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| 1 | Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity显示文摘AIM: Overexpression of mucosal metalloproteinases (MMP)has been demonstrated recently in inflammatory boweldisease. Their activity can be counterbalanced by the tissueinhibitor of metalloproteinases (TIMP). The aim of this studywas to evaluate the effect of ulcerative colitis (UC) on MMP-1 and TTMP-1 plasma concentrations, as two possiblebiomarkers of the disease activity.METHODS: MMP-1 and TIMP-1 plasma concentrations weremeasured with an enzyme immunoassay in 16 patients withendoscopically confirmed active UC.RESULTS: Plasma concentrations of both MMP-11 (13.7±0.2ng/ml) and TIMP-L (799±140 ng/ml) were significantlyelevated in UC patients in comparison to healthy controls(11.9±0.9 ng/ml and 220±7 ng/ml respectively). There wasno correlation between TIMP-1 and MMP-1 concentrations(r=-0.02). TIMP-1 levels revealed significant positivecorrelations with scored endoscopic degree of mucosai injury,disease activity index and clinical activity index values aswell as C-reactive protein concentration. There was nocorrelation between MMP-1 and laboratory, clinical orendoscopic 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 thedisease activity, demonstrating association with clinical andendoscopic pictures. | Alicja Wiercinska-Drapalo Jerzy Jaroszewicz Robert Flisiak Danuta Prokopowicz | 2003 | World Journal of Gastroenterology2003，9，12： | 21 |
| 2 | Plasma interleukin-18 reflects severity of ulcerative colitis显示文摘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:Il-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 (1 347±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. | Alicja Wiercinska-Drapalo Flobert Flisiak Jerzy Jaroszewicz Danuta Prokopowicz | 2005 | World Journal of Gastroenterology2005，11，4： | 16 |
| 3 | High concentration of antimitochondrial antibodies predicts progressive primary biliary cirrhosis显示文摘AIM: To evaluate the serum concentration of antimitochondrial antibodies (AMAs) as a prognostic indicator of progressive primary biliary cirrhosis (pPBC).METHODS: Serum concentrations of AMA subtypes (anti-M2, anti-M4, and anti-M9), biochemical indices of liver function and Mayo risk factor (MRF) were determined in 30 women with diagnosed primary biliary cirrhosis (PBC) selected among 348 females with elevated alkaline phosphatase but without signs of hepatic decompensation.They were followed up for 5 years for possible development of hepatic decompensation.RESULTS: Anti-M2 concentration was significantly correlated with bilirubin and albumin levels as well as MRF, whereas anti-M4 was significantly correlated with albumin level, prothrombin time and MRF. During the 5-year follow-up, progressive PBC (pPBC) was diagnosed in 3 among 23 patients available for evaluation. These 3patients were positive for both anti-M2 and anti-M4.Anti-M2 serum concentration exceeded 1 300 RU/mL in patients with pPBC and only in 1 among 20 non-progressive PBC persons (5%). Anti-M4 serum concentration exceeded 400 RU/mL in 2 of the progressive patients and none in the non-progressive group. In contrast, anti-M9 serum concentration was below 100 RU/mL in all patients with pPBC, and higher than 100 RU/mL in 11 women (55%)among the non-progressive group.CONCLUSION: Females with elevated alkaline phosphatase and high anti-M2 and anti-M4 concentrations are at a high risk for developing pPBC. Quantitative AMA detection should be considered as a method for early diagnosis of pPBC. | Robert Flisiak Maria Pelszynska Danuta Prokopowicz Magdalena Rogalska Urszula Grygoruk | 2005 | World Journal of Gastroenterology2005，11，36： | 16 |
| 4 | Effect of lamivudine treatment on plasma levels of transforming growth factor β_1,tissue inhibitor of metalloproteinases-1 and metalloproteinase-1 in patients with chronic hepatitis B显示文摘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. | Robert Flisiak Haza Al-Kadasi Jerzy Jaroszewicz Danuta Prokopowicz Iwona Flisiak | 2004 | World Journal of Gastroenterology2004，10，18： | 7 |
