AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of t...AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration.There was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.展开更多
AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and muc...AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.展开更多
AIM: Transforming growth factor (TGF)-β1, metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP)-I are considered predictive biomarkers of chronic hepatitis activity and fibrosis.The aim of this study was to evalu...AIM: Transforming growth factor (TGF)-β1, metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP)-I are considered predictive biomarkers of chronic hepatitis activity and fibrosis.The aim of this study was to evaluate the effect of lamivudine treatment on the plasma levels of these peptides in patients with chronic hepatitis B.METHODS: TGF-β1, MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 40 patients treated with lamivudine for 48 wk. Elimination of HBV-DNA and HBV antigens was evaluated 24 wk after treatment completion.RESULTS: Baseline TGF-β1(29.6±2.2 ng/mL) and TIMP-1(1 578±93 ng/mL) significantly exceeded normal values(18.3±1.6 ng/mL and 1 102±67 ng/mL respectively). Lamivudine treatment resulted in a significant decrease of TGF-β1 and TIMP-1 during treatment with an increase after 24 wk of treatment. Pretreatment MMP-1 levels (6.7±0.7 ng/mL) were significantly lower than normal values (11.9±0.9 ng/mL) and increased during treatment and follow-up. A significant correlation was noted between TGF-β1 or TIMP-1 and aminotransferases as well as fibrosis scored in liver biopsy specimens. There were no statistically significant differences of TGF-β1, TIMP-1 and MMP-1 between four groups at baseline, 24 and 48 wk of treatment. TGF-β1 and TIMP-1 levels increased significantly in non-responders and normalized in responders at wk 72. MMP-1 also normalized in responders and decreased to values significantly lower than normal in non-responders.CONCLUSION: These findings support the role of TGF-β1,TIMP-1 and MMP-1 in the pathogenesis of chronic hepatitis B.Because of their association with hepatic injury and antiviral treatment efficacy, determination of these peptides may be useful in disease management.展开更多
AIM： To evaluate the effect of antiviral treatment on plasma levels of transforming growth factor-β1 （TGF-β1）, metalloproteinase 1 （MMP-1）, and tissue inhibitor of metaUoproteinase-1 （TIMP-1） in patients with...AIM： To evaluate the effect of antiviral treatment on plasma levels of transforming growth factor-β1 （TGF-β1）, metalloproteinase 1 （MMP-1）, and tissue inhibitor of metaUoproteinase-1 （TIMP-1） in patients with chronic hepatitis C. METHODS： TGF-β1, MMP-1, and TIMP-1 plasma concentrations were measured by an enzyme immunoassay in 28 patients, during 48 wk of treatment with pegylated interferon-alpha 2b （PEG-IFN-α2b） plus ribavirin （RBV） and after 24 wk of follow-up. Patients were divided into two groups： responders （R） and non-responders （NR） related to achieved sustained virologic response. Normal values were evaluated in plasma samples of 13 healthy volunteers. RESULTS： Baseline plasma concentrations of TGF-β1 and TIMP-1 （30.9±3.7 and 1 506±61 ng/mL respectively） measured in all subjects significantly exceeded the normal values （TGF-β1： 18.3±1.6 ng/mL and TIMP-1： 1 102±67 ng/mL）. In contrast, pretreatment MMP-1 mean level （6.5±0.9 ng/mL） was significantly lower than normal values （11.9±0.9 ng/mL）. Response to the treatment was observed in 12 patients （43%）. TGF-β1 mean concentration measured during the treatment phase decreased to the control level in both groups. However at wk 72, values of NR patients increased and became significantly higher than in R group. TIMP-1 concentrations in R group decreased during the treatment to the level similar to normal. In NR group, TIMP-1 remained significantly elevated during treatment and follow-up phase and significant difference between both groups was demonstrated at wk 48 and 72. MMP-1 levels were significantly decreased in both groups at baseline. Treatment caused rise of its concentration only in the R group, whereas values in NR group remained on the level similar to baseline. Statistically significant difference between groups was noted at wk 48 and 72. CONCLUSION： These findings support the usefulness of TGF-β1, TIMP-1, and MMP-1 in the management of chronic hepatitis C. Elevated TIMP-1 and l展开更多
The tight focusing properties of a radially polarized Gaussian beam with a nested pair of vortices having a radial wave front distribution are investigated theoretically by the vector diffraction theory. The results s...The tight focusing properties of a radially polarized Gaussian beam with a nested pair of vortices having a radial wave front distribution are investigated theoretically by the vector diffraction theory. The results show that the optical intensity in the focal region can be altered considerably by changing the location of the vortices nested in a radially polarized Gaussian beam. It is noted that focal evolution from one annular focal pattern to a highly confined focal spot in the transverse direction is observed corresponding to the change in the location of the optical vortices in the input plane. It is also observed that the generated focal hole or spot lead to a focal shift along the optical axis remarkably under proper radial phase modulation. Hence the proposed system may be applied to construct tunable optical traps for both high and low refractive index particles.展开更多
