Controlled attenuation parameter for evaluating liver steatosis in chronic viral hepatitis

AIM: To assess the performance of controlled attenuation parameter (CAP) in patients with chronic viral hepatitis.

Accurate and generalizable quantitative scoring of liver steatosis from ultrasound images via scalable deep learning

BACKGROUND Hepatic steatosis is a major cause of chronic liver disease.Two-dimensional(2D)ultrasound is the most widely used non-invasive tool for screening and monitoring,but associated diagnoses are highly subjective.AIM To develop a scalable deep learning(DL)algorithm for quantitative scoring of liver steatosis from 2D ultrasound images.METHODS Using multi-view ultrasound data from 3310 patients,19513 studies,and 228075 images from a retrospective cohort of patients received elastography,we trained a DL algorithm to diagnose steatosis stages(healthy,mild,moderate,or severe)from clinical ultrasound diagnoses.Performance was validated on two multiscanner unblinded and blinded(initially to DL developer)histology-proven cohorts(147 and 112 patients)with histopathology fatty cell percentage diagnoses and a subset with FibroScan diagnoses.We also quantified reliability across scanners and viewpoints.Results were evaluated using Bland-Altman and receiver operating characteristic(ROC)analysis.RESULTS The DL algorithm demonstrated repeatable measurements with a moderate number of images(three for each viewpoint)and high agreement across three premium ultrasound scanners.High diagnostic performance was observed across all viewpoints:Areas under the curve of the ROC to classify mild,moderate,and severe steatosis grades were 0.85,0.91,and 0.93,respectively.The DL algorithm outperformed or performed at least comparably to FibroScan control attenuation parameter(CAP)with statistically significant improvements for all levels on the unblinded histology-proven cohort and for“=severe”steatosis on the blinded histology-proven cohort.CONCLUSION The DL algorithm provides a reliable quantitative steatosis assessment across view and scanners on two multi-scanner cohorts.Diagnostic performance was high with comparable or better performance than the CAP.

Diagnostic value of controlled attenuation parameter for liver steatosis in patients with chronic hepatitis B

AIM: To study the diagnostic value of controlled attenuation parameter (CAP), evaluated by transient elastography, for liver steatosis in patients with chronic hepatitis B (CHB).

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.

Excess body weight, liver steatosis, and early fibrosis progression due to hepatitis C recurrence after liver transplantation

AIM: To investigate how weight gain after OLT affects the speed of fibrosis progression (SFP) during recurrent hepatitis C virus (HCV) infection of the graft.METHODS: Ninety consecutive patients (63 males,median age 53 years; 55 with HCV-related liver disease),transplanted at a single institution, were studied. All were followed for at least 2 years after OLT and had at least one follow-up graft biopsy, performed not earlier than 1 year after the transplant operation. For each biopsy, a single,experienced pathologist gave an estimate of both the staging according to Ishak and the degree of hepatic steatosis.The SFP was quantified in fibrosis units/month (FU/mo).The lipid metabolism status of patients was summarized by the plasma triglycerides/cholesterol (T/C) ratio. Body mass index (BMI) was measured before OLT, and 1 and 2 years after it.RESULTS: In the HCV positive group, the highest SFP was observed in the first post-OLT year. At that time point,a SFP ≤0.100 FU/mo was observed more frequently among recipients who had received their graft from a young donor and had a pre-transplant BMI value ＞26.0 kg/m2. At completion of the first post-transplant year, a BMI value ＞26.5 kg/m2 was associated with a T/C ratio ≤1. The proportion of patients with SFP ＞0.100 FU/mo descended in the following order: female recipients with a high T/C ratio, male recipients with high T/C ratio, and recipients of either gender with low T/C ratio. Hepatic steatosis was observed more frequently in recipients who, in the first post-transplant year, had increased their BMI ≥1.5 kg/m2 in comparison to the pre-transplant value. Hepatic steatosis was inversely associated with the staging score.CONCLUSION: Among HCV positive recipients, excessweight gain post-OLT does not represent a factor favoring early liver fibrosis development and might even be protective against it.

