7-9 Their ex vivo monocyte responses to LPS are significantly

7-9 Their ex vivo monocyte responses to LPS are significantly

enhanced relative to controls and this LPS hyperresponsiveness can be reproduced in vitro by exposure of the human macrophage cell line MonoMac6 to ethanol for 6 days.10 The enhanced and sustained inflammatory response seen in AAH is, however, in complete contradistinction to the normal processing of portal endotoxin by the liver.11 The liver is normally subject to tonic endotoxin exposure by way of the portal vein and it is effective at clearing this endotoxin from the blood without an inflammatory response. The phenomenon of “endotoxin tolerance” thereby renders endotoxin-exposed Kupffer cells refractory to further LPS stimulation, maintaining an anti- rather than proinflammatory cytokine output.12 Selleckchem Fostamatinib It is therefore somewhat unexpected that the proinflammatory response to endotoxin in AAH should be so disproportionately high, particularly considering that it is the Kupffer cells themselves that are key to maintaining hepatic endotoxin tolerance.13 It has become increasingly clear, therefore, that the enhancement of cytokine gene expression and perpetuation of the inflammatory response

is the key event in the pathogenesis of AAH.14 Despite its clear importance for the pathogenesis of AAH, the mechanism for enhanced inflammatory cytokine release in this disease remains unclear. In this study we address the novel hypothesis that the enhanced inflammatory cytokine response results from the direct actions of ethanol itself on the final common pathway of cytokine gene transcriptional Compound Library manufacturer regulation by histone acetylation. In its untranscribed state DNA is tightly coiled around histone protein octamers and the resulting chromatin is compacted into a closed tertiary structure from which the histone tails protrude, but in which the DNA is inaccessible to polymerases

Akt inhibitor involved in gene transcription. Gene activation by transcription factors involves coactivator proteins with histone acetyl transferase (HAT) activity that acetylate key lysine residues in the histone tails. The negatively charged acetyl groups cause a conformational change in chromatin that allows RNA polymerases access to the DNA, facilitating gene transcription. Termination of transcription is mediated through histone deacetylases (HDAC), which release free acetate and allow the chromatin to resume its closed, untranscribed conformation.15 Various HDACs are able to modulate inflammatory gene transcription, including class I and II HDACs, which can be recruited by transcriptional repressors such as the activated glucocorticoid receptor and class III HDACs, known as sirtuins (SIRT), which are active in the presence of nicotinamide adenine dinucleotide (NAD+).16 Ethanol has been demonstrated to increase total histone acetylation in rat liver17 with increased HAT and reduced HDAC activity18 and separate investigations have established that both SIRT expression and activity can be inhibited by ethanol in the liver.

Beyond the regulation of bile acid synthesis, FXR improves insuli

Beyond the regulation of bile acid synthesis, FXR improves insulin sensitivity and glucose uptake in adipose tissue, and the liver and the skeletal muscle, by regulating metabolic genes such as PEPCK, G6Pase, and FBP1.[86] Moreover, FXR suppresses pro-inflammatory genes like interferon γ, tumor necrosis factor-α, see more and interleukin-6 by affecting NFkappaB transcriptional activity.[86, 87] However, this broad spectrum is likely to result in adverse side effects, and selective FXR agonists are required to mainly alter gene expression relevant to NASH and insulin resistance. In the MCD model of steatohepatitis, WAY-362450,

a synthetic FXR ligand, protected against hepatic inflammation and fibrosis without inhibiting hepatic triglyceride accumulation.[88] this website Currently, obeticholic acid, a semi-synthetic bile acid derivative, is tested in patients with biopsy-proven NASH (ClinicalTrials.gov Identifier: NCT01265498).[86] An unwanted side effect of obeticholic acid is exacerbation of itching. A pro-inflammatory intestinal microbiome has been observed in mice and patients with NASH.[37-39, 41] In a model of genetic dyslipidemia

using ApoE-deficient mice, supplementation of the probiotic VSL#3 that contains different lactobacilli and bifidobacteria improved insulin signaling in hepatocytes and ameliorated adipose tissue inflammation,[89] and the supplementation of lactobacillus casei shirota protected Chloroambucil mice from increased activation of TLR4 and hepatic steatosis induced by a high-fructose diet.[90] In an open-label pilot study in 20 patients with biopsy-proven NASH, supplementation of a probiotic containing lactobacilli and bifidobacteria