Three-dimensional(3D)printing is an emerging technique that has shown promising success in engineering human tissues in recent years.Further development of vatphotopolymerization printing modalities has significantly ...Three-dimensional(3D)printing is an emerging technique that has shown promising success in engineering human tissues in recent years.Further development of vatphotopolymerization printing modalities has significantly enhanced the complexity level for 3D printing of various functional structures and components.Similarly,the development of microfluidic chip systems is an emerging research sector with promising medical applications.This work demonstrates the coupling of a digital light processing(DLP)printing procedure with a microfluidic chip system to produce size-tunable,3D-printable porosities with narrow pore size distributions within a gelatin methacryloyl(GelMA)hydrogel matrix.It is found that the generation of size-tunable gas bubbles trapped within an aqueous GelMA hydrogel-precursor can be controlled with high precision.Furthermore,the porosities are printed in two-dimensional(2D)as well as in 3D using the DLP printer.In addition,the cytocompatibility of the printed porous scaffolds is investigated using fibroblasts,where high cell viabilities as well as cell proliferation,spreading,and migration are confirmed.It is anticipated that the strategy is widely applicable in a range of application areas such as tissue engineering and regenerative medicine,among others.展开更多
AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine ...AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well tolerated and safe in patiente with renal insuff展开更多
In this study, powder metallurgy methods were used to fabricate Mg-7.5Li-3Al-Zn alloys from repowdered extruded alloys. Extruded alloys were powdered using ultrasonic atomization, and then laser powder bed fusion(LPBF...In this study, powder metallurgy methods were used to fabricate Mg-7.5Li-3Al-Zn alloys from repowdered extruded alloys. Extruded alloys were powdered using ultrasonic atomization, and then laser powder bed fusion(LPBF) and pulse plasma sintering(PPS) were used to consolidate the bulk materials. A comparison of the properties of the fabricated alloys with those of a conventionally extruded one was carried out using methods that characterized the microstructure and corrosion resistance. When compared to their conventionally extruded counterpart, LPBF and PPS materials exhibited refined microstructures with low enrichment in Al Li and coarse Al, Zn, Mn precipitates. The main drawback of the LPBF alloy, printed for the needs of this study, was its porosity, which had a negative effect on its corrosion. The presence of unrecrystallized particle boundaries in the PPS alloy was also unbeneficial with regard to corrosion. The advantage of the LPBF and PPS processes was the ability to change the proportion of α(Mg) to β(Li), which when the complete consolidation of the material is achievable, may increase the corrosion resistance of dual-structured Mg-Li alloys. The results show that powder metallurgy routes have a wide potential to be used for the manufacture of Mg-Li based alloys.展开更多
AIM:To provide the clinical and epidemiological data of inflammatory bowel disease (IBD) patients of North-Eastern Poland. METHODS: A total of 248 IBD patients diagnosed and hospitalized in the Department of Infectiou...AIM:To provide the clinical and epidemiological data of inflammatory bowel disease (IBD) patients of North-Eastern Poland. METHODS: A total of 248 IBD patients diagnosed and hospitalized in the Department of Infectious Diseases in Bialystok between 1990 and 2003 were included in the study. We analyzed age, sex, education, characteristics of job, type of the environment, discontinuation of employment due to IBD, colitis extent, need of surgical treatment, and coexistence of other diseases. RESULTS: Two hundred and thirty-three IBD patients (94%) were diagnosed as ulcerative colitis (DC), and only 15 (6%) were diagnosed as Crohn's disease (CD). Patients with CD were significantly younger at the time of diagnosis and male predominance was observed. The mean age of the patients at the time UC diagnosis was 44.9±1.1 years. Histogram of the age of patients showed the characteristic biphasic distribution with two peaks between 20 and 40 years and between 60 and 70 years. The predominant form of UC was left sided colitis, which affected almost 80% of the studied population. The most extensive form - pancolitis was present in 34 patients (15%). Only 6% of UC patients required surgery, whereas 36% of CD patients underwent surgery (P<0.005). Among coexisting disorders, cholelithiasis was the most prevalent and demonstrated in 35 patients (14%), pulmonary disorders were diagnosed in 2%, and psoriasis in 1.4%. Since 1998, the number of admitted IBD patients has slightly increased. CONCLUSION: Occurrence of UC in Poland is much higher than that of CD. The majority of UC cases are diagnosed in young people (20-40 years) with the predominance of male patients. The most common clinical form of UC is left sided colitis.展开更多
Hepatitis C virus （HCV） infection affects 180 million people worldwide with the predominant prevalence being infection with genotype 1, followed by genotypes 2 and 3. Standard anti-HCV therapy currently aims to enha...Hepatitis C virus （HCV） infection affects 180 million people worldwide with the predominant prevalence being infection with genotype 1, followed by genotypes 2 and 3. Standard anti-HCV therapy currently aims to enhance natural immune responses to the virus, whereas new therapeutic concepts directly target HCV RNA and viral enzymes or influence host-virus interactions. Novel treatment options now in development are focused on inhibitors of HCV- specific enzymes, NS3 protease and NS5B polymerase. These agents acting in concert represent the concept of specifically targeted antiviral therapy for HCV （STAT-C）. STAT-C is an attractive strategy in which the main goal is to increase the effectiveness of antiviral responses across all genotypes, with shorter treatment duration and better tolerability. However, the emergence of resistant mutations that limit the use of these compounds in monotherapy complicates the regimens. Thus, a predictable scenario for HCV treatment in the future will be combinations of drugs with distinct mechanisms of action. For now, it seems that interferon will remain a fundamental component of any new anti-HCV therapeutic regimens in the near future; therefore, there is pressure to develop forms of interferon that are more effective, less toxic, and more convenient than pegylated interferon.展开更多
