25 The water-soluble versions of silybin A and silybin B found in Legalon-SIL contain two succinate moieties that increase the molecular weight of the compound by over 244 atomic mass units, from 482 to 726. Thus, the water-soluble molecules are quite different chemically from the natural compounds, which are insoluble in water, and as a result the metabolism and biological effects of the compounds may differ. However,

in our study, silymarin did not inhibit HCV RNA and protein expression in multiple independent replicon cell lines that did not produce infectious progeny viruses, in agreement with a recent study showing that silymarin did not inhibit HCV AZD8055 NS5A protein or RNA expression in a subgenomic replicon cell line.36 The data suggest that blockade of polymerase activity is not a major antiviral mechanism, at least in the HCVcc system. Instead, we provided evidence to suggest that inhibition of virus entry and virus transmission contribute to the antiviral effects of silymarin. Indeed, silymarin blocked the entry of three different enveloped pseudoviruses and also potently inhibited the fusion of liposome membranes. Silymarin flavonolignans belong to the family of phytoestrogens and are composed of a phenylbenzopyrone structure.4 The structures of these molecules are relatively hydrophobic, so it is possible that silymarin may act by incorporating into lipid membranes of both viruses and target cells, or at least

may display partition into lipid bilayers, similar to other plant flavonoids.37 This would signaling pathway lead to the stabilization of membranes by silymarin, which would in turn become less prone to fusion.

This behavior is reminiscent of arbidol, a broad-spectrum antiviral inhibiting HCV entry, membrane fusion, and replication.24 This hypothesis is further corroborated MCE by our observations that silymarin blocks cell entry of pseudotyped particles of other enveloped viruses such as VSVpp and MLVpp. Future studies will focus on further dissecting these mechanisms. We also showed that silymarin inhibits MTP activity, apoB secretion, and production of infectious virus particles. In support of this argument and in agreement with the results obtained in the current report, the flavonoid taxifolin, which is present in silymarin, has been shown to block MTP activity and apoB secretion.38 Silymarin has also been shown to alter lipid profiles,39 so it is possible that the botanical may block virus transmission by targeting multiple components of lipid metabolism. Silymarin does many things to cells, including modulation of signal transduction,40 the redox state,41 T-cell function,6, 31 and nuclear factor kappa B.42 These studies suggest that direct effects of silymarin on cell functions are responsible for the prevention of liver disease in many animal models.33-35 We therefore hypothesize that silymarin’s blockade of virus entry and transmission occurs by targeting the host cell.

026) in patients with advanced fibrosis. In multivariate analysis, lower adiponectin was independently associated with NASH (odds ratio = 7.7, 95% confidence interval = 1.5–39.9, P = 0.014, for the subgroup with adiponectin below the median value), whereas both

lower adiponectin and lower TGF-β1 levels were associated with PD-0332991 datasheet advanced fibrosis. Low adiponectin and low TGF-β1 are associated with severest NAFLD stages in T2DM and may be a valuable tool to support liver biopsy indication in this setting. “
“Ursodeoxycholic acid, which in vivo is converted to its taurine conjugate tauroursodeoxycholic acid (TUDC), is a mainstay for the treatment of cholestatic liver disease. Earlier work showed that TUDC exerts its choleretic properties in the perfused rat liver in an α5β1 integrin-mediated

way. However, the molecular basis of TUDC-sensing in the liver is unknown. We herein show that TUDC (20 μmol/L) induces in perfused rat liver and human HepG2 cells the rapid appearance of the active conformation of the β1 subunit of α5β1 integrins, followed by an activating phosphorylation of extracellular signal-regulated kinases. TUDC-induced kinase activation was no longer observed after β1 integrin knockdown in isolated rat hepatocytes or in the presence of an integrin-antagonistic NVP-BKM120 manufacturer hexapeptide in perfused rat liver. TUDC-induced β1 integrin activation MCE公司 occurred predominantly inside the hepatocyte and required TUDC uptake by way of the Na+/taurocholate cotransporting peptide. Molecular dynamics simulations of a 3D model of α5β1 integrin with TUDC bound revealed significant conformational changes within the head region that have been