Severity of ultrasonographic liver steatosis and metabolic syndrome in Korean men and women

AIM：To evaluate the association between the severity of liver steatosis and metabolic syndrome in apparently healthy Korean adults. METHODS： We examined 1022 men and women, aged 30-79 years, who participated in a health screening test. A standard interview, anthropometrics, biochemical studies, and abdominal ultrasonography were conducted for each participant. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel Ⅲ, with a modification for the waist circumference cut-off level. The severity of liver steatosis was evaluated using liver ultrasonography, and serum aspartate aminotransferase（AST）, alanine aminotransferase （ALT）, and γ-glutamyl transferase （γ-GT） levels were determined. RESULTS： Ultrasonographic liver steatosis was strongly associated with metabolic syndrome and common metabolic abnormalities. Compared with people without steatosis, people with mild, moderate, and severe steatosis had adjusted odds ratios for metabolic syndrome of 2.72 （95% CI, 1.01-2.94）, 2.89 （1.75-4.76） and 3.53 （1.25-9.98） in men, and 2.86 （1.64-5.01）, 3.19 （1.80-5.65） and 3.70 （0.82-16.73） in women, respectively. The serum AST level was not associated with metabolic syndrome. The serum ALT and γ-GT levels were significantly associated with metabolic syndrome in men but not in women.CONCLUSION： The occurrence of metabolic syndrome shows a stronger association with the severity of ultrasonographic steatosis than with the serum liver enzyme levels. The degree of fatty infiltration detected on ultrasonography can be used as an indicator of liver dysfunction attributable to metabolic abnormalities.

Multiparametric ultrasound as a new concept of assessment of liver tissue damage

Liver disease accounts for approximately 2 million deaths per year worldwide.All chronic liver diseases(CLDs),whether of toxic,genetic,autoimmune,or infectious origin,undergo typical histological changes in the structure of the tissue.These changes may include the accumulation of extracellular matrix material,fats,triglycerides,or tissue scarring.Noninvasive methods for diagnosing CLD,such as conventional B-mode ultrasound(US),play a significant role in diagnosis.Doppler US,when coupled with B-mode US,can be helpful in evaluating the hemodynamics of hepatic vessels and detecting US findings associated with hepatic decompensation.US elastography can assess liver stiffness,serving as a surrogate marker for liver fibrosis.It is important to note that interpreting these values should not rely solely on a histological classification.Contrast-enhanced US(CEUS)provides valuable information on tissue perfusion and enables excellent differentiation between benign and malignant focal liver lesions.Clinical evaluation,the etiology of liver disease,and the patient current comorbidities all influence the interpretation of liver stiffness measurements.These measurements are most clinically relevant when interpreted as a probability of compensated advanced CLD.B-mode US offers a subjective estimation of fatty infiltration and has limited sensitivity for mild steatosis.The controlled attenuation parameter requires a dedicated device,and cutoff values are not clearly defined.Quan-titative US parameters for liver fat estimation include the attenuation coefficient,backscatter coefficient,and speed of sound.These parameters offer the advantage of providing fat quantification alongside B-mode evaluation and other US parameters.Multiparametric US(MPUS)of the liver introduces a new concept for complete noninvasive diagnosis.It encourages examiners to utilize the latest features of an US machine,including conventional B-mode,liver stiffness evaluation,fat quantification,dispersion imaging,Doppler US,and CEUS for focal liver lesion characterization.This comprehensive approach allows for diagnosis in a single examination,providing clinicians worldwide with a broader perspective and becoming a cornerstone in their diagnostic arsenal.MPUS,in the hands of skilled clinicians,becomes an invaluable predictive tool for diagnosing,staging,and monitoring CLD.

From non-alcoholic fatty liver disease to metabolic-associated steatotic liver disease:Rationale and implications for the new terminology

Non-alcoholic fatty liver disease(NAFLD)was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of alcohol.Alcoholic liver disease(ALD)has many similarities to NAFLD in both pathogenesis and histology.This entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of obesity.Attempts to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver disease.This new term,however,has the disadvantage of the use of terms that may be perceived as derogatory.The terms fatty and non-alcoholic have negative connotations in many cultures.In addition,non-alcoholic is not usually a term applicable to pediatric cases of hepatic steatosis.Recently,an international collaborative effort,with participants from 56 countries,after a global consultation process,recommended to change the nomenclature to steatotic liver disease-including metabolic dysfunction-associated steatotic liver disease,metabolic-associated steatohepatitis and metabolic dysfunction-associated ALD.The new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis,prognosis and treatment.

Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation

BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation.METHODS:Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis(MiS):MiS <30%(n=27), MiS 30%-60%(n=41) and MiS >60%(n=26).The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction(EAD) and primary nonfunction(PNF). RESULTS:The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF,one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group.CONCLUSION:Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.

F-box only protein 2 exacerbates non-alcoholic fatty liver disease by targeting the hydroxyl CoA dehydrogenase alpha subunit

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。

Effects of low molecular weight polysaccharide from Sargassum thunbergii against palmitic acid-induced intracellular lipid accumulation in 3T3-L1 adipocyte and HepG2 cells

Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunbergii and appraised their LMPST on palmitic acid(PA)induced lipid accretion in Hep G2,and 3T3-L1 cells.LMPST treatment lessened lipid deposition and intracellular free fatty acid and triglyceride intensities in PA-treated above mentioned cells.The mechanistic study publicized that LMPST2 significantly suppressed adipogenesis and stimulated the PA-treated 3T3-L1 cells occupied in the lipolysis pathway.Furthermore,in PA-treated Hep G2 cells,the free fatty acid oxidation was significantly increased by LMPST2.Given these constructive properties of LMPST2 from S.thunbergii,is a potential candidate for diminishing the intracellular lipids,and for a therapeutic agent in those conditions.