AIM: To assess serum concentrations of prohepcidin in chronic hepatitis C individuals and evaluate their associations with disease activity and efficacy of pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. METHO...AIM: To assess serum concentrations of prohepcidin in chronic hepatitis C individuals and evaluate their associations with disease activity and efficacy of pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. METHODS: Prohepcidin was measured in sera of 53 chronic hepatitis C patients. Concentrations of prohepcidin and other iron metabolism markers were analyzed at 9 time points before, during and after the end of antiviral therapy. RESULTS: In hepatitis C virus (HCV) genotype 1-infected individuals, a gradual decrease of prohepcidin during antiviral therapy was observed in responders (88.8 ± 14.7 ng/mL before therapy vs 60.6 ± 0.3 ng/mL in the 48th wk, P = 0.04). In contrast, no decrease was observed in non-responders. A similar association was observed in HCV genotype 3a individuals, with a statistically significant decline in serum prohepcidin only in the responder group (99.5 ± 5.2 ng/mL at baseline vs 72.7 ± 6.1 ng/mL in the 24th wk, P = 0.01). Moreover, HCVRNA at week 12 of therapy was positively correlated with baseline (R = 0.63, P < 0.005) and week 12 (R = 0.60, P = 0.01) serum prohepcidin concentrations in HCV genotype 1 infection. CONCLUSION: Successful PEG-IFN/RBV therapy results in a decline of serum prohepcidin concentration in chronic hepatitis C, which may suggest a direct effect of HCV on iron metabolism at the prohormonal level of hepcidin.展开更多
We present a lensless projection of color images based on computer-generated Fourier holograms. Amplitude and phase modulation of three primary-colored laser beams is performed by a matched pair of spatial light modul...We present a lensless projection of color images based on computer-generated Fourier holograms. Amplitude and phase modulation of three primary-colored laser beams is performed by a matched pair of spatial light modulators. The main advantage of the complex light modulation is the lack of iterative phase retrieval techniques. The advantage is the lack of speckles in the projected images. Experimental results are given and compared with the outcome of classical phase-only modulation.展开更多
A novel metal matrix composites(MMC)with Mg matrix reinforced with natural filler in the form of Didymosphenia geminata frustules(algae with distinctive siliceous shells)are presented in this work.Pulse plasma sinteri...A novel metal matrix composites(MMC)with Mg matrix reinforced with natural filler in the form of Didymosphenia geminata frustules(algae with distinctive siliceous shells)are presented in this work.Pulse plasma sintering(PPS)was used to manufacture Mg-based composites with 1,5 and 10 vol.%ceramic filler.As a reference,pure Mg was sintered.The results show that the addition of 1 vol.%Didymosphenia geminata frustules to the Mg matrix increases its corrosion resistance by supporting passivation reactions,and do not affect the morphology of L929 fibroblasts.Addition of 5 vol.%the filler does not cause cytotoxic effects,but it supports microgalvanic reactions leading to the greater corrosion rate.Higher content than 5 vol.%the filler causes significant microgalvanic corrosion,as well as increases cytotoxicity due to the greater micro-galvanic effect of the composites containing 10 and 15 vol.%diatoms.The results of contact angle measurements show the hydrophilic character of the investigated materials,with slightly increase in numerical values with addition of amount of ceramic reinforcement.The addition of Didymosphenia geminata frustules causes changes in a thermo-elastic properties such as mean apparent value of coefficient of thermal expansion(CTE)and thermal conductivity(λ).The addition of siliceous reinforcement resulted in a linear decrease of CTE and reduction in thermal conductivity over the entire temperature range.With the increasing addition of Didymosphenia geminata frustules,an increase in strength with a decrease in compressive strain is observed.In all composites an increase in microhardness was attained.The results clearly indicate that filler in the form of Didymosphenia geminata frustules may significantly change the most important properties of pure Mg,indicating its wide potential in the application of Mg-based composites with a special focus on biomedical use.展开更多
Tight focusing properties of an azimuthally polarized Gaussian beam with a pair of vortices through a dielectric interface is theoretically investigated by vector diffraction theory. For the incident beam with a pair ...Tight focusing properties of an azimuthally polarized Gaussian beam with a pair of vortices through a dielectric interface is theoretically investigated by vector diffraction theory. For the incident beam with a pair of vortices of opposite topological charges, the vortices move toward each other, annihilate and revive in the vicinity of focal plane, which results in the generation of many novel focal patterns. The usable focal structures generated through the tight focusing of the double-vortex beams may find applications in micro-particle trapping, manipulation, and material processing, etc.展开更多