over 6 months improved hepatic steatosis, as determined by MRI and serum transaminases.[91] Together with the human randomized controlled study on fecal transplantation of a healthy microbiota in patients with insulin resistance,[42] these recent reports support the role of microbiota in the pathogenesis of insulin resistance and NASH, partly by reducing bacterial inflammatory triggers and nutrient extractions and modification. It also hints to a role of prebiotics, that is nutrients that favor the growth of certain bacterial species, that may likely play in the treatment of obesity and NASH.[92] NAFLD has become a global challenge to our health-care systems. Changes in lifestyle and nutrition have put large parts of the population at risk of developing NASH, cirrhosis, and liver cancer. In contrast to other liver diseases with emerging therapeutic options, and despite the benefit of lifestyle changes, NAFLD will remain a great health problem necessitating (adjunctive) pharmacological therapies. Moreover, given the unpredictable course of this common disease, improved non-invasive biomarkers are urgently needed to better assess NAFLD/NASH activity and fibrosis, and to speed up drug development.

These

These GSI-IX cost results have important implications for the development of antibody-based therapies against HBV. “
“Background and Aim:  Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma

(HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies. Methods:  The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor β-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined. Results:  LH86 cells display epithelial morphology. Transforming-growth-factor-β-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth-factor-induced mesenchymal changes in them were

associated with loss of E-cadherin, albumin, α-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin

E2 (PGE2), Akt and phosphorylated Selleckchem Metformin Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT. Conclusions:  Multiple growth factors induce EMT in HCC. COX-2 Immune system and Akt may mediate EMT-associated development and progression of HCC and molecular targeting of COX-2 and Akt may be an effective therapeutic or chemopreventive strategy in advanced and metastatic HCC. “
“In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35 years and those aged 35 years or older.

These th

These Metformin results have important implications for the development of antibody-based therapies against HBV. “
“Background and Aim:  Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma

(HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies. Methods:  The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor β-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined. Results:  LH86 cells display epithelial morphology. Transforming-growth-factor-β-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth-factor-induced mesenchymal changes in them were

associated with loss of E-cadherin, albumin, α-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin

E2 (PGE2), Akt and phosphorylated Sirolimus price Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT. Conclusions:  Multiple growth factors induce EMT in HCC. COX-2 www.selleck.co.jp/products/Gemcitabine(Gemzar).html and Akt may mediate EMT-associated development and progression of HCC and molecular targeting of COX-2 and Akt may be an effective therapeutic or chemopreventive strategy in advanced and metastatic HCC. “
“In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35 years and those aged 35 years or older.

These C

These Idasanutlin in vitro results have important implications for the development of antibody-based therapies against HBV. “
“Background and Aim:  Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma

(HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies. Methods:  The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor β-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined. Results:  LH86 cells display epithelial morphology. Transforming-growth-factor-β-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth-factor-induced mesenchymal changes in them were

associated with loss of E-cadherin, albumin, α-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin

E2 (PGE2), Akt and phosphorylated selleck screening library Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT. Conclusions:  Multiple growth factors induce EMT in HCC. COX-2 Microbiology inhibitor and Akt may mediate EMT-associated development and progression of HCC and molecular targeting of COX-2 and Akt may be an effective therapeutic or chemopreventive strategy in advanced and metastatic HCC. “
“In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35 years and those aged 35 years or older.

apoB-100, apolipoprotein B-100; ANOVA, analysis of variance; ASGP

apoB-100, apolipoprotein B-100; ANOVA, analysis of variance; ASGPR1, asialoglycoprotein receptor; CAD, coronary artery disease; FH, familial hypercholesterolemia; FL-LDL, fluorescently labeled LDL; GWAS, genome-wide association studies; hESC, human embryonic stem cell; hiPSC, human induced pluripotent stem cell; HMG-CoA, 3-hydroxy-3-methyl-glutaryl-coenzyme A; HNF4a, hepatocyte nuclear factor 4a; iPSC, induced pluripotent stem cell; LDL-C, low-density lipoprotein cholesterol; LY294002 mRNA, messenger RNA; qRT-PCR, quantitative reverse-transcription polymerase chain reaction; SREBP, sterol regulatory element binding protein; VLDL, very low-density lipoprotein. A detailed description

of the Materials and Methods is provided in the Supporting Information. Procedures used for the generation of iPSCs and differentiation of pluripotent stem cells to hepatocytes have been described.4, 9 All culture of human embryonic stem cells (hESCs) and generation of iPSCs was approved by the MCW Human Stem Cell

