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Unlabelled: The principal limitations of the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. Methods: A modified Delphi process was led by three large pan-national liver associations. Consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. Results: A total of 236 panellists from 56 countries participated in four online surveys and two hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83% and 78%, respectively. 74% of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms 'non-alcoholic' and 'fatty' were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease (SLD) was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least one of five cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic SLD. A new category, outside pure MASLD, termed MetALD was selected to describe those with MASLD who consume greater amounts of alcohol per week (140 to 350g/week and 210 to 420g/week for females and males respectively). Conclusions: The new nomenclature and diagnostic criteria are widely supported, non-stigmatising and can improve awareness and patient identification.

The presented text deals with research into the influence of the printing layers’ orientation on crack propagation in an AlSi10Mg material specimen, produced by additive technology, using the Direct Metal Laser Sintering (DMLS) method. It is a method based on sintering and melting layers of powder material using a laser beam. The material specimen is presented as a Compact Tension test specimen and is printed in four different defined orientations (topology) of the printing layers—0°, 45°, 90°, and twice 90°. The normalized specimen is loaded cyclically, where the crack length is measured and recorded, and at the same time, the crack growth rate is determined. The evaluation of the experiment shows an apparent influence of the topology, which is essential especially for possible use in the design and technical preparation of the production of real machine parts in industrial practice. Simultaneously with the measurement results, other influencing factors are listed, especially product postprocessing and the measurement method used. The hypothesis of crack propagation using Computer Aided Engineering/Finite Element Method (CAE/FEM) simulation is also stated here based on the achieved results.

3D printing is one of the most progressive additive technologies today. It finds its application also in industry. In terms of mechanical properties, the printing design of the product is an important parameter. The presented study investigates the effects of the printing design of a thin-walled 3D polymer model on the mechanical properties of the model. The material used for printing was acrylonitrile-butadiene-styrene (ABS) and the 3D print method was Fused Deposition Modeling (FDM). ABS was tested at various die temperatures and with various printing designs at a constant 3D print speed and identical print bed temperature. We examined the effect of printing temperature and product printing design on the resulting mechanical properties. We compared theoretical and experimental results by CAE–FEM Advanced Simulation modules. Results tensile deformations at maximum load by experiment and simulations are comparable. The best results of testing the mechanical properties were found in the pattern printed at a 45° angle at temperature 285 °C.

Additive technologies are a dynamically evolving category of manufacturing methods for a wide range of industries, particularly engineering and related fields. Compared to traditional technologies based on chip machining, molding and casting, they offer new production options, particularly for complex shape components. At the same time, however, there are differences and limits that must be taken into account when designing functional machine parts. The important quality parameters of the products are in particular the dimensions and the quality of the surface. These factors are of fundamental importance for the subsequent assembly and function of a component in a plant assembly. They determine, together with the structural material properties, the usability of the component and the economic efficiency of the production in order to achieve the finished product with the minimum need for postprocessing the finished part. The submited text presents the results of the quality parameter research carried out on 3D print products made by the DMLS method, where the focus is put on the assessment of linear dimensions and the surface quality of samples from three selected materials and a combination of two print modifications. The measurement results are compared to generally valid standards and tabulated values to verify and eventually modify table values for use when designing a design solution with the use of 3D print products.