Magnesium (Mg) alloys have become a potential material for orthopedic implants due to their unnecessary implant removal, biocompatibility, and mechanical integrity until fracture healing. This study examined the in vi...Magnesium (Mg) alloys have become a potential material for orthopedic implants due to their unnecessary implant removal, biocompatibility, and mechanical integrity until fracture healing. This study examined the in vitro and in vivo degradation of an Mg fixation screw composed of Mg-0.45Zn-0.45Ca (ZX00, in wt.%). With ZX00 human-sized implants, in vitro immersion tests up to 28 days under physiological conditions, along with electrochemical measurements were performed for the first time. In addition, ZX00 screws were implanted in the diaphysis of sheep for 6, 12, and 24 weeks to assess the degradation and biocompatibility of the screws in vivo. Using scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), micro-computed tomography (μCT), X-ray photoelectron spectroscopy (XPS), and histology, the surface and cross-sectional morphologies of the corrosion layers formed, as well as the bone-corrosion-layer-implant interfaces, were analyzed. Our findings from in vivo testing demonstrated that ZX00 alloy promotes bone healing and the formation of new bone in direct contact with the corrosion products. In addition, the same elemental composition of corrosion products was observed for in vitro and in vivo experiments;however, their elemental distribution and thicknesses differ depending on the implant location. Our findings suggest that the corrosion resistance was microstructure-dependent. The head zone was the least corrosion-resistant, indicating that the production procedure could impact the corrosion performance of the implant. In spite of this, the formation of new bone and no adverse effects on the surrounding tissues demonstrated that the ZX00 is a suitable Mg-based alloy for temporary bone implants.展开更多
AIM. To evaluate bhe activity of apoptosis in liver tissue and explore its possible association with hepatic necroinflammarion and fibrosis as well as serum hepatitis C virus （HCV） load. METHODS： The studied popula...AIM. To evaluate bhe activity of apoptosis in liver tissue and explore its possible association with hepatic necroinflammarion and fibrosis as well as serum hepatitis C virus （HCV） load. METHODS： The studied population included 50 chronic hepatitis C patients （20 women and 30 men, aged 18-66 years）. HCV-RNA quantification was performed by two-step real-time quantitative RT-PCR mebhod using the TaqMan technology （reagents of Applera Corporation firm, USA）. The morphology of liver tissue was assessed descriptively and scored （necroinflammatory activity and fibrosis）. The early apoptosis activity in liver tissue was examined by ssDNA apoptosis ELISA kit, （Chemicon, Germany）. RESULTS： The correlation between apoptosis and fibrosis in liver tissue was observed. High intensification of apoptosis was proportional to the increase of fibrosis （ssDNA： 16.65×10^-5μg/g; 12.71×10^-5μg/g）, however, bhis difference was not statistically significant （P〉0.05）. Activity of apoptosis in the liver tissue, expressed by ssDNA concentration did not depend on hepatic necroinflammatory changes, HCVRNA viral load, ALT, and AST activity as well as prothrombin time and INR index. CONCLUSION： Fibrosis in the tissue is closely associated with early apoptosis in HCV-infected patients.展开更多
BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus(HCV)infection dates back to the introduction of direct-acting antivirals(DAAs).The increase in efficacy was most pronounced in patients...BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus(HCV)infection dates back to the introduction of direct-acting antivirals(DAAs).The increase in efficacy was most pronounced in patients infected with genotype(GT)1b,as this was the most poorly responsive population to treatment during the interferon era.AIM To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological response.METHODS This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 database.Treatment effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses(SVR).Assessment of the safety was based on the evaluation of the course of therapy,the occurrence of adverse events including serious ones,deaths during treatment and in the post 12-wk follow-up period.RESULTS The studied population consisted of 11385 patients with a mean age of 53±14.8 years and a female predominance(53.4%).The majority of them were treatment-naïve(74.6%)and patients with cirrhosis accounted for 24.3%.Of the DAA regimens used,76.9%were GT-specific with ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin being the most used option(32.4%).A total of 10903 patients responded to treatment resulting in a 98.1%in the per-protocol analysis after excluding 273 patients without SVR data.The effectiveness of all regimens exceeded 90%and the highest SVR of 98.9%was achieved in patients treated with a combination of glecaprevir/pibrentasvir.Logistic regression analyses showed that the virologic response was independently associated with female sex[odds ratio(OR)=1.67],absence of decompensated cirrhosis at baseline(OR=2.42)and higher baseline platelets(OR=1.004 per 1000/μL increase),while the presence of human immunodeficiency virus(HIV)coinfection significantly decreased the odds of response(OR=0.39).About 95%-100%of patie展开更多
BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have...BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine l展开更多
文摘AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration.There was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.