Research Oversight Committee (hSCRO approval #09-005), and all animal procedures were approved by the Medical College of Wisconsin’s Institutional Animal Care and Use Committee. FH is an autosomal dominant dyslipidemia caused by mutations in the LDLR gene that result in severely elevated plasma LDL-C levels and premature cardiovascular disease.10 The liver is central to the pathogenesis of FH, and homozygous FH patients are selleck products successfully treated with liver transplantation. Although

hepatocytes are the key cells that control cholesterol flux, LDLR mutations have primarily been studied using fibroblasts.10 Such studies Orotidine 5′-phosphate decarboxylase revealed that LDLR-deficient fibroblasts had an impaired capacity to internalize LDL, which gave rise to the paradigm that the level of LDL-C in serum is determined by the rate of LDL clearance.11 However, modifications to this model have recently been proposed based on evidence suggesting that FH patients often possess profoundly elevated hepatic very low-density lipoprotein (VLDL) production.12 Given the extensive understanding of FH and the fact that single nucleotide polymorphisms have been identified in the vicinity of the LDLR gene, we felt that hepatocytes derived from FH hiPSCs would offer an ideal model to define the feasibility of using iPSCs to study genetic variations that could affect complex hepatic metabolism. The generation of iPSCs from a patient with early onset atherosclerotic disease with hypercholesterolemia has been described7; however, the genetic lesion was undefined. In addition, this study by Rashid et al. was designed only to test whether cells derived from LDLR-deficient iPSCs could internalize LDL. However, LDLR-mediated uptake of LDL is not a hepatocyte-specific process, and most cells use this pathway to internalize cholesterol.

2 NKT cells are abundant in the liver They recognize lipid antig

2 NKT cells are abundant in the liver. They recognize lipid antigens presented by CD1d and had different roles in liver diseases. NKT cells produce a wide range of cytokines promptly after activation.23 It is well accepted that Th1 cytokines suppress fibrosis, whereas Th2 cytokines promote fibrosis.24 In wildtype (WT) mice, it was reported that NKT cells can suppress the activation of HSC.22 But in different animal models and in human patients the conclusions were controversial.25, 26 Although the acceleration of HBV infection to liver fibrosis Selleckchem Barasertib have been extensively observed in clinical settings,

the immune response during this process is not clear, especially in the condition of the HBV carriers with no obvious symptoms. In this study, by using HBV transgenic mice (HBV-tg) that mimic human HBV healthy carriers,27 we found liver fibrosis spontaneously occurred in old age of HBV-tg mice, and, importantly, CAL-101 mw HBV-tg mice were much more sensitive to the hepatotoxin CCl4-induced liver injury and liver fibrosis with the accompanied overactivation of HSCs. Further study demonstrated

that hepatic NKT cells from HBV-tg mice could directly activate HSCs and thereafter induce liver fibrosis in the experiments of cellular depletion and adoptive transfer, and IL-4 and IL-13 secreted by NKT cells were considered a crucial step for the activation of HSCs. α-SMA: α smooth muscle actin; CCl4: carbon tetrachloride; ECM: extracellular matrix; HBV: hepatitis B virus; HBV-tg: HBV transgenic mice; HSC: hepatic stellate cells; IFN-γ, interferon gamma; IL: interleukin; MMP: matrix metalloproteinase; MNC: mononuclear cell; mRNA: messenger RNA; NKT, natural killer T; qPCR: quantitative polymerase chain reaction; TIMP: tissue inhibitor of metalloproteinase. ifenprodil HBV transgenic mice C57BL/6J-TgN (AlblHBV) 44Bri, which contains HBV genome S, pre-S, and X domains, were purchased from VITALRIVER experiment animal company (Beijing, China), who obtained the animals from Jackson Laboratory