This article analyzes the integrated effect of industrial by-products (spent uidized bed catalytic cracking catalyst waste (FCCCw) and paper sludge waste (PSw) generated in paper manufacturing) combined with nano-SiO2 (NS) on the properties of cement binder, when a certain part of the binder is replaced with the said by-products in the cement mix. Standard testing methods were used to analyze the physical and mechanical properties of cement-based materials. For structure analysis, we used X-ray diffraction (XRD), derivative thermogravimetry (DTG), mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). It was found that the replacement of cement by a combined additive of FCCCw, PSw and NS is important not only for ecological reasons (abatement of CO2 emissions and recovery of waste through secondary raw materials), but also in order to enhance the properties of cement-based binders. Presumably, higher amounts of calcium silicate hydrate (CSH) and calcium alumina silicate hydrate (CASH) in the compound binder are the result of the low content of portlandite and alite in the test specimens. The specimens modied with all three additives had the highest density (~2100 kg/m3), ultrasonic pulse velocity (UPV) (~4160 m/s) and compressive strength (~105 MPa), which was ~40% higher than in the control specimens. The average pore diameter of the complex binder decreased by 21%, whereas the median pore diameter decreased by 47%. Tento článek analyzuje integrovaný účinek průmyslových vedlejších produktů (vyhořelého lože odpad katalyzátoru z katalytického krakování (FCCCw) a odpad z papírového kalu (PSw) vznikající při výrobě papíru) v kombinaci s nano-SiO2 (NS) o vlastnostech cementového pojiva, když je určitá část pojiva nahrazena uvedenými vedlejšími produkty v cementová směs. K analýze fyzikálních a mechanických vlastností materiálů na bázi cementu byly použity standardní zkušební metody. Pro strukturní analýzu jsme použili rentgenovou difrakci (XRD), derivační termogravimetrii (DTG), rtuťovou vnikovou porozimetrii (MIP) a rastrovací elektronovou mikroskopii (SEM). Bylo zjištěno, že nahrazení cementu kombinovanou přísadou FCCCw, PSw a NS je důležité nejen z ekologických důvodů (snížení emisí CO2 a využití odpadu prostřednictvím druhotných surovin), ale také za účelem zlepšení vlastností cementu - pojiva na bázi. Pravděpodobně vyšší množství hydrátu křemičitanu vápenatého (CSH) a hydrátu křemičitanu vápenato-hlinitého (CASH) ve složeném pojivu jsou výsledkem nízkého obsahu portlanditu a alitu ve zkušebních vzorcích. Vzorky modifikované všemi třemi přísadami měly nejvyšší hustotu (~ 2100 kg / m3), rychlost ultrazvukového pulzu (UPV) (~ 4 160 m / s) a pevnost v tlaku (~ 105 MPa), která byla o ~ 40% vyšší než u kontrolních vzorků. Průměrný průměr pórů komplexního pojiva se snížil o 21%, zatímco střední průměr pórů se snížil o 47%.

Rigid polyurethane (PUR) foam, which has an extensive range of construction, engineering, and healthcare applications, is commonly used in technical practice. PUR foam is a brittle material, and its mechanical material properties are strongly dependent on temperature and strain rate. Our work aimed to create a robust FE model enabling the simulation of PUR foam machining and verify the results of FE simulations using the experiments’ results. We created a complex FE model using the Arbitrary Lagrangian–Eulerian (ALE) method. In the developed FE model, a constitutive material model was used in which the dependence of the strain rate, damage initiation, damage propagation, and plastic deformation on temperature was implemented. To verify the FE analyses’ results with experimentally measured data, we measured the maximum temperature during PUR foam drilling with different densities (10, 25, and 40 PCF) and at various cutting speeds. The FE models with a constant cutting speed of 500 mm/s and various PUR foam densities led to slightly higher Tmax values, where the differences were 13.1% (10 PCF), 7.0% (25 PCF), and 10.0% (40 PCF). The same situation was observed for the simulation results related to various cutting speeds at a constant PUR foam density of 40 PCF, where the differences were 25.3% (133 mm/s), 10.1% (500 mm/s), and 15.5% (833 mm/s). The presented results show that the ALE method provides a good match with the experimental data and can be used for accurate simulation of rigid PUR foam machining.