linked to integrin activation before. Conclusions: TUDC can directly activate intrahepatocytic β1 integrins, which trigger signal transduction pathways toward choleresis. (HEPATOLOGY 2013) Ursodesoxycholic acid, which is rapidly conjugated with taurine in vivo,1 is widely used for the treatment of cholestatic liver disease.2-4 Its beneficial effect is thought to involve a stimulation of hepatocellular bile secretion5, 6 as well as cytoprotective and antiapoptotic effects.7-10 The choleretic action of tauroursodeoxycholic acid (TUDC) is largely due to a rapid insertion of intracellularly stored transport ATPases into the canalicular membrane, such as the bile salt export pump (Bsep) and multidrug resistance protein-2 (Mrp2).11 However, the molecular basis of TUDC-sensing is still unknown. Evidence has been presented that the TUDC-induced insertion of Bsep into the canalicular membrane involves an activation of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3 kinase), and c-Src, which trigger downstream a dual activation of extracellular signal-regulated kinases (Erks) and p38 mitogen-activated protein kinase (p38MAPK).

026) in patients with advanced fibrosis. In multivariate analysis, lower adiponectin was independently associated with NASH (odds ratio = 7.7, 95% confidence interval = 1.5–39.9, P = 0.014, for the subgroup with adiponectin below the median value), whereas both

lower adiponectin and lower TGF-β1 levels were associated with learn more advanced fibrosis. Low adiponectin and low TGF-β1 are associated with severest NAFLD stages in T2DM and may be a valuable tool to support liver biopsy indication in this setting. “
“Ursodeoxycholic acid, which in vivo is converted to its taurine conjugate tauroursodeoxycholic acid (TUDC), is a mainstay for the treatment of cholestatic liver disease. Earlier work showed that TUDC exerts its choleretic properties in the perfused rat liver in an α5β1 integrin-mediated

way. However, the molecular basis of TUDC-sensing in the liver is unknown. We herein show that TUDC (20 μmol/L) induces in perfused rat liver and human HepG2 cells the rapid appearance of the active conformation of the β1 subunit of α5β1 integrins, followed by an activating phosphorylation of extracellular signal-regulated kinases. TUDC-induced kinase activation was no longer observed after β1 integrin knockdown in isolated rat hepatocytes or in the presence of an integrin-antagonistic selleck kinase inhibitor hexapeptide in perfused rat liver. TUDC-induced β1 integrin activation MCE公司 occurred predominantly inside the hepatocyte and required TUDC uptake by way of the Na+/taurocholate cotransporting peptide. Molecular dynamics simulations of a 3D model of α5β1 integrin with TUDC bound revealed significant conformational changes within the head region that have been

linked to integrin activation before. Conclusions: TUDC can directly activate intrahepatocytic β1 integrins, which trigger signal transduction pathways toward choleresis. (HEPATOLOGY 2013) Ursodesoxycholic acid, which is rapidly conjugated with taurine in vivo,1 is widely used for the treatment of cholestatic liver disease.2-4 Its beneficial effect is thought to involve a stimulation of hepatocellular bile secretion5, 6 as well as cytoprotective and antiapoptotic effects.7-10 The choleretic action of tauroursodeoxycholic acid (TUDC) is largely due to a rapid insertion of intracellularly stored transport ATPases into the canalicular membrane, such as the bile salt export pump (Bsep) and multidrug resistance protein-2 (Mrp2).11 However, the molecular basis of TUDC-sensing is still unknown. Evidence has been presented that the TUDC-induced insertion of Bsep into the canalicular membrane involves an activation of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3 kinase), and c-Src, which trigger downstream a dual activation of extracellular signal-regulated kinases (Erks) and p38 mitogen-activated protein kinase (p38MAPK).

“
“Purpose: The effect of dental fabrication procedures

of zirconia monolithic restorations and changes in properties during low-temperature exposure in the oral environment is not completely understood. The purpose of this study was to investigate the effect of procedures for fabrication of dental restorations by low-temperature simulation and relative changes of flexural strength, Navitoclax supplier nanoindentation hardness, Young’s modulus, surface roughness, and structural stability of yttria-stabilized zirconia. Materials and Methods: A total of 64 zirconia specimens were prepared to simulate dental practice. The specimens were divided into the control group and the accelerated aging group. The simulated group followed the same procedure as the control group except for the aging treatment. Atomic force microscopy RG-7388 mw was used to measure surface roughness. The degree of tetragonal-to-monoclinic transformation was determined using X-ray diffraction. Nanoindentation