(Bar Harbor, ME). C57BL/6 mice were also purchased from VITALRIVER experiment animal company. Rag1−/− mice were purchased from Model Animal Research Center (Nanjing, China), who obtained the mice from Jackson Laboratory. Mice were housed in a specific pathogen-free facility and used according to the regulations of animal care of University of Science and Technology of China. For chronic liver injury and fibrosis, male 7 to 10-week-old C57BL/6 and HBV-tg mice (weighing about 20-25 g) were injected (intraperitoneally, i.p., 2 times a week) with 0.5 μL per gram of body weight of pure CCl4 diluted with olive oil (Sigma). After several weeks’ injections (2, 4, 10, and 14 weeks, respectively), mice were sacrificed 72 hours following the last CCl4 injection, and liver tissues and serum were collected. For acute liver injury, both mice were injected CCl4 once and then killed and analyzed at different timepoints.

showing bile acid–dependent liver growth and regeneration18 Seru

showing bile acid–dependent liver growth and regeneration.18 Serum ALT and AST levels were higher in both cholic acid–fed groups, but not different between WT and KO mice (data not shown).

However, serum total bile acid levels in cholic acid–fed KO mice were approximately five-fold higher and hepatic bile acid levels three-fold higher than in WT mice, suggesting defective ability to regulate serum and liver bile acid levels (Fig. 6C,D). Expression of the sinusoidal bile acid uptake transporters Ntcp, Slco1a1, and Slco1b2 were lower in both cholic acid–fed groups (Fig. 7A). Expression of the latter two genes was also lower in chow-fed KO mice. Expression of the basolateral efflux transporters Abcc3 (Mrp3) and Abcc4 (Mrp4) was not different, Wnt inhibitor although there was a trend toward higher 5-Fluoracil in vitro Abcc4 levels in KO mice. Among the canalicular transporters, expression of Bsep (Abcb11) was lower in cholic acid–fed KO mice, whereas Abcb4 (Mdr2) was up-regulated in both cholic acid–fed

groups (Fig. 7B). Expression levels of other sinusoidal transporters were similar between the cholic acid–fed groups. Of the bile acid regulatory genes, expression of farnesoid X receptor (FXR) was lower in both cholic acid–fed groups. However, Shp-1 expression, a downstream target of FXR, was up-regulated in both WT and KO mice on a cholic acid diet (Fig. 7C). Fgf4r levels were similar in all four groups. Expression of constitutive androstane receptor (CAR) was lower in both cholic acid–fed groups and in chow-fed KO mice. However, despite lower expression levels of CAR, KO mice had higher expression of the downstream target of CAR, Cyp2b10. This result suggests that activation of CAR, possibly by a post-transcriptional mechanism, occurs in KO mice and may represent

a Methane monooxygenase protective mechanism to down-regulate bile acid biosynthetic genes. PPARα expression was higher in both cholic acid groups whereas pregnane X receptor expression was lower in cholic acid–fed KO mice. After H&E staining, histology samples from WT mice showed mildly increased lobular inflammation on cholic acid diet (Fig. 8). On the other hand, cholic acid–fed KO mice had increased ductular reaction and greater lobular inflammation on cholic acid diet along with increased pericellular fibrosis on reticulin staining. Staining for F-actin showed that WT mice on cholic acid diet had dilated bile canaliculi, likely reflecting the choleretic effect of bile acids (Fig. 8, bottom panel). However, the interconnected lattice-like structure of canaliculi was preserved in WT livers on cholic acid diet. On the other hand, KO mice on cholic acid diet had canaliculi that were not only dilated but also tortuous and distorted (Fig. 8P). Formation and excretion of bile is one of the important functions of the liver. This task is achieved by the coordinated action of multiple proteins and cellular organelles.

The case presented

illustrates a young patient with acqui

The case presented

illustrates a young patient with acquired FXIII deficiency with a good clinical response to cryoprecipitate and difficulty in hemostasis monitoring utilizing clinically available assays. “
“Many risk factors for falls identified in the general population are found in patients with haemophilia. Furthermore, fall risk increases with age and patients with haemophilia are increasingly entering the over 65 age group. After a fall occurs, there are often Kinase Inhibitor Library mouse behavioural changes that have significant health consequences and further increase fall risk. Fall risk can be quickly assessed in the clinical setting with specific questions in the medical history and by a variety of performance-based screening tools. Identification of fall risk enables early intervention, thereby preventing injury and fear of physical