文摘AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.
文摘AIM: Transforming growth factor (TGF)-β1, metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP)-I are considered predictive biomarkers of chronic hepatitis activity and fibrosis.The aim of this study was to evaluate the effect of lamivudine treatment on the plasma levels of these peptides in patients with chronic hepatitis B.METHODS: TGF-β1, MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 40 patients treated with lamivudine for 48 wk. Elimination of HBV-DNA and HBV antigens was evaluated 24 wk after treatment completion.RESULTS: Baseline TGF-β1(29.6±2.2 ng/mL) and TIMP-1(1 578±93 ng/mL) significantly exceeded normal values(18.3±1.6 ng/mL and 1 102±67 ng/mL respectively). Lamivudine treatment resulted in a significant decrease of TGF-β1 and TIMP-1 during treatment with an increase after 24 wk of treatment. Pretreatment MMP-1 levels (6.7±0.7 ng/mL) were significantly lower than normal values (11.9±0.9 ng/mL) and increased during treatment and follow-up. A significant correlation was noted between TGF-β1 or TIMP-1 and aminotransferases as well as fibrosis scored in liver biopsy specimens. There were no statistically significant differences of TGF-β1, TIMP-1 and MMP-1 between four groups at baseline, 24 and 48 wk of treatment. TGF-β1 and TIMP-1 levels increased significantly in non-responders and normalized in responders at wk 72. MMP-1 also normalized in responders and decreased to values significantly lower than normal in non-responders.CONCLUSION: These findings support the role of TGF-β1,TIMP-1 and MMP-1 in the pathogenesis of chronic hepatitis B.Because of their association with hepatic injury and antiviral treatment efficacy, determination of these peptides may be useful in disease management.
文摘AIM： To evaluate the effect of antiviral treatment on plasma levels of transforming growth factor-β1 （TGF-β1）, metalloproteinase 1 （MMP-1）, and tissue inhibitor of metaUoproteinase-1 （TIMP-1） in patients with chronic hepatitis C. METHODS： TGF-β1, MMP-1, and TIMP-1 plasma concentrations were measured by an enzyme immunoassay in 28 patients, during 48 wk of treatment with pegylated interferon-alpha 2b （PEG-IFN-α2b） plus ribavirin （RBV） and after 24 wk of follow-up. Patients were divided into two groups： responders （R） and non-responders （NR） related to achieved sustained virologic response. Normal values were evaluated in plasma samples of 13 healthy volunteers. RESULTS： Baseline plasma concentrations of TGF-β1 and TIMP-1 （30.9±3.7 and 1 506±61 ng/mL respectively） measured in all subjects significantly exceeded the normal values （TGF-β1： 18.3±1.6 ng/mL and TIMP-1： 1 102±67 ng/mL）. In contrast, pretreatment MMP-1 mean level （6.5±0.9 ng/mL） was significantly lower than normal values （11.9±0.9 ng/mL）. Response to the treatment was observed in 12 patients （43%）. TGF-β1 mean concentration measured during the treatment phase decreased to the control level in both groups. However at wk 72, values of NR patients increased and became significantly higher than in R group. TIMP-1 concentrations in R group decreased during the treatment to the level similar to normal. In NR group, TIMP-1 remained significantly elevated during treatment and follow-up phase and significant difference between both groups was demonstrated at wk 48 and 72. MMP-1 levels were significantly decreased in both groups at baseline. Treatment caused rise of its concentration only in the R group, whereas values in NR group remained on the level similar to baseline. Statistically significant difference between groups was noted at wk 48 and 72. CONCLUSION： These findings support the usefulness of TGF-β1, TIMP-1, and MMP-1 in the management of chronic hepatitis C. Elevated TIMP-1 and l
文摘The tight focusing properties of a radially polarized Gaussian beam with a nested pair of vortices having a radial wave front distribution are investigated theoretically by the vector diffraction theory. The results show that the optical intensity in the focal region can be altered considerably by changing the location of the vortices nested in a radially polarized Gaussian beam. It is noted that focal evolution from one annular focal pattern to a highly confined focal spot in the transverse direction is observed corresponding to the change in the location of the optical vortices in the input plane. It is also observed that the generated focal hole or spot lead to a focal shift along the optical axis remarkably under proper radial phase modulation. Hence the proposed system may be applied to construct tunable optical traps for both high and low refractive index particles.