hardness and modulus measurements were carried out on the surface of the zirconia specimens using a nanoindenter XP/G200 system. The yttria levels for nonaged and aged specimens were measured using energy dispersive spectroscopy. Flexural strength was determined using the piston-on-three-ball test. The t-test was used to determine statistical significance. Results: Means and standard deviations were calculated using all observations for each condition and evaluated using a group t-test (p < 0.05). The LTD treatment resulted in increased surface roughness (from 12.23

nm to 21.56 nm for Ra and 15.06 nm to 27.45 nm for RMS) and monoclinic phase fractions (from 2% to 21%), with a concomitant decrease in hardness (from 16.56 GPa to 15.14 GPa) and modulus (from 275.68 GPa to 256.56 GPa). Yttria content (from 4.43% to 4.46%) and flexural strength (from 586 MPa to 578 MPa) were not significantly altered, supporting longer term in vivo function without biomechanical fracture. Conclusion: The LTD treatment induced the tetragonal-to-monoclinic transformation with surface roughening in zirconia prepared using dental procedures. “
“Purpose: Carbon nanotubes are used in dentistry, although there are no adequate scientific data to support their use in acrylic resins. The polymerization MCE公司 shrinkage that occurs with polymethylmethacrylate (PMMA) resins is well known. This study compared the polymerization shrinkage of denture base acrylic resin with and without micro-additions of carbon nanotubes. Materials and Methods: Two materials were used, PMMA resin and multiwalled carbon nanotubes. Four groups were established of 10 specimens each according to the weight percent of carbon nanotubes dispersed and disintegrated in the monomer: group I (0.5% of carbon nanotubes in monomer), II (0.25%), III (0.125%), and IV (control group, 0%).

As a result, the efficacy of these agents in the treatment of gastroparesis is limited. Another option is surgical therapy of gastroparesis.14–16 Complete gastrectomy has been mainly employed to improve the symptoms in postsurgical gastroparesis (PSG).17,18 Therefore, gastroparesis brings continuing challenges

for PLX-4720 price physicians. In recent years, high-frequency gastric electrical stimulation (GES) has emerged as a new therapeutic modality for patients with refractory gastroparesis.19–22 High-frequency GES with the Enterra Therapy system (Medtronic, Minneapolis, MN, USA) has been approved for use under the Humanitarian Device Exemption by the US Food and Drug Administration for the treatment of Angiogenesis inhibitor gastroparesis of diabetic and idiopathic etiologies that are refractory to all medical management.23 The device produces intermittent bursts of high-frequency (∼14 cycles per second), short-duration pulses (∼330 µs) that are three to four times faster than the native gastric slow wave frequency. Recent studies have shown that high-frequency GES improves nausea and vomiting scores, health-related quality of life, hemoglobin A1C (HbA1c), and health-care costs.24–28 However, the effects on gastric emptying are not

uniform. The sample size of most treatment trials and clinical experiences are relatively small, although results are generally positive.29–53 Therefore, larger patient sample sizes would be preferred in order to obtain

a reliable result. Although O’Grady et al. indicated that this kind of GES, which is neurostimulation, can improve symptoms and gastric emptying,54 the sample size in the meta-analysis was small, and data in abstracts were also included, which might decrease the accuracy of the study. However, Zhang and Chen doubted that high-frequency GES improved MCE gastric emptying and could explain the improvement of symptoms.55 As a result, the relationship between the improvement of symptoms and gastric emptying is still a debated issue needing further research. It should also be noted that neither O’Grady et al. nor Zhang and Chen evaluated a detailed subgroup analysis of the main etiologies of gastroparesis patients, namely diabetes mellitus, idiopathic, and previous surgical procedures.56 Therefore, we are faced with discussion about whether the improvement of gastric emptying is associated with symptom improvement, and whether high-frequency GES has the same effect on the diabetic gastroparesis (DG), idiopathic gastroparesis (IG), and PSG subgroups. In order to address these problems, the primary purpose of this meta-analysis was to acquire more data about gastroparesis patients treated by high-frequency GES, while also taking into consideration that the quality of papers in the analysis would vary.

22 It is thus necessary to further investigate the effect of Pol on these pathways so as to obtain a more accurate picture. Two reports showed that HBV suppresses IFN-α signaling by inhibiting Ferroptosis cancer STAT1 methylation,23, 24 however, the potential role for STAT1 methylation remains controversial.25,

26 Since the Pol-targeted importin-α5 is important in nuclear import of certain molecules and PKC-δ plays a fundamental role in growth regulation by targeting specific substrates27 and was recently reported to be involved in the IFN-α–mediated suppression of HBV enhancer II activation,28 it is also important to consider the possibility that Pol may cause disturbances in these processes. By ectopic expression and knockdown experiments, we determined that Pol is responsible for the HBV-mediated inhibition of IFN-α signaling. In contrast to HBV structural proteins like B-Raf inhibitor drug core and HBs, Pol is believed to be produced at a much lower level during viral replication. A recent paper showed that polyinosinic:polycytidylic acid-induced IFN-α/β-dependent STAT3 phosphorylation was inhibited when the viral load was high.29 As our data showed that Pol inhibits polyinosinic:polycytidylic acid-induced IFN production8 and IFN-α–induced serine phosphorylation of STAT3 in a dose-dependent manner (Fig. 3D), we hypothesize that the physiological levels of Pol are correlated with the

viral load and that HBV can only efficiently inhibit the medchemexpress IFN system when the viral replication level is high. This scenario is also supported by the clinical observation that

patients with high HBV DNA levels are mostly nonresponders to IFN-α therapy.2, 3 In addition, TP and RH domains were found to exhibit similar inhibitory effects compared with full-length Pol (Fig. 6). Several studies have demonstrated the in vivo expression of viral proteins encoded by HBV spliced RNAs, which contain domains derived from the open reading frame of the Pol gene.30 The function of these proteins remains obscure. It is thus to consider the hypothesis that such splice variants may represent a source of the proteins containing TP or RH domains and contribute to the suppression of the host antiviral responses. We used a hydrodynamic-based mouse model to substantiate the in vitro findings. Intriguingly, the basal levels of Mx1 were significantly higher in HBV-transfected livers compared with those in control mice, and ISG induction was strongly inhibited by HBV in the mouse liver (Fig. 7A). Although these results appear contrary to previous reports indicating that HBV is a “stealth” virus early in the infection31 and the findings obtained in vitro that HBV inhibits ISGs expression in hepatic cells by only two- to four-fold (Supporting Fig. 1), they are similar to the findings obtained in HBV-infected chimeric mice.

Hofmann, Axel Baumgarten, Ralph Link, Peter R. Geyer, Hanns-Friedrich F. Loehr, Andreas Schober, Gero Moog, Stefanie Holm, Renate Heyne Introduction: A simple non invasive score (Fibrofast) was developed using five routine laboratory tests (ALT, AST, Alkaline phosphatase, Albumin and Platelets count) for the detection of significant hepatic fibrosis in patients with chronic hepatitis C (CHC) (Attallah et al., Hepatology Research (2006) 34: 163-169). Accordingly, we validated the accuracy of Fibrofast score on 1067 cases from several

international centers, which revealed a sensitivity of 61.5 %, specificity of 81.1%, positive predictive value of 59% and negative predictive value of 82.6%. This indicated that Alectinib the performance of the test is not enough as a suggestive alternative to liver biopsy. The aim of this study was to develop a new cut off score of the test that allows the diagnosis of established cirrhosis (F4) and (F0-F3) ensuring accuracy (more MI-503 than 95%). Method: Subjects were

1 873 patients with CHC. All biopsies were scored using METAVIR system. Our fibrosis score (Fibrofast) were measured and the performance of the new cut off score were done using ROC curve. Results: Liver biopsy showed that 1646 cases (F0F3) and 227 cases established cirrhosis (F4). Using the ROC curve we develop new 2 cut off scores. The positive one is for

diagnosis of (F0-F3) and the negative one is for diagnosis of established cirrhosis (F4).145 out of 227 cases (63.87%) were established cirrhosis and 328 out of 1646 cases (19.9%) (F0F3) i. e.463 out 1873 cases (24.7%) was positively correlated with liver biopsy (r = 0.393, P= 0.0〇1), sensitivity 95%, specificity 95%. Conclusion: Fibrofast score with the new two cut off scores could be an alternative MCE to liver biopsy in about onefourth of the patients with sensitivity 95% and specificity 95%. Being non invasive, it could be an ideal marker for follow up during and after treatment in many patients. Disclosures: The following people have nothing to disclose: Gamal Shiha, Waleed Samir, Khaled T. Zalata, Amira Elbeeh, Ammal Metwally (Background and Aim) Interferon response is an important component for the virus elimination even in the DAA-based interferon-free regimen. We established stable culture system of chimeric viruses between HCV-TMD1(G-2b) and JFH1 (G-2a).