The replacement of primary raw materials in cement production is a current topic. Potentially usable raw materials include recycled glass. The disadvantage of glass is its tendency to aggregate. The conventional method for the production of blended cement is separate grinding and then homogenizing the components. However, in this case aggregated fine glass in the cement composites acts only physically and mechanically as a filler rather than as an active pozzolan. An interesting option to prevent the formation of aggregates formed from glass is co-grinding. This procedure is not very common in practice. Various ingredients of blended cements have widely different grindabilities, and it is therefore better to grind them separately. The aim is to compare the co-grinding and separate grinding of a combination of Portland clinker and recycled glass. The grindability was tested on clinker, glass, and blended cements prepared by co-grinding and by separate grinding. The results of the experiment show that by co-grinding the components of blended cement with the addition of 20 % of recycled glass as a pozzolan, a synergy effect caused by the various mechanical properties of the components occurs. The aggregation of grains is less significant than during separate grinding and it leads to a better grinding effect. This knowledge can by utilized in the design and processing of new blended cements. Also, co-milling the glass-cement system can eliminate the stage of homogenization, and, therefore save energy.

BACKGROUND/AIMS:Signaling of Gs protein-coupled receptors (GsPCRs) is accomplished by stimulation of adenylyl cyclase, causing an increase of the intracellular cAMP concentration, activation of the intracellular cAMP effectors protein kinase A (PKA) and Epac, and an efflux of cAMP, the function of which is still unclear.METHODS:Activation of adenylyl cyclase by GsPCR agonists or cholera toxin was monitored by measurement of the intracellular cAMP concentration by ELISA, anti-phospho-PKA substrate motif phosphorylation by immunoblotting, and an Epac-FRET assay in the presence and absence of adenosine receptor antagonists or ecto-nucleotide phosphodiesterase/pyrophosphatase2 (eNPP2) inhibitors. The production of AMP from cAMP by recombinant eNPP2 was measured by HPLC. Extracellular adenosine was determined by LC-MS/MS, extracellular ATP by luciferase and LC-MS/MS. The expression of eNPP isoenzymes 1-3 was examined by RT-PCR. The expression of multidrug resistance protein 4 was suppressed by siRNA.RESULTS:Here we show that the activation of GsPCRs and the GsPCRs-independent activation of Gs proteins and adenylyl cyclase by cholera toxin induce stimulation of cell surface adenosine receptors (A2A or A2B adenosine receptors). In PC12 cells stimulation of adenylyl cyclase by GsPCR or cholera toxin caused activation of A2A adenosine receptors by an autocrine signaling pathway involving cAMP efflux through multidrug resistance protein 4 and hydrolysis of released cAMP to AMP by eNPP2. In contrast, in PC3 cells cholera toxin- and GsPCR-induced stimulation of adenylyl cyclase resulted in the activation of A2B adenosine receptors.CONCLUSION:Our findings show that stimulation of adenylyl cyclase causes a remarkable activation of cell surface adenosine receptors. Fil: Pleli, Thomas. Goethe Universitat Frankfurt; Alemania Fil: Mondorf, Antonia. Goethe Universitat Frankfurt; Alemania Fil: Ferreiros, Nerea. Goethe Universitat Frankfurt; Alemania Fil: Thomas, Dominique. Goethe Universitat Frankfurt; Alemania Fil: Dvorak, Karel. Goethe Universitat Frankfurt; Alemania Fil: Biondi, Ricardo Miguel. Goethe Universitat Frankfurt; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Heringdorf, Dagmar Meyer zu. Goethe Universitat Frankfurt; Alemania Fil: Zeuzem, Stefan. Goethe Universitat Frankfurt; Alemania Fil: Geisslinger, Gerd. Goethe Universitat Frankfurt; Alemania Fil: Zimmermann, Herbert. Goethe Universitat Frankfurt; Alemania Fil: Waidmann, Oliver. Goethe Universitat Frankfurt; Alemania Fil: Piiper, Albrecht. Goethe Universitat Frankfurt; Alemania