activity, both of which have been associated with falling and may carry an increased risk in patients with haemophilia. Review of the existing literature on assessment of fall Protein Tyrosine Kinase inhibitor risk reveals the importance of screening in the clinical setting, which is commonly done via a fall history and performance-based assessment tools. Selecting appropriate fall risk screening tools is an important step in identifying and providing optimal interventions for those at risk. Assessments of fall history, fear of falling, gait velocity, gait variability and vestibular dysfunction are suggested as screening tools for patients with haemophilia. Additional research is needed to determine the optimal screening, evaluation and treatment techniques for these patients. The longitudinal physical therapy care provided by Haemophilia Treatment Centres presents a unique opportunity for instituting measures that will reduce the incidence of falling in patients with haemophilia. “
“Factor XIII (FXIII) deficiency is a rare congenital bleeding disorder. There is a paucity of data

in MYO10 the literature about obstetrics and gynaecological problems in women affected by FXIII deficiency. The aim of this study was to examine gynaecological problems and obstetric complications and outcome in women with congenital FXIII deficiency. An electronic search was performed to identify the published literature on PUBMED, MEDLINE, EMBASE, Journals @OVID and CINAHL Plus databases using the following keywords: ‘congenital factor XIII deficiency’ AND ‘women OR Pregnancy’. A total of 39 relevant articles were found and included in this systematic review; 27 case reports and 12 case series dating from 1964 to 2012. A total of 121 women were identified. Menorrhagia (26%) was the second most common bleeding reported after umbilical bleeding. Ovulation bleeding reported in 8% of women. Among 63 women, 192 pregnancies were reported; of these, 127 (66%) resulted in a miscarriage and 65 (34%) reached viability stage. In 136 pregnancies without prophylactic therapy, 124 (91%) resulted in a miscarriage and 12(9%) progressed to viability stage.

In DDC-fed animals, an HF diet resulted in greater liver injury a

In DDC-fed animals, an HF diet resulted in greater liver injury and up-regulation of inflammation-related genes. As a potential mechanism, K8/K18 accumulation and increased ecto-5′-nucleotidase (CD73) levels were noted. In the genetically BAY 57-1293 in vivo susceptible K8tg mice, HF diet triggered hepatocellular injury, ballooning, apoptosis, inflammation, and MDB development by way of 1) decreased expression of the major stress-inducible chaperone Hsp72 with appearance of misfolded keratins; 2) elevated levels of the transglutaminase

2 (TG2); 3) increased K8 phosphorylation at S74 with subsequent TG2-mediated crosslinking of phosphorylated K8; and 4) higher production of the MDB-modifier gene CD73. Conclusion:

Our data demonstrate that HF diet triggers aggregate formation and development of liver injury in susceptible individuals through misfolding and crosslinking of excess K8. (Hepatology 2014;60:169–178) “
“Serum ferritin was recently reported to have low diagnostic accuracy for the detection of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). To corroborate these findings, we investigated the diagnostic accuracy of serum ferritin levels for detecting PD 332991 liver fibrosis in NAFLD patients utilizing a large Japanese cohort database. A total 1201 biopsy-proven NAFLD patients, seen between 2001 and 2013, were enrolled into the Japan Study Group of NAFLD. Analysis

was performed on data from this cohort comparing between serum ferritin levels and hepatic histology. Serum ferritin increased with increasing histological grade of steatosis, lobular inflammation and ballooning. Multivariate analyses revealed that sex differences, steatotic grade and fibrotic stage were independently associated with serum Reverse transcriptase ferritin levels (P < 0.0001, <0.0001, 0.0248, respectively). However, statistical analyses performed using serum ferritin levels demonstrated that the area under the receiver–operator curve for detecting fibrosis was not adequate for rigorous prediction. Several factors including sex differences, steatosis and fibrosis were found to correlate with serum ferritin levels. Therefore, serum ferritin may have low diagnostic accuracy for specifically detecting liver fibrosis in NAFLD patients due to the involvement of multiple hepatocellular processes. Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver injury in many countries around the world.[1] NAFLD represents a spectrum of conditions that are histologically characterized by macrovesicular hepatic steatosis and a diagnosis is made in patients who have not consumed alcohol in amounts sufficient to be considered harmful to the liver.