13 Superoxide dismutase (SOD) activity in liver homogenate was determined according to the method described by Nandi and Chatterjee.14 This method is based on the ability of SOD to inhibit the auto-oxidation of pyrogallol at an alkaline pH. One unit of SOD is described as the amount of enzyme required to cause 50% inhibition of pyrogallol auto-oxidation. The glutathione (GSH) content

in the liver homogenate was determined using the method of Van Dooran et al.15 The basis of the GSH determination method is the reaction of Ellman’s reagent (5,5′-dithiobis-[2-nitrobenzoic acid]) with thiol groups of GSH at pH 8.0 to produce the yellow 5-thiol-2-nitrobenzoate anion. Glutathione S-transferase (GST) activity was determined according to the method of Habig et al.16 In this assay, GST catalyzes the conjugation of GSH with 1-chloro-2,4-dinitrobenzene, producing Dorsomorphin molecular weight a chromophore at 340 nm. The total protein contents of liver tissues were determined according to the Lowry method as modified by Peterson.17 Absorbances were recorded using a Shimadzu recording

spectrophotometer (UV-160) in all measurements. Liver cancer cell MI-503 manufacturer line HepG2 were maintained in Roswell Park Memorial Institute-160 medium with 10% fetal bovine serum and 1% of 100 U/mL penicillin and 100 μg/mL streptomycin at 37°C inside a humidified incubator with 5% CO2 and 95% room air. Cells were subcultured every 4-7 days with trypsin/ethylenediamine tetraacetic acid (1:250; PAA Laboratory, Germany). Cells were treated with several concentrations of saffron extract for several time points. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole) proliferation assay was used in the HepG2 cell line to assess the effect on cell proliferation of a range of concentrations of saffron extract.

Cells (104) were plated and grown in 200 μL of growth medium in 96-well microtiter plates. After an overnight attachment period, cells were treated with varying concentrations of saffron extract (1.0, 2.0, 4.0, and 6.0 mg/mL) prepared from a 100 上海皓元医药股份有限公司 mg/mL stock solution dissolved in water. All studies were performed in triplicate and repeated three times independently. Cell growth was quantified by the ability of living cells to reduce the yellow dye MTT to a purple formazan product. Cells were incubated with MTT (Sigma) at 37°C in a humidified 5% CO2 atmosphere for 2 hours. The MTT formazan product was then dissolved in dimethylsulfoxide, and absorbance was measured at 570 nm in a microplate reader. One day before treatment, cells were seeded at a density of 1.2 × 106 cells per plate. After the indicated times, the cells were harvested by trypsin release, washed twice with phosphate-buffered saline, fixed with 70% ethanol, treated with 1% ribonuclease, and finally stained with propidium iodide (100 μg/mL final concentration).

9 However, activities of NOX1 as well as NOX2 can be regulated by p47phox in some cell types.31 Studies in vascular smooth muscle cells from normal and p47phox-deficient mice suggest that p47phox participates in an oxidative response that involves NOX1 as the core catalytic oxidase Fer-1 supplier component in these cells.32, 33 Moreover, coexpression of NOX1 with NOXO1 and NOXA1 leads to stimulus-independent, high-level superoxide generation,

whereas stimulus dependence of NOX1 was restored when p47phox was used to replace its homologue NOXO1.11 Thus, p47phox appears to involve a functional partnership with both NOX2 and NOX1 in the liver, resulting in hepatic ROS generation and fibrosis. Compared with WT mice, NOX1KO and NOX2KO mice showed weak hepatic fibrosis after both CCl4 and BDL treatments. However, low serum ALT levels were only observed in CCl4-treated NOX1KO and NOX2KO mice, but not in those www.selleckchem.com/products/pci-32765.html treated with BDL. NOX1KO and NOX2KO mice showed low hepatic lipid peroxidation after both CCl4 and BDL treatments. Similar to liver injury, lipid

peroxidation in NOX1KO and NOX2KO mice was more evidently reduced after CCl4 treatment than after BDL treatment. We found strong up-regulation of NOX2 and its regulators such as p40phox, p47phox, p67phox in in vivo–activated HSCs by CCl4 compared with quiescent HSCs, suggesting a stronger participation of NOX in CCl4-induced liver fibrosis. Hydrophobic bile acids that accumulate during cholestasis stimulate the generation of ROS in hepatocyte mitochondria through induction of mitochondrial membrane transition.34 NOX-independent ROS such as mitochondria-produced ROS might play a more important role in the generation of hepatic lipid peroxidation in BDL than in CCl4.