Recently, ceramic–metallic composite materials (CerMets) have been investigated for orthopaedic applications with promising results. This first generation of bio-CerMets combine the bioactivity of hydroxyapatite with the mechanical stability of titanium to fabricate bioactive, tough and biomechanically more biocompatible osteosynthetic devices. Nonetheless, these first CerMets are not biodegradable materials and a second surgery is required to remove the implant after bone healing. The present work aims to develop the next generation bio-CerMets, which are potential biodegradable materials. The process to produce the new biodegradable CerMet consisted of mixing powder of soluble and osteoconductive alpha tricalcium phosphate with biocompatible and biodegradable iron with consolidation through spark plasma sintering (SPS). The microstructure, composition and mechanical strength of the new CerMet were studied by metallography, x-ray diffraction and diametral tensile strength tests, respectively. The results show that SPS produces CerMet with higher mechanical performance (120 MPa) than the ceramic component alone (29 MPa) and similar mechanical strength to the pure metallic component (129 MPa). Nonetheless, although a short sintering time (10 min) was used, partial transformation of the alpha tricalcium phosphate into its allotropic and slightly less soluble beta phase was observed. Cell adhesion tests show that osteoblasts are able to attach to the CerMet surface, presenting spread morphology regardless of the component of the material with which they are in contact. However, the degradation process restricted to the small volume of the cell culture well quickly reduces the osteoblast viability.

Aims. Nonalcoholic fatty liver disease (NAFLD) is associated with components of the metabolic syndrome (MS) but the prevalence of NAFLD in the Czech Republic is unknown. The aim of this study was to assess the latter in patients with type 2 diabetes (DM2) and to compare the noninvasive fibrosis scores with ultrasound findings in those patients. Methods. 180 consecutive patients with DM2 (mean age 64.2±9.3 years, 63% men) were examined for liver biochemistry, MS parameters and had liver ultrasound. MS was diagnosed according to the International Diabetes Federation. The diagnosis of NAFLD was based on liver ultrasound. Other aetiology of liver lesion was ruled out. Additionally, AST/ALT ratio, APRI, NAFLD fibrosis score, FIB4 and BARD scores were calculated. Results. 93% of patients met the MS criteria, 79% had NAFLD and 13% had ultrasound signs of fibrosis/cirrhosis. NAFLD patients had greater weight (96.9±19.3 vs 84.7±14.7 kg; P=0.003), BMI (32.6±5.2 vs 29.4±5.4 kg/m 2 ; P=0.007), waist circumference (113.8±12.8 vs 107.1±10.3 cm; P=0.033), ALT (0.73±0.57 vs 0.55±0.53 μkat/L, P=0.007) and triglyceridaemia (1.9±1.4 vs 1.4±1 mmol/L; P=0.005) than patients without NAFLD. There were no significant differences in age, sex, cholesterol, fasting glycaemia or glycated haemoglobin. Of calculated scores only the NAFLD fibrosis score revealed significant differences between patients with and without ultrasound signs of fibrosis/cirrhosis (1.027±2.228 vs -0.118±1.402, P=0.026). Conclusion. Patients with DM2 had in the majority of cases NAFLD which was related to weight, BMI, waist circumference and serum triglycerides. The validity of the liver fibrosis scoring system has to be assessed in those patients in the future.

3D printing by the FDM method represents a progressive parts manufacturing technology using available cheap 3D printers. Basic method consists in depositing fibers from the molten plastic material in layers. Common material of the blank is based on polymers. Starting geometry is a 3D digital model of a component created in CAD or obtained by reverse engineering. FDM 3D printing method has certain technological limits, depending on the parameters and configuration of the printing device. Printing of complex parts with the dimensional accuracy and shape demand often requires modification of the model representing correction of related areas. Tools for postprocessing model usually take account of technological settings, eg. plastic coating nozzle parameters, which may particularly for small parts lead to inadequate or unexpected results. The solution may be targeted direct model adjustment. Correction can be performed by design, direct, parametric and non-parametric methods to the 3D model.

One of the possibilities how to increase the efficiency of the deployment of tools for design, simulation and preparing of manufacturing technology is linking engineering applications with external tools, providing data for digital model managing. Strategically correctly designed parametric model can be managed by externally provided information. This paper provides examples of three methods using external data. Presented methods are validated during the use in industrial practice and in the preparation of technical staff at secondary schools, colleges and universities of engineering focus. The main objective of the deployment of presented methods is the acceleration of creation of virtual prototypes digital data of varying complexity while maintaining the accuracy of the corresponding geometric and functional requirements for the final product. At the same time these methods can be used to streamline transfers between different data formats of designer data and to allow interventions into the structure of the model without the use of a particular design engineering applications.