Radiologic evaluation of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD)is a frequent cause of chronic liver diseases,ranging from simple steatosis to nonalcoholic steatohepatitis(NASH)-related liver cirrhosis.Although liver biopsy is still the gold standard for the diagnosis of NAFLD,especially for the diagnosis of NASH,imaging methods have been increasingly accepted as noninvasive alternatives to liver biopsy.Ultrasonography is a well-established and costeffective imaging technique for the diagnosis of hepatic steatosis,especially for screening a large population at risk of NAFLD.Ultrasonography has a reasonable accuracy in detecting moderate-to-severe hepatic steatosis although it is less accurate for detecting mild hepatic steatosis,operator-dependent,and rather qualitative.Computed tomography is not appropriate for general population assessment of hepatic steatosis given its inaccuracy in detecting mild hepatic steatosis and potential radiation hazard.However,computed tomography may be effective in specific clinical situations,such as evaluation of donor candidates for hepatic transplantation.Magnetic resonance spectroscopy and magnetic resonance imaging are now regarded as the most accurate practical methods of measuring liver fat in clinical practice,especially for longitudinal followup of patients with NAFLD.Ultrasound elastography and magnetic resonance elastography are increasingly used to evaluate the degree of liver fibrosis in patients with NAFLD and to differentiate NASH from simple steatosis.This article will review current imaging methods used to evaluate hepatic steatosis,including the diagnostic accuracy,limitations,and practical applicability of each method.It will also briefly describe the potential role of elastography techniques in the evaluation of patients with NAFLD.

Olive oil consumption and non-alcoholic fatty liver disease

The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.

MicroRNAs as controlled systems and controllers in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is a multi-faceted condition including simple steatosis alone or associated with inflammation and ballooning(non-alcoholic steatohepatitis) and eventually fibrosis.The NAFLD incidence has increased over the last twenty years becoming the most frequent chronic liver disease in industrialized countries.Obesity,visceral adiposity,insulin resistance,and many other disorders that characterize metabolic syndrome are the major predisposing risk factors for NAFLD.Furthermore,different factors,including genetic background,epigenetic mechanisms and environmental factors,such as diet and physical exercise,contribute to NAFLD development and progression.Several lines of evidence demonstrate that specific microRNAs expression profiles are strongly associated with several pathological conditions including NAFLD.In NAFLD,microRNA deregulation in response to intrinsic genetic or epigenetic factors or environmental factors contributes to metabolic dysfunction.In this review we focused on microRNAs role both as controlled and controllers molecules in NAFLD development and/or their eventual value as non-invasive biomarkers of disease.

Efficacy and safety of moderately steatotic donor liver in transplantation

BACKGROUND: The discrepancy between available livers and requests for transplantation has forced many centers to use marginal donors in order to expand the donor pool. Many previous studies have demonstrated controversial results of the application of steatotic liver grafts. The aim of the present study was to summarize our experience and evaluate the value of steatotic liver grafts. METHODS: The clinical and follow-up data of 24 adult patients receiving moderately steatotic liver grafts (30%-60%) from May 2003 to June 2005 (group 1) were analyzed. After matching for age, gender, model for end-stage liver diseases score and cold ischemia time, another 24 patients receiving liver grafts with steatosis less than 30% were chosen as the control group (group 2). The patient and graft outcomes were compared between the two groups. RESULTS: No difference of liver and kidney functions in the first post-transplant week was found between the two groups (P > 0.05). Neither the incidence of early allograft dysfunction and acute kidney injury nor the patient survival rates (3 months, 6 months and 1 year) showed differences between groups 1 and 2 (P > 0.05). CONCLUSION: Moderately steatotic liver grafts provide adequate function in the first phase after transplantation and can be used for transplantation.