Our current study characterizes the functional contribution of different NOX1- and NOX2-expressing cell populations to hepatic fibrosis. Through experiments using NOX1 and NOX2 BM chimeric 上海皓元医药股份有限公司 mice, we demonstrate that NOX1 mediates fibrogenic effects in endogenous liver cells, and NOX2 mediates fibrogenic effects in both endogenous liver cells and BM-derived cells. In this study, NOX2 BM chimeric mice that expressed NOX2 in endogenous liver cells but not BM-derived cells (NOX2KO BMWT) showed a modest but significant reduction of fibrosis compared with WT mice. These results are consistent with our previous study using p47phox BM chimeric mice. p47phox BM chimeric mice that expressed p47phox in endogenous liver cells but not BM-derived cells (p47phoxKO BMWT) showed an ≈25% reduction in fibrosis, whereas chimeric mice with WT BM-derived cells and p47phoxKO endogenous liver cells (WT BMp47phoxKO) showed an ≈60% reduction in fibrosis.26 Taken together, NOX2 in both endogenous liver cells and BM-derived cells contributes to liver fibrosis, with the endogenous liver cells making the greater contribution.

Satapathy

– Advisory Committees or Review Panels: Gilead The following people have nothing to disclose: Cheri Ogwo, Jason M. Vanatta, James Eason Background-Aims:Data on Sexual find more Dysfunction(SD) in cirrhotic patients are limited.Sexual function is a complex area of human behavior with great impact on Quality-of-Life.Despite its relevance,it is rarely evaluated in clinical practice in cirrhotic patients.Our aim was to evaluate in detail the sexual function of patients with end-stage liver disease in the waiting list for LT and to compare it with the results after LT and with that of a controlled group from the general population matched by age and gender.Methods:Changes in Sexual Functioning Questionnaire Selleckchem Pexidartinib were used to evaluate SD in cirrhotic patients awaiting LT and in the post-LT setting 1 year after

transplant.Clinical data as well as a complete set of sexual hormonal profile were obtained in the same periods.Controls were given the same questionnaires.Results:58 patients,69% men with a median MELD 19,were included and compared to 58 controls.92% of men presented SD during the waiting period for LT compared to 63% of controls(p<0.01).In women, of whom 88% were in menopausal stage, SD was present in 94% compared to 72% of controls(p=0.7).One year post-LT,SD decreased to 74% in men(p=0.09),while no changes were detected in women.In men,sex hormones showed a pattern of central hypogonad-ism

during the pretransplant period with a MCE公司 decrease in male sex hormones(free testosterone in 83%,testosterone 53%)and normal values of FSH and LH(in 72% and 81% of men).In addition,an increase of estradiol and prolactin in 86% and 72 %,respectively,were observed.Levels of DHEA-Sulphate,an androgen produced in the adrenal gland,were decreased in 97% of men. Sex hormones results one year after LT showed FSH and LH values above the normal range, a significant increase with respect to the pre-transplantation period(p=0.07 and 0.005,respectively);a descrease of prolactin to normal levels (p=0.2),and estrogen levels, while still slightly above the normal range, had decreased(p=0.2). There was an increase in testosterone and free testosterone levels(P=0.05 and 0,2). Levels of DHEA-Sulphate remained low after transplantation. Conclusion:SD,an infra-estimated condition,is extremely common in cirrhotic patients awaiting LT.Besides central hypogo-nadism,the reduced levels of DHEA,possibly due to adrenal dysfunction,is an aspect that deserves further investigation:-sexual dysfunction could,in part,be another manifestation of the recently coined“hepatoadrenal syndrome”.LT improves SD in men,demonstrated both subjectively (questionnaires) and objectively,with a normalization in sex hormone levels in most cases and the disappearance of central hypogonadism with a compensatory increase of pituitary hormones synthesis(FSH and LH).