Nitric oxide is an important vasoactive mediator. Changes in NO production, caused by functional variants of both endothelial and inducible NO synthase (eNOS, iNOS), might play a role in portal hypertension. The aim was to study the significance of functional eNOS and iNOS gene variants in cirrhotic patients and their interrelationship to both inflammatory and endothelial activation parameters.One hundred and thirty-two patients with liver cirrhosis (age 36-72 years) and 101 controls were examined for functional variants of eNOS (E298D, 27bpintr4, 786T/C) and iNOS (R221W, S608L) genes. Inflammatory (IL6, IL8, IL10) and vasoactive (sVCAM-1, E-selectin) cytokines were measured using ELISA kits.The frequency of E298D (GG 12%, GT 41%, TT 47%), 28bpintr4 (AA 6%, AB 28%, BB 66%), 786T/C genotypes (CC 17%, CT 45%, TT 38%), as well as R221W (CC 93%, CT 7%, TT 0%), and S608L (CC 65%, CT 32%, TT 3%) genotypes in cirrhotic patients did not differ from the controls (p0.05 for all comparisons). No relationship was found between the frequency of these genotypes and the severity of portal hypertension, or either inflammatory or vasoactive cytokines. A positive correlation was found between hepatic venous pressure gradient and cytokine concentration: sVCAM-1, IL6, IL8, IL10.Examined eNOS and iNOS variants have no relationship to pathogenesis of liver cirrhosis. Severity of portal hypertension was associated with the changes in endothelial activation.

To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value.A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals.The mean value of HVPG was 16.18 ± 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG10 mmHg and 65% for those with HVPG ≤ 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68).Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

Background Chylothorax is an uncommon medical condition. To the best of our knowledge, there have been no detailed English-language reports dealing with its cytopatholoogic findings and diagnostic pitfalls. Cases A 12-year-old boy, hemodialysis dependent, with congenital nephrotic syndrome due to focal segmental glomerular sclerosis and it failed renal transplant, developed shortness of breath. Physical and radiologic examinations revealed a left pleural effusion. A 7-year-old boy developed shortness of breath, with a subsequent finding of a left pleural effusion. Multiple osteolytic skeletal lesions were found in this patient. Both patients underwent thoracocentesis. Cytologically, both fluids contained many relatively uniform, large lymphoid cells with high nuclear/cytoplasmic (N/C) ratio, condensed chromatin and occasional nucleoli, resembling blasts. Some nuclei were convoluted. Mitotic figures were present. Foamy macrophages were present ill both cases. The differential diagnosis of these populations of cells included a lymphoroliferative disorder. However, the 'mature T-lymphocytic nature of the cells was confirmed by immunobistochemistry performed on cell block preparations, confirming the clinical impression of chylothorax in both cases. The first patient had chylothorax as a result of trauma due to therapeutic interventions (subclavian vein cannulation), in the second patient the chylothorax was a part of Gorbam-Stout syndrome. Conclusion The large T-lymphocytes that are the major cellular component of chylothorax may arouse suspicion of a lymphoproliferative disorder. Attention to the clinical history and immunophenotyping confirm the benign nature of the pleural space fluid. Also, abundant foamy macrophages can be considered a low-power clue to this diagnosis.

Cyclic AMP analogs containing hydrophobic modification of C(8) at the adenine ring such as 8-(4-chlorophenylthio)-cAMP (8-pCPT-cAMP) and 8-(4-chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT-2'-O-methyl-cAMP) can penetrate membranes due to their high lipophilicity and directly activate intracellular cAMP effectors. Therefore, these cAMP analogs have been used in numerous studies, assuming that their effects reflect the consequences of direct activation of cAMP effectors. The present study provides evidence that 8-pCPT-modified cAMP analogs and their corresponding putative hydrolysis products (8-(4-chlorophenylthio)-adenosine (8-pCPT-ado) and 8-(4-chlorophenylthio)-2'-O-methyl-adenosine (8-pCPT-2'-O-methyl-ado)) inhibit the equilibrative nucleoside transporter 1 (ENT1). In PC12 cells, in which nucleoside transport strongly depended on ENT1, 8-pCPT-ado, 8-pCPT-2'-O-methyl-ado, and, to a smaller extent, 8-pCPT-2'-O-methyl-cAMP caused an increase of protein kinase A substrate motif phosphorylation and anti-apoptotic effect by an A(2A) adenosine receptor (A(2A)R)-dependent mechanism. In contrast, the effects of 8-pCPT-cAMP were mainly A(2A)R-independent. In HEK 293 showing little endogenous ENT1-dependent nucleoside transport, transfection of ENT1 conferred A(2A)R-dependent increase in protein kinase A substrate motif phosphorylation. Together, the data of the present study indicate that inhibition of ENT1 and activation of adenosine receptors have to be considered when interpreting the effects of 8-pCPT-substituted cAMP/adenosine analogs.

Chyothorax is an uncommon medical condition. To the best of our knowledge, there have been no detailed English-language report dealing with its cytopathologic findings and diagnostic pitfallsA 12-year-old boy, hemodialysis dependent, with congenital nephrotic syndrome due to focal segmental glomerular sclerosis and a failed renal transplant, developed shortness of breath. Physical and radiologic examinations revealed a left pleural effusion. A 7-year-old boy developed shortness of breath, with a subsequent finding of a left pleural effusion. Multiple osteolytic skeletal lesions were found in this patient. Both patients underwent thoracocentesis. Cytologically, both fluids contained many relatively uniform, large lymphoid cells with high nuclear/cytoplasmic (N/C) ratio, condensed chromatin and occasional nucleoli, resembling blasts. Some nuclei were convoluted. Mitotic figures were present. Foamy macrophages were present in both cases. The differential diagnosis of these populations of cells included a lymphoproliferative disorder. However, the mature T-lymphocytic nature of the cells was confirmed by immunohistochemistry performed on cell block preparations, confirming the clinical impression of chylothorax in both cases. The first patient had chylothorax as a result of trauma due to therapeutic interventions (subclavian vein cannulation), in the second patient the chylothorax was a part of Gorham-Stout syndrome.The large T-lymphocytes that are the major cellular component of chylothorax may arouse suspicion of a lymphoproliferative disorder. Attention to the clinical history and immunophenotyping confirm the benign nature of the pleural space fluid. Also, abundant foamy macrophages can be considered a low-power clue to this diagnosis.

Background Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of a metabolic syndrome. To date, liver biopsy has been the gold standard used to differentiate between simple steatosis and steatohepatitis/fibrosis. Our aim was to compare the relevance of serum non-invasive parameters and scoring systems in the staging of liver fibrosis and non-alcoholic steatohepatitis (NASH) in patients with NAFLD. Methods and Findings A total of 112 consecutive patients diagnosed with NAFLD were included. A liver biopsy was performed on 56 patients. The Kleiner score was used for the staging and grading of the histology. Non-invasive parameters for fibrosis (hyaluronic acid; AST/ALT; fibrosis scoring indexes OELF, ELF, BARD score, APRI, NAFLD fibrosis score); and inflammation (M30 and M65 cytokeratin-18 fragments) were measured and calculated. The same analyses were performed in 56 patients diagnosed with NAFLD, who were not indicated for liver biopsy. Based on the liver histology, NASH was diagnosed in 38 patients; simple steatosis in 18 patients. A cut-off value of 750 U/L of serum M65 discriminated patients with and without NASH with a 80% sensitivity and 82% specificity (95% CI:57–95). Fibrosis stage F0–F2 was present in 39 patients; F3–F4 in 17 patients. Serum concentrations of hyaluronic acid were higher in patients with advanced fibrosis (p