基金National Science Centre Poland(NCN),Grant/Award Number:2020/37/B/ST8/02167European Union’s Horizon 2020 research and innovation program,Grant/Award Number:813786+2 种基金National Institutes of Health,Grant/Award Number:R21EB025270National Science Foundation,Grant/Award Number:CBET-EBMS-1936105Brigham Research Institute。
文摘Three-dimensional(3D)printing is an emerging technique that has shown promising success in engineering human tissues in recent years.Further development of vatphotopolymerization printing modalities has significantly enhanced the complexity level for 3D printing of various functional structures and components.Similarly,the development of microfluidic chip systems is an emerging research sector with promising medical applications.This work demonstrates the coupling of a digital light processing(DLP)printing procedure with a microfluidic chip system to produce size-tunable,3D-printable porosities with narrow pore size distributions within a gelatin methacryloyl(GelMA)hydrogel matrix.It is found that the generation of size-tunable gas bubbles trapped within an aqueous GelMA hydrogel-precursor can be controlled with high precision.Furthermore,the porosities are printed in two-dimensional(2D)as well as in 3D using the DLP printer.In addition,the cytocompatibility of the printed porous scaffolds is investigated using fibroblasts,where high cell viabilities as well as cell proliferation,spreading,and migration are confirmed.It is anticipated that the strategy is widely applicable in a range of application areas such as tissue engineering and regenerative medicine,among others.
文摘AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well tolerated and safe in patiente with renal insuff
文摘In this study, powder metallurgy methods were used to fabricate Mg-7.5Li-3Al-Zn alloys from repowdered extruded alloys. Extruded alloys were powdered using ultrasonic atomization, and then laser powder bed fusion(LPBF) and pulse plasma sintering(PPS) were used to consolidate the bulk materials. A comparison of the properties of the fabricated alloys with those of a conventionally extruded one was carried out using methods that characterized the microstructure and corrosion resistance. When compared to their conventionally extruded counterpart, LPBF and PPS materials exhibited refined microstructures with low enrichment in Al Li and coarse Al, Zn, Mn precipitates. The main drawback of the LPBF alloy, printed for the needs of this study, was its porosity, which had a negative effect on its corrosion. The presence of unrecrystallized particle boundaries in the PPS alloy was also unbeneficial with regard to corrosion. The advantage of the LPBF and PPS processes was the ability to change the proportion of α(Mg) to β(Li), which when the complete consolidation of the material is achievable, may increase the corrosion resistance of dual-structured Mg-Li alloys. The results show that powder metallurgy routes have a wide potential to be used for the manufacture of Mg-Li based alloys.
文摘AIM:To provide the clinical and epidemiological data of inflammatory bowel disease (IBD) patients of North-Eastern Poland. METHODS: A total of 248 IBD patients diagnosed and hospitalized in the Department of Infectious Diseases in Bialystok between 1990 and 2003 were included in the study. We analyzed age, sex, education, characteristics of job, type of the environment, discontinuation of employment due to IBD, colitis extent, need of surgical treatment, and coexistence of other diseases. RESULTS: Two hundred and thirty-three IBD patients (94%) were diagnosed as ulcerative colitis (DC), and only 15 (6%) were diagnosed as Crohn's disease (CD). Patients with CD were significantly younger at the time of diagnosis and male predominance was observed. The mean age of the patients at the time UC diagnosis was 44.9±1.1 years. Histogram of the age of patients showed the characteristic biphasic distribution with two peaks between 20 and 40 years and between 60 and 70 years. The predominant form of UC was left sided colitis, which affected almost 80% of the studied population. The most extensive form - pancolitis was present in 34 patients (15%). Only 6% of UC patients required surgery, whereas 36% of CD patients underwent surgery (P<0.005). Among coexisting disorders, cholelithiasis was the most prevalent and demonstrated in 35 patients (14%), pulmonary disorders were diagnosed in 2%, and psoriasis in 1.4%. Since 1998, the number of admitted IBD patients has slightly increased. CONCLUSION: Occurrence of UC in Poland is much higher than that of CD. The majority of UC cases are diagnosed in young people (20-40 years) with the predominance of male patients. The most common clinical form of UC is left sided colitis.
