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Successful antiviral therapy is associated with a decrease of serum prohepcidin in chronic hepatitis C

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World Journal of Gastroenterology 2010年第14期16卷 1747-1752页

作者： jerzy jaroszewicz Magdalena Rogalska Iwona Flisiak Robert Flisiak Department of Infectious Diseases and Hepatology Medical University of Bialystok Bialystok 15-540 Poland Department of Dermatology and Venereology Medical University of Bialystok Bialystok 15-540 Poland

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.

关键词： Iron metabolism Hepcidin Hepatitis C virus Interferon Sustained viral response

Epidemiological characteristics of inflammatory bowel disease in North-Eastern Poland

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World Journal of Gastroenterology 2005年第17期11卷 2630-2633页

作者： Alicja Wiercinska-Drapalo jerzy jaroszewicz Robert Flisiak Danuta Prokopowicz Department of Infectious Diseases Intestinal Diseases Unit Medical University of Bialystok15-540 BialystokZurawia str. 14Poland

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.

关键词： IBDepidemiology Extraintestinal manifestations Employment discontinuation

Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity

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World Journal of Gastroenterology 2003年第12期9卷 2843-2845页

作者： Alicja Wiercinska-Drapalo jerzy jaroszewicz Robert Flisiak Danuta Prokopowicz Department of Infectious Diseases Intestinal Diseases UnitMedical University of BialystokPoland

AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel *** 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 *** was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease ***: 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.

关键词： Adult Aged Biological Markers C-Reactive Protein Colitis, Ulcerative Comparative Study Female Humans Interstitial Collagenase Male Middle Aged Reference Values Tissue Inhibitor of Metalloproteinase-1

Plasma interleukin-18 reflects severity of ulcerative colitis

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World Journal of Gastroenterology 2005年第4期11卷 605-608页

作者： Alicja Wiercinska-Drapalo Flobert Flisiak jerzy jaroszewicz Danuta Prokopowicz Department of Infectious Diseases Intestinal Diseases Unit Medical University of BialystokZurawia str. 1415-540 Biaystok Poland

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.

关键词： Ulcerative colitis Interleukin-18

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

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World Journal of Gastroenterology 2005年第43期11卷 6833-6838页

作者： Robert Flisiak jerzy jaroszewicz Tadeusz W Lapiski Iwona Flisiak Danuta Prokopowiczi Department of Infectious Diseases Department of Dermatology and Venereology

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 low MMP-1 plasma concentratio

关键词： HCV Hepatitis Liver Interferons Fibrosis

Specific ssDNA concentration in liver tissue as an index of apoptosis in hepatitis C virus-infected patients

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World Journal of Gastroenterology 2005年第39期11卷 6130-6133页

作者： Tadeusz Wojciech Lapiski Anatol Panasiuk jerzy jaroszewicz Oksana Kowalczuk Robert Flisiak Magdalena Rogalska Department of Infectious Diseases Medical University of Bialystok Poland Department of Infectious Diseases Medical University of BialystokPolandDepartment of Infectious Diseases Medical University of BialystokPolandInstitute of Molecular Biology Medical University of BialystokPolandDepartment of Infectious Diseases Medical University of BialystokPolandDepartment of Infectious Diseases Medical University of BialystokPoland

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.

关键词： Apoptosis Hepatitis C virus ssDNA Fibrosis

Efficiency and safety of lamivudine therapy in patients with chronic HBV infection, dialysis or after kidney transplantation

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World Journal of Gastroenterology 2005年第3期11卷 400-402页

作者： Tadeusz Wojciech Lapinski Robert Flisiak jerzy jaroszewicz Ma3gorzata Michalewicz Oksana Kowalczuk Department of Infectious Diseases Institute of Molecular Biology

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

关键词： Chronic HBV infection Lamivudine Kidney transplantation Hemodialysis

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

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World Journal of Gastroenterology 2004年第18期10卷 2661-2665页

作者： Robert Flisiak Haza Al-Kadasi jerzy jaroszewicz Danuta Prokopowicz Iwona Flisiak Department of Infectious Diseases Medical UniversityBialystokPoland Department of Dermatology and Venereology Medical UniversityBialystokPoland

AIM: Transforming growth factor (TGF)-β1, metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP)-I are considered predictive biomarkers of chronic hepatitis activity and *** aim of this study was to evaluate the effect of lamivudine treatment on the plasma levels of these peptides in patients with chronic hepatitis ***: 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 ***: 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 ***: These findings support the role of TGF-β1,TIMP-1 and MMP-1 in the pathogenesis of chronic hepatitis *** of their association with hepatic injury and antiviral treatment efficacy, determination of these peptides may be useful in disease management.

关键词：血浆转化生长因素β1 TGF-β1 组织抑制剂金属蛋白质-1 慢性乙型肝炎 HBV 抗原

Best therapy for the easiest to treat hepatitis C virus genotype 1binfected patients

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World Journal of Gastroenterology 2022年第45期28卷 6380-6396页

作者： Dorota Zarębska-Michaluk Michal Brzdęk jerzy jaroszewicz Magdalena Tudrujek-Zdunek Beata Lorenc Jakub Klapaczyński Włodzimierz Mazur Adam Kazek Marek Sitko Hanna Berak Justyna Janocha-Litwin Dorota Dybowska Łukasz Supronowicz Rafal Krygier Jolanta Citko Anna Piekarska Robert Flisiak Department of Infectious Diseases Jan Kochanowski UniversityKielce 25-317Poland Department of Infectious Diseases and Hepatology Medical University of SilesiaKatowice 40-055Poland Department of Infectious Diseases Medical University of LublinLublin 20-059Poland Pomeranian Center of Infectious Diseases Medical University GdańskGdańsk 80-214Poland Department of Internal Medicine and Hepatology Central Clinical Hospital of the Ministry of Internal Affairs and AdministrationWarszawa 00-241Poland Clinical Department of Infectious Diseases Medical University of SilesiaChorzów 41-500Poland ID Clinic Mysłowice 41-400Poland Department of Infectious and Tropical Diseases Jagiellonian UniversityKraków 31-088Poland Hospital for Infectious Diseases Hospital for Infectious DiseasesWarszawa 02-091Poland Department of Infectious Diseases and Hepatology Medical University WrocławWrocław 50-367Poland Department of Infectious Diseases and Hepatology Faculty of MedicineNicolaus Copernicus UniversityBydgoszcz 85-030Poland Department of Infectious Diseases and Hepatology Medical University of BiałystokBiałystok 15-089Poland Infectious Diseases and Hepatology Outpatient Clinic Gemini NZOZŻychlin 62-571Poland Medical Practice of Infections Regional HospitalOlsztyn 10-561Poland Department of Infectious Diseases and Hepatology Medical UniversityŁódźŁódź90-419Poland

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 *** To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological *** This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 *** 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 *** 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 *** effectiveness of all regimens exceeded 90%and the highest SVR of 98.9%was achieved in patients treated with a combination of glecaprevir/*** 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

关键词： Hepatitis C Genotype 1b Direct-acting antivirals Pangenotypic Genotype-specific Sustained virologic response