| 5 | Effect of pegylated interferon alpha 2b plus ribavirin treatment on plasma transforming growth factor-β1,metalloproteinase-1,and tissue metalloproteinase inhibitor-1 in patients with chronic hepatitis C显示文摘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 metalloproteinase-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-β1and TIMP-1 (30.9±3.7 and 1506±61 ng/mL respectively)measured in all subjects significantly exceeded the normal values (TGF-β1:18.3±1.6 ng/mL and TIMP-1:1102±67 ng/mL). In contrast, pretreatment MMP-1mean 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-β1mean 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-1levels 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 low MMP-1plasma concentrations during antiviral therapy may indicate medication failure. | Robert Flisiak Jerzy Jaroszewicz Tadeusz W Lapiski Iwona Flisiak Danuta Prokopowiczi | 2005 | World Journal of Gastroenterology2005，11，43： | 7 |
| 6 | Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: A European perspective显示文摘 | Jerzy Jaroszewicz Beatriz Calle Serrano Karsten Wursthorn Katja Deterding Jerome Schlue Regina Raupach Robert Flisiak C.-Thomas Bock Michael P. Manns Heiner Wedemeyer Markus Cornberg | 2010 | Journal of Hepatology2010，，4： | 6 |
| 7 | Three-Year Efficacy and Safety of Tenofovir Disoproxil Fumarate Treatment for Chronic Hepatitis B显示文摘 | E. Jenny Heathcote Patrick Marcellin Maria Buti Edward Gane Robert A. De Man Zahary Krastev George Germanidis Samuel S. Lee Robert Flisiak Kelly Kaita Michael Manns Iskren Kotzev Konstantin Tchernev Peter Buggisch Frank Weilert Oya Ovunc Kurdas Mitchell L | 2011 | Gastroenterology2011，，1： | 5 |
| 8 | Role of cannabinoids in chronic liver diseases显示文摘Cannabinoids are a group of compounds acting pri-marily via CB1 and CB2 receptors.The expression of cannabinoid receptors in normal liver is low or absent.However,many reports have proven up-regulation of the expression of CB1 and CB2 receptors in hepatic myofibroblasts and vascular endothelial cells,as well as increased concentration of endocannabinoids in liver in the course of chronic progressive liver diseases.It has been shown that CB1 receptor signalling exerts profibrogenic and proinflammatory effects in liver tis-sue,primarily due to the stimulation of hepatic stellate cells,whereas the activation of CB2 receptors inhibits or even reverses liver fibrogenesis.Similarly,CB1 re-ceptor stimulation contributes to progression of liver steatosis.In end-stage liver disease,the endocannabi-noid system has been shown to contribute to hepatic encephalopathy and vascular effects,such as portal hypertension,splanchnic vasodilatation,relative pe-ripheral hypotension and probably cirrhotic cardiomy-opathy.So far,available evidence is based on cellular cultures or animal models.Clinical data on the effects of cannabinoids in chronic liver diseases are limited.However,recent studies have shown the contribution of cannabis smoking to the progression of liver fibrosis and steatosis.Moreover,controlling CB1 or CB2 signal-ling appears to be an attractive target in managing liver diseases. | Anna Parfieniuk Robert Flisiak | 2008 | World Journal of Gastroenterology2008，14，40： | 5 |
| 9 | Efficiency and safety of lamivudine therapy in patients with chronic HBV infection, dialysis or after kidney transplantation显示文摘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, 7patients 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 patients 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 antiHCV 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% kidneytransplanted 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 effects of lamivudine treatment in studied patients.CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patients withnormal function of kidney. Lamivudine treatment is well tolerated and safe in patients with renal insufficiency undergoing hemodialysis and kidney-transplantation.However, in the latter group, high incidence of YMDD mutation after lamivudine treatment was observed. | Tadeusz Wojciech Lapinski Robert Flisiak Jerzy Jaroszewicz Ma3gorzata Michalewicz Oksana Kowalczuk | 2005 | World Journal of Gastroenterology2005，11，3： | 3 |
| 10 | Epidemiological characteristics of inflammatory bowel disease in North-Eastern Poland显示文摘AIM: To provide the clinical and epidemiological data of inflammatory bowel disease (IBD) patients of NorthEastern 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 (UC), 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. | Alicja Wiercinska-Drapalo Jerzy Jaroszewicz Robert Flisiak Danuta Prokopowicz | 2005 | World Journal of Gastroenterology2005，11，17： | 3 |
| 11 | Signal transduction pathways in liver and the influence of hepatitis C virus infection on their activities显示文摘In liver,the most intensively studied transmembrane and intracellular signal transduction pathways are the Janus kinase signal transduction pathway,the mitogen-activated protein kinases signal transduction pathway,the transforming growth factor β signal transduction pathway,the tumor necrosis factor α signal transduction pathway and the recently discovered sphingolipid signal transduction pathway.All of them are activated by many different cytokines and growth factors.They regulate specific cell mechanisms such as hepatocytes proliferation,growth,differentiation,adhesion,apoptosis,and synthesis and degradation of the extracellular matrix.The replication cycle of hepatitis C virus(HCV) is intracellular and requires signal transduction to the nucleus to regulate transcription of its genes.Moreover,HCV itself,by its structural and non-structural proteins,could influence the activity of the second signal messengers.Thus,the inhibition of the transmembrane and intracellular signal transduction pathways could be a new therapeutic target in chronic hepatitis C treatment. | Magdalena M Dabrowska Anatol Panasiuk Robert Flisiak | 2009 | World Journal of Gastroenterology2009，15，18： | 3 |
| 12 | Specifically targeted antiviral therapy for hepatitis C virus显示文摘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. ? 2007 WJG. All rights reserved. | Anna Parfieniuk Jerzy Jaroszewicz Robert Flisiak | 2007 | World Journal of Gastroenterology2007，13，43： | 2 |
| 13 | Successful antiviral therapy is associated with a decrease of serum prohepcidin in chronic hepatitis C显示文摘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. | Jerzy Jaroszewicz Magdalena Rogalska Iwona Flisiak Robert Flisiak | 2010 | World Journal of Gastroenterology2010，16，14： | 2 |
| 14 | The role of tumor necrosis factor alpha receptors(TNF-alpha) in psoriasis and other skin disorders显示文摘 | Serwin AB Flisiak I Chodynicka B | 2004 | Wiad Lek2004，57，1112： | 1 |
| 15 | Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitisB using HBsAg and HBV DNA levels 显示文摘 | Rijckborst V Hansen BE Cakaloglu Y Ferenci P Tabak F Akdogan M Simon K Akarca US Flisiak R Verhey E Van Vuuren AJ Boucher CA ter Borg MJ Janssen HL | 2010 | Hepatology2010，52，2： | 1 |
| 16 | Plasma transforming growth factor betal, metalloproteinase-I and tissue inhibitor of metalloproteinases-I in acute viral hepatitis type B显示文摘 | Flisiak R JaroszewiczJ Lapinski TW | 2005 | Regul Pept2005，131，13： | 1 |
| 17 | Effect of pso- riasis activity on VEGF and its soluble receptors concen- trations in serum and plaque scales 显示文摘 | Flisiak I Zaniewski P Rogalska M | 2013 | Cytokine2013，61，2： | 1 |
| 18 | Plasma TGF-betal, TIMP- 1, MMP-1 and IL-18 as a combined biomarker of psoriasis activity显示文摘 | Flisiak I Zaniewski P Chodynicka B | 2008 | Biomarkers2008，13，5： | 1 |
| 19 | Long term treatment with tenofovir disoproxil fumarate for chronic hepatitis B infection is safe and well tolerated and associated with durable virologic re- sponse with no detectable resistance: 8 year results from two phase 3 trials显示文摘 | Mmellin P Gane E Flisiak R | 2014 | Hepatology2014，60，： | 1 |
| 20 | Three-Year Efficacy and Safety of Tenofovir Disoproxil Fumarate Treatment for Chronic Hepatitis B显示文摘 | E. Jenny Heathcote Patrick Marcellin Maria Buti Edward Gane Robert A. De Man Zahary Krastev George Germanidis Samuel S. Lee Robert Flisiak Kelly Kaita Michael Manns Iskren Kotzev Konstantin Tchernev Peter Buggisch Frank Weilert Oya Ovunc Kurdas Mitchell L | 2011 | Gastroenterology2011，，1： | 1 |
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