文摘Hepatitis C virus （HCV） infection affects 180 million people worldwide with the predominant prevalence being infection with genotype 1, followed by genotypes 2 and 3. Standard anti-HCV therapy currently aims to enhance natural immune responses to the virus, whereas new therapeutic concepts directly target HCV RNA and viral enzymes or influence host-virus interactions. Novel treatment options now in development are focused on inhibitors of HCV- specific enzymes, NS3 protease and NS5B polymerase. These agents acting in concert represent the concept of specifically targeted antiviral therapy for HCV （STAT-C）. STAT-C is an attractive strategy in which the main goal is to increase the effectiveness of antiviral responses across all genotypes, with shorter treatment duration and better tolerability. However, the emergence of resistant mutations that limit the use of these compounds in monotherapy complicates the regimens. Thus, a predictable scenario for HCV treatment in the future will be combinations of drugs with distinct mechanisms of action. For now, it seems that interferon will remain a fundamental component of any new anti-HCV therapeutic regimens in the near future; therefore, there is pressure to develop forms of interferon that are more effective, less toxic, and more convenient than pegylated interferon.
基金Supported by A Scientific Grant from the Medical University in Bialystok, No. 356978-La Polpharma Foundation For Development of Polish Pharmacy and Medicine
文摘AIM: To assess serum concentrations of prohepcidin in chronic hepatitis C individuals and evaluate their associations with disease activity and efficacy of pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. METHODS: Prohepcidin was measured in sera of 53 chronic hepatitis C patients. Concentrations of prohepcidin and other iron metabolism markers were analyzed at 9 time points before, during and after the end of antiviral therapy. RESULTS: In hepatitis C virus (HCV) genotype 1-infected individuals, a gradual decrease of prohepcidin during antiviral therapy was observed in responders (88.8 ± 14.7 ng/mL before therapy vs 60.6 ± 0.3 ng/mL in the 48th wk, P = 0.04). In contrast, no decrease was observed in non-responders. A similar association was observed in HCV genotype 3a individuals, with a statistically significant decline in serum prohepcidin only in the responder group (99.5 ± 5.2 ng/mL at baseline vs 72.7 ± 6.1 ng/mL in the 24th wk, P = 0.01). Moreover, HCVRNA at week 12 of therapy was positively correlated with baseline (R = 0.63, P < 0.005) and week 12 (R = 0.60, P = 0.01) serum prohepcidin concentrations in HCV genotype 1 infection. CONCLUSION: Successful PEG-IFN/RBV therapy results in a decline of serum prohepcidin concentration in chronic hepatitis C, which may suggest a direct effect of HCV on iron metabolism at the prohormonal level of hepcidin.
基金supported by the Polish Ministry of Science and Higher Education under Grant No. IP 2010023570
文摘We present a lensless projection of color images based on computer-generated Fourier holograms. Amplitude and phase modulation of three primary-colored laser beams is performed by a matched pair of spatial light modulators. The main advantage of the complex light modulation is the lack of iterative phase retrieval techniques. The advantage is the lack of speckles in the projected images. Experimental results are given and compared with the outcome of classical phase-only modulation.
基金Izabela B.Zgłobicka acknowledges the funding provided by National Science Center for providing financial support to project Metal Matrix Composites with natural filler(Grant No.2018/31/D/ST8/00890).The authors are grateful to Dr Matt P.Ashworth from the University of Texas at Austin(USA)for critically reading the manuscript and correcting the language.
文摘A novel metal matrix composites(MMC)with Mg matrix reinforced with natural filler in the form of Didymosphenia geminata frustules(algae with distinctive siliceous shells)are presented in this work.Pulse plasma sintering(PPS)was used to manufacture Mg-based composites with 1,5 and 10 vol.%ceramic filler.As a reference,pure Mg was sintered.The results show that the addition of 1 vol.%Didymosphenia geminata frustules to the Mg matrix increases its corrosion resistance by supporting passivation reactions,and do not affect the morphology of L929 fibroblasts.Addition of 5 vol.%the filler does not cause cytotoxic effects,but it supports microgalvanic reactions leading to the greater corrosion rate.Higher content than 5 vol.%the filler causes significant microgalvanic corrosion,as well as increases cytotoxicity due to the greater micro-galvanic effect of the composites containing 10 and 15 vol.%diatoms.The results of contact angle measurements show the hydrophilic character of the investigated materials,with slightly increase in numerical values with addition of amount of ceramic reinforcement.The addition of Didymosphenia geminata frustules causes changes in a thermo-elastic properties such as mean apparent value of coefficient of thermal expansion(CTE)and thermal conductivity(λ).The addition of siliceous reinforcement resulted in a linear decrease of CTE and reduction in thermal conductivity over the entire temperature range.With the increasing addition of Didymosphenia geminata frustules,an increase in strength with a decrease in compressive strain is observed.In all composites an increase in microhardness was attained.The results clearly indicate that filler in the form of Didymosphenia geminata frustules may significantly change the most important properties of pure Mg,indicating its wide potential in the application of Mg-based composites with a special focus on biomedical use.
文摘Tight focusing properties of an azimuthally polarized Gaussian beam with a pair of vortices through a dielectric interface is theoretically investigated by vector diffraction theory. For the incident beam with a pair of vortices of opposite topological charges, the vortices move toward each other, annihilate and revive in the vicinity of focal plane, which results in the generation of many novel focal patterns. The usable focal structures generated through the tight focusing of the double-vortex beams may find applications in micro-particle trapping, manipulation, and material processing, etc.
文摘Magnesium (Mg) alloys have become a potential material for orthopedic implants due to their unnecessary implant removal, biocompatibility, and mechanical integrity until fracture healing. This study examined the in vitro and in vivo degradation of an Mg fixation screw composed of Mg-0.45Zn-0.45Ca (ZX00, in wt.%). With ZX00 human-sized implants, in vitro immersion tests up to 28 days under physiological conditions, along with electrochemical measurements were performed for the first time. In addition, ZX00 screws were implanted in the diaphysis of sheep for 6, 12, and 24 weeks to assess the degradation and biocompatibility of the screws in vivo. Using scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), micro-computed tomography (μCT), X-ray photoelectron spectroscopy (XPS), and histology, the surface and cross-sectional morphologies of the corrosion layers formed, as well as the bone-corrosion-layer-implant interfaces, were analyzed. Our findings from in vivo testing demonstrated that ZX00 alloy promotes bone healing and the formation of new bone in direct contact with the corrosion products. In addition, the same elemental composition of corrosion products was observed for in vitro and in vivo experiments;however, their elemental distribution and thicknesses differ depending on the implant location. Our findings suggest that the corrosion resistance was microstructure-dependent. The head zone was the least corrosion-resistant, indicating that the production procedure could impact the corrosion performance of the implant. In spite of this, the formation of new bone and no adverse effects on the surrounding tissues demonstrated that the ZX00 is a suitable Mg-based alloy for temporary bone implants.
文摘AIM. To evaluate bhe activity of apoptosis in liver tissue and explore its possible association with hepatic necroinflammarion and fibrosis as well as serum hepatitis C virus （HCV） load. METHODS： The studied population included 50 chronic hepatitis C patients （20 women and 30 men, aged 18-66 years）. HCV-RNA quantification was performed by two-step real-time quantitative RT-PCR mebhod using the TaqMan technology （reagents of Applera Corporation firm, USA）. The morphology of liver tissue was assessed descriptively and scored （necroinflammatory activity and fibrosis）. The early apoptosis activity in liver tissue was examined by ssDNA apoptosis ELISA kit, （Chemicon, Germany）. RESULTS： The correlation between apoptosis and fibrosis in liver tissue was observed. High intensification of apoptosis was proportional to the increase of fibrosis （ssDNA： 16.65×10^-5μg/g; 12.71×10^-5μg/g）, however, bhis difference was not statistically significant （P〉0.05）. Activity of apoptosis in the liver tissue, expressed by ssDNA concentration did not depend on hepatic necroinflammatory changes, HCVRNA viral load, ALT, and AST activity as well as prothrombin time and INR index. CONCLUSION： Fibrosis in the tissue is closely associated with early apoptosis in HCV-infected patients.
文摘BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus(HCV)infection dates back to the introduction of direct-acting antivirals(DAAs).The increase in efficacy was most pronounced in patients infected with genotype(GT)1b,as this was the most poorly responsive population to treatment during the interferon era.AIM To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological response.METHODS This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 database.Treatment effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses(SVR).Assessment of the safety was based on the evaluation of the course of therapy,the occurrence of adverse events including serious ones,deaths during treatment and in the post 12-wk follow-up period.RESULTS The studied population consisted of 11385 patients with a mean age of 53±14.8 years and a female predominance(53.4%).The majority of them were treatment-naïve(74.6%)and patients with cirrhosis accounted for 24.3%.Of the DAA regimens used,76.9%were GT-specific with ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin being the most used option(32.4%).A total of 10903 patients responded to treatment resulting in a 98.1%in the per-protocol analysis after excluding 273 patients without SVR data.The effectiveness of all regimens exceeded 90%and the highest SVR of 98.9%was achieved in patients treated with a combination of glecaprevir/pibrentasvir.Logistic regression analyses showed that the virologic response was independently associated with female sex[odds ratio(OR)=1.67],absence of decompensated cirrhosis at baseline(OR=2.42)and higher baseline platelets(OR=1.004 per 1000/μL increase),while the presence of human immunodeficiency virus(HIV)coinfection significantly decreased the odds of response(OR=0.39).About 95%-100%of patie
文摘BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine l