Weight loss interventions in living donor liver transplantation as a tool in expanding the donor pool: A systematic review and metaanalysis

BACKGROUND With increasing rates of liver transplantation and a stagnant donor pool,the annual wait list removals have remained high.Living donor liver transplantation(LDLT)is an established modality in expanding the donor pool and is the primary method of liver donation in large parts of the world.Marginal living donors,including those with hepatic steatosis,have been used to expand the donor pool.However,due to negative effects of steatosis on graft and recipient outcomes,current practice excludes overweight or obese donors with more than 10%macro vesicular steatosis.This has limited a potentially important source to help expand the donor pool.Weight loss is known to improve or resolve steatosis and rapid weight loss with short-term interventions have been used to convert marginal donors to low-risk donors in a small series of studies.There is,however,a lack of a consensus driven standardized approach to such interventions.AIM To assess the available data on using weight loss interventions in potential living liver donors with steatotic livers and investigated the feasibility,efficacy,and safety of using such donors on the donor,graft and recipient outcomes.The principal objective was to assess if using such treated donor livers,could help expand the donor pool.METHODS We performed a comprehensive literature review and meta-analysis on studies examining the role of short-term weight loss interventions in potential living liver donors with hepatic steatosis with the aim of increasing liver donation rates and improving donor,graft,and recipient outcomes.RESULTS A total of 6 studies with 102 potential donors were included.Most subjects were males(71).All studies showed a significant reduction in body mass index postintervention with a mean difference of-2.08(-3.06,1.10,I2=78%).A significant reduction or resolution of hepatic steatosis was seen in 93 of the 102(91.2%).Comparison of pre-and post-intervention liver biopsies showed a significant reduction in steatosis with a mean difference of-21.22(-27.02,-15.43,I2=56%).The liver donation rates post-intervention was 88.5(74.5,95.3,I2=42%).All donors who did not undergo LDLT had either recipient reasons or had fibrosis/steatohepatitis on post intervention biopsies.Post-operative biliary complications in the intervention group were not significantly different compared to controls with an odds ratio of 0.96[(0.14,6.69),I2=0].The overall post-operative donor,graft,and recipient outcomes in treated donors were not significantly different compared to donors with no steatosis.CONCLUSION Use of appropriate short term weight loss interventions in living liver donors is an effective tool in turning marginal donors to low-risk donors and therefore in expanding the donor pool.It is feasible and safe,with comparable donor,graft,and recipient outcomes,to non-obese donors.Larger future prospective studies are needed.

Biochemical determination of lipid content in hepatic steatosis by the Soxtec method

AIM:To establish a quantitative method to measure the amount of lipids.METHODS:The livers of 53 male Wistar rats(225 g) with different degrees of hepatic steatosis were studied.This model of hepatic steatosis was based on a high carbohydrate,fat-free modified diet.Biopsies were classified into four grades depending on fat accumulation,using the Kleiner and Brunt classification.Total fat was studied by the Soxtec method(SoxtecTM 2050 Auto Fat Extraction System),and agreement between both assays was assessed by calculating theκ coefficient.RESULTS:According to the histological classification,38% of rats presented grade 0,21% grade 1,22% grade 2 and 20% grade 3.The amount of fat per 100 g tissue was 2.60±0.64 g for grade 0,3.87±1.59 g for grade 1,5.82±1.37 g for grade 2 and 8.68± 2.30 g for grade 3.Statistically significant differences were found between the mean values for each of the histological grades(P<0.05).The correlation for the quantification of fat in the liver between both assays was moderate(κ=0.60).CONCLUSION:The biochemical quantification of fat in liver tissue by the Soxtec method was correlated with the histological classification,although the agreement between the two tests was only moderate.

Moro orange juice prevents fatty liver in mice

AIM:To establish if the juice of Moro,an anthocyaninrich orange,may improve liver damage in mice with diet-induced obesity.METHODS:Eight-week-old mice were fed a high-fat diet(HFD) and were administrated water or Moro juice for 12 wk.Liver morphology,gene expression of lipid transcription factors,and metabolic enzymes were assessed.RESULTS:Mice fed HFD displayed increased body weight,insulin resistance and dyslipidemia.Moro juice administration limited body weight gain,enhanced insulin sensitivity,and decreased serum triglycerides and total cholesterol.Mice fed HFD showed liver steatosis associated with ballooning.Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase,a key enzyme of lipid oxidation.Consistently,Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase,and restored liver glycerol-3-phosphate acyltransferase 1 activity.CONCLUSION:Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.

Effect of dietary supplementation with olive and sunflower oils on lipid profile and liver histology in rats fed high cholesterol diet

Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil(cholesterol free diet) and 1% HC containing 12% olive oil(HC+OO) enriched with MUFA and 12% sunflower oil(HC+SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. Results: Comparatively, rats treated with HC+OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC+SO diet(P<0.05). Otherwise, HC+OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1. Conclusions: HC+OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC+SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC+OO diet can be caused by the delay in the FA release to the blood.

Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and effective treatments are still lacking.Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome,and higher hepatic iron and fat content.Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD,and iron depletion reduced insulin resistance and liver enzymes.Recently,Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD,and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis.These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD,and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients.