasis, improving hepatic steatosis and modulating gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice

Theasinensin A(TSA),a dimer of epigallocatechin gallate,has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects.However,little information is available on its potential mechanisms of anti-diabetes.Therefore,the present study aimed to investigate the influence of TSA on glucose and lipid metabolism and gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice.As result,TSA improved polydipsia,polyphagia and impaired glucose tolerance of diabetic mice,declined the fasting blood glucose and hepatic triglyceride level,and enhanced the expression at mRNA level of insulin receptor substrate,phosphoinositide 3-kinase,protein kinase B and glucagon-like peptide 1 receptor(GLP-1R)in the diabetic liver.Moreover,TSA could restore the disorder of gut microbiota of diabetic mice.High-dose(100 mg/kg)TSA showed better benefi cial effects from the blood biochemical parameters,hepatic function and gut microbiota.In general,high-dose TSA significantly modulated gut microbiota by increasing the relative abundance of Akkermansia and decreasing the relative abundances of Acetatifactor,Anaerotruncus,Pseudofl avonifactor,Oscillibacter and Clostridium clusters.The results indicated that TSA could exert an anti-diabetes effect in diabetic mice through restoring glucose homeostasis,declining hepatic steatosis,activating insulin and GLP-1 signaling pathways,and ameliorating gut microbiota dysbiosis.

Prevalence and Factors Associated with Hepatic Steatosis in Patients with Metabolic Syndrome in Cameroon: Cases of 4 Reference Hospitals

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide and its prevalence increases with that of metabolic syndrome and its components. NAFLD is associated with complications such as cirrhosis and hepatocellular carcinoma. Diagnosis is mainly based on liver biopsy, but there are validated non-invasive methods. The purpose of the study was to assess the impact of metabolic steatopathy in patients with metabolic syndrome in Cameroon. Methods: This was a cross-sectional and analytical study conducted over a 6-month period from January 1st, 2019, to August 31st, 2022. Included were patients with metabolic syndrome who had consulted in endocrinology or gastroenterology at Yaoundé Central Hospital, Douala General Hospital and Douala Gyneco-obstetric and Pediatric Hospital. The diagnosis of NAFLD was made on abdominal ultrasound in front of a homogeneous or heterogeneous hyperechogenic aspect of the hepatic parenchyma compared to that of the right renal cortex called “brilliant liver” and fibrosis evaluated through non-invasive scores (Fib4 and NALFD Fibrosis score). Logistic regression by a uni- and multivariate analysis made it possible to search for the associated factors. Results. We included 133 patients. The female sex represented 64.7%. The mean age was 55 ± 9 years. The prevalence of NAFLD was 48.9%. At the evaluation of fibrosis was significant according to FIB-4 and NAFLD fibrosis score respectively in 6.2% and 4.6% of cases. The independently associated factors were Triglyceridemia ≤ 1.5 g/l (OR = 0.33;95% CI [0.11 - 0.95];p = 0.04) and LDL hypercholesterolemia (OR = 2.94;95% CI [1.07 - 8.11];p = 0.036). Conclusion: NAFLD was present in almost half of patients with metabolic syndrome. We had very few patients with significant fibrosis, but it needs to be further evaluated. The associated factors are hypertriglyceridemia and LDL hypercholesterolemia.

Two-point Dixon and six-point Dixon magnetic resonance techniques in the detection,quantification and grading of hepatic steatosis

BACKGROUND Hepatic steatosis is a very common problem worldwide.AIM To assess the performance of two-and six-point Dixon magnetic resonance(MR)techniques in the detection,quantification and grading of hepatic steatosis.METHODS A single-center retrospective study was performed in 62 patients with suspected parenchymal liver disease.MR sequences included two-point Dixon,six-point Dixon,MR spectroscopy(MRS)and MR elastography.Fat fraction(FF)estimates on the Dixon techniques were compared to the MRS-proton density FF(PDFF).Statistical tests used included Pearson’s correlation and receiver operating characteristic.RESULTS FF estimates on the Dixon techniques showed excellent correlation(≥0.95)with MRS-PDFF,and excellent accuracy[area under the receiver operating characteristic(AUROC)≥0.95]in:(1)Detecting steatosis;and(2)Grading severe steatosis,(P<0.001).In iron overload,two-point Dixon was not evaluable due to confounding T2*effects.FF estimates on six-point Dixon vs MRS-PDFF showed a moderate correlation(0.82)in iron overload vs an excellent correlation(0.97)without iron overload,(P<0.03).The accuracy of six-point Dixon in grading mild steatosis improved(AUROC:0.59 to 0.99)when iron overload cases were excluded.The excellent correlation(>0.9)between the Dixon techniques vs MRSPDFF did not change in the presence of liver fibrosis(P<0.01).CONCLUSION Dixon techniques performed satisfactorily for the evaluation of hepatic steatosis but with exceptions.

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.

Targeting Kupffer cells in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Why and how?

Mechanisms for non-alcoholic steatohepatitis(NASH)development are under investigation in an era of increased prevalence of obesity and metabolic syndrome. Previous findings have pointed to the role of adipose tissue, adipose tissue macrophages and their secretory products in the development of a chronic inflammatory status inducing insulin resistance and a higher risk of liver steatosis called non-alcoholic fatty liver disease. The activation of resident macrophages [Kupffer cells(KC)] and the recruitment of blood derived monocytes/macrophages into the diseased liver have now been identified as key elements for disease initiation and progression. Those cells could be activated through gut flora modifications and an altered gut barrier function but also through the internalization of toxic lipid compounds in adjacent hepatocytes or in KC themselves. Due to the role of activated KC in insulin resistance, fibrosis development and inflammation amplification, they became a target in clinical trials. A shift towards an anti-inflammatory KC phenotype through peroxisome proliferator activator-receptorδ agonists, an inhibition of macrophage recruitment through anti-C-C chemokine receptor 2 action and a specific blocking of internalization of toxic lipoxidation or glycation compounds into KC by galectin-3 receptor inhibitors are now under investigation in human NASH.

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.

TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype

AIM To evaluate the impact of the Glu167Lys(E167K) transmembrane 6 superfamily member 2(TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infected patients.METHODS The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K(rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males(73.6%), the median age was 40.7 years and the immunological condition good(median CD4+ cells/mm3 = 505.5).RESULTS The 17 patients with the TM6SF2 E167 K variant, compared with the 150 with TM6SF2-E/E, showed higher AST(P = 0.02) and alanine aminotransferase(P = 0.02) and higher fibrosis score(3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167 K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167 K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCVgenotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167 K in non-3 HCV genotypes. No association between the TM6SF2 E167 K variant and severe liver necroinflammation was observed.CONCLUSION In HIV/HCV coinfection the TM6SF2 E167 K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype.

CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

AIM: To determine intra-hepatic blood flow and liver stiffness in patients with non-alcoholic fatty liver disease(NAFLD) and non-alcoholic steatohepatitis (NASH) using contrast-enhanced ultrasound and fibroscan.METHODS: This prospective study included 15 patients with NAFLD, 17 patients with NASH and 16 healthy controls.In each patient, real-time ultrasound was used to locate the portal vein (PV) and the right liver lobe, and 5 mL of SonoVue? was then injected intravenous in a peripheral vein of the left arm over a 4-s span. Digital recording was performed for 3 min thereafter. The recording was subsequently retrieved to identify an area of interest in the PV area and in the right liver parenchyma(LP) to assess the blood flow by processing the data using dedicated software (Qontrast?, Bracco, Italy).The following parameters were evaluated: percentage of maximal contrast activity (Peak%), time to peak (TTP, s), regional blood volume (RBV, cm3), regional blood flow (RBF, cm3/s) and mean transit time (MTT, s).At 24-48 h post-injection, liver stiffness was evaluated using Fibroscan and measured in kPa. The statistical evaluation was performed using Student’s t test.RESULTS: In the PV, the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patientscompared with the controls (Peak%: NAFLD 26.3 ± 6.6,NASH 28.1 ± 7.3 vs controls 55.8 ± 9.9, P < 0.001;RBV: NAFLD 4202.3 ± 3519.7, NASH 3929.8 ± 1941.3vs controls 7473 ± 3281, P < 0.01; RBF: NAFLD 32.5± 10.8, NASH 32.7 ± 12.1 vs controls 73.1 ± 13.9, P< 0.001). The TTP in the PV was longer in both patient groups but reached statistical significance only in the NASH patients compared with the controls (NASH 79.5± 37.8 vs controls 43.2 ± 30, P < 0.01). In the LP,the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patients compared with the controls (Peak%: NAFLD 43.2 ± 7.3, NASH 41.7 ± 7.7 vs controls 56.6 ± 6.3, P < 0.001; RBV: NAFLD 4851.5± 2009, NASH 5069.4 ± 2292.5 vs controls 6922.9 ±2461.5, P < 0.05; RBF: NAFLD 55.7 ± 10.1, NASH 54.5 ± 12.1 vs controls 75.9 ± 10.5, P < 0.001). The TTP was longer in both patient groups but did not reach statistical significance. The MTT in both the PV and LP in the NAFLD and NASH patients was not different from that in the controls. Liver stiffness was significantly increased relative to the controls only in the NASH patients(NASH: 6.4 ± 2.2 vs controls 4.6 ± 1.5, P < 0.05).CONCLUSION: Blood flow derangement within the liver present not only in NASH but also in NAFLD suggests that a vascular flow alteration precedes liver fibrosis development.

Liver steatosis in hepatitis C patients

There is controversy regarding some aspects of hepatitis C virus(HCV) infection-associated liver steatosis,and their relationship with body fat stores. It has classically been found that HCV,especially genotype 3,exerts direct metabolic effects which lead to liver steatosis. This supports the existence of a so called viral steatosis and a metabolic steatosis,whichwould affect HCV patients who are also obese or diabetics. In fact,several genotypes exert metabolic effects which overlap with some of those observed in the metabolic syndrome. In this review we will analyse the pathogenic pathways involved in the development of steatosis in HCV patients. Several cytokines and adipokines also become activated and are involved in "pure" steatosic effects,in addition to inflammation. They are probably responsible for the evolution of simple steatosis to steatohepatitis,making it difficult to explain why such alterations only affect a proportion of steatosic patients.

Steatosis and steatohepatitis in postmortem material from Northwestern Greece

AIM: To determine the prevalence of steatosis and steatohepatitis in a series of autopsies in Northwestern Greece. METHODS: Liver biopsy material from a total of 600 autopsies performed over a period of 2 years (2006-2008) to def ine the cause of death was subjected to histological examination. Patient demographic data were also collected. Tissue sections were stained with different dyes for the evaluation of liver architecture, degree of fibrosis and other pathological conditions when necessary. RESULTS: Satisfactory tissue samples for histological evaluation were available in 498 cases (341 male, 157 female) with a mean age of 64.51 ± 17.78 years. In total, 144 (28.9%) had normal liver histology, 156 (31.3%) had evidence of steatosis, and 198 (39.8%) had typical histological findings of steatohepatitis. The most common causes of death were ischemic heart disease with or without myocardial infarction (43.4%), and traffic accidents (13.4%). CONCLUSION: A high prevalence of steatosis and steatohepatitis was detected in postmortem biopsies from Northwestern Greece. Since both diseases can have serious clinical consequences, they should be considered as an important threat to the health of the general population in Greece.

Impact of liver steatosis on response to pegylated interferon therapy in patients with chronic hepatitis B

AIM: To evaluate the impact of liver steatosis upon response to given therapy in chronic hepatitis B (CHB) patients. METHODS: 84 consecutive CHB patients treated with 48-wk PEGylated interferon (PEG-IFN) therapy were enrolled. Baseline characteristics and sustained viral response (SVR) to PEG-IFN therapy were evaluated. RESULTS:Mean body mass index (BMI) was 27.36 ± 4.4 kg/m 2 . Six (7.1%) had hypertension and three (3.5%) had diabetes mellitus. Steatosis was present in 22.6% (19/84) of liver biopsy samples. Age, BMI, and triglyceride levels of the patients with hepatic steatosis were significantly higher than those without hepatic steatosis (P < 0.05). SVR to PEG-IFN therapy was 21.4% (18/84). Sixteen of these 18 CHB patients with SVR (88.9%) did not have any histopathologically determined steatosis. On the other hand, only two of the 19 CHB patients with hepatic steatosis had SVR (10.5%). Although the SVR rate observed in patients without steatosis (16/65, 24.6%) was higher compared to those with steatosis (2/19, 10.5%), the difference was not statistically significant (P > 0.05). CONCLUSION:Occurrence of hepatic steatosis is significantly high in CHB patients and this association leads to a trend of decreased, but statistically insignificant, SVR rates to PEG-IFN treatment.

Adipokines,cytokines and body fat stores in hepatitis Cvirus liver steatosis

AIM: To identify patients with or without liver steatosis and its severity in treatment-na?ve patients affected by hepatitis C virus(HCV) infection.METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body(by densitometry), hormones [insulin, homeostatic model assessment(HOMA)], adipokines(resistin, adiponectin, leptin), and cytokines(tumor necrosis factor α, interleukin-6).RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunkfat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin.CONCLUSION: Steatosis in HCV infection is common(67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

Steatosis and insulin resistance in hepatitis C: A way out for the virus?

The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.