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Effect of interferon alpha2b plus ribavirin treatment on selected growth factors in respect to inflammation and fibrosis in chronic hepatitis C

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World Journal of Gastroenterology 2005年第12期11卷 1854-1858页

作者： Panasiuk Anatol Flisiak Robert prokopowicz danuta Department of Infectious Diseases

AIM: Growth factors (GF) that participate in regeneration and apoptosis have an important role in chronic liver diseases. We analyzed serum GF concentration during antiviral treatment and correlated it with morphological liver failure in chronic hepatitis C. METHODS: The levels of GF were determined in sera by ELISA method in 0,16,32 and 48 wk of therapy in 40 patients treated with IFNα2b (9 MU sc/wk) and RBV (1.2 g/d) and in 25 healthy subjects. Blind liver biopsies were done before treatment with histological grading and staging examination. RESULTS: The hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were markedly elevated prior the treatment and decreased during the therapy, although they did not reach the normal level. In non-responding (NR) patients, HGF and EGF were higher than that in responders (R), however differences were not significant. Before the treatment thrombopoietin (TPO) level was significantly lower in R than in NR (P<0.03). Platelet-derived growth factor (PDGF) concentration was lower in chronic hepatitis C than in healthy subjects and decreased during the treatment. A significant positive correlation was observed between inflammatory activity in the liver tissue and the concentration of HGF (in R: r= 0.4, in NR: r= 0.5), TPO (R: r= 0.6), and a significant negative correlation between this activity and EGF (R: r = -0.6) and PDGF (R: r= -0.5). Serum HGF concentration was higher in more advanced fibrosis (R: r = 0.5, P<0.05; NR: r=0.4, P<0,03). CONCLUSION: The decrease in PDGF can be an effective prognostic marker of the treatment and HCV elimination. Decreasing HGF, EGF, and PDGF can influence the inhibition of inflammatory and fibrotic processes in the liver during the antiviral treatment.

关键词： Growth factor Chronic hepatitis C Liver biopsy Interferon alfa 2b Ribivirin

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Expression of p53,Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2006年第38期12卷 6198-6202页

作者： Anatol Panasiuk Janusz Dzieciol Bozena Panasiuk danuta prokopowicz Department of Infectious Diseases Medical University of Biaystok Poland Department of Human Anatomy Medical University of Bialystok Poland

AIM: To analyze the protein expression essential for apoptosis in liver steatosis. METHODS: The expression of proapoptotic proteins p53, Bax, and antiapoptotic Bcl-2 in hepatocytes with steatosis (SH) and without steatosis (NSH) was evaluated in 84 patients at various stages of non-alcoholic fatty liver disease (NAFLD). RESULTS: Immunohistochemical staining of liver tissue showed the activation of p53 protein in SH and NSH with increased liver steatosis, diminished Bcl-2 and slightly decreased Bax protein. Positive correlation was found between the stage of liver steatosis with p53 expression in SH (r = 0.54, P < 0.01) and NSH (r = 0.49, P < 0.01). The antiapoptotic protein Bcl-2 was diminished together with the advancement of liver steatosis, especially in non-steatosed hepatocytes (r =0.43, P < 001). CONCLUSION: Apoptosis is one of the most important mechanisms leading to hepatocyte elimination in NAFLD. The intensification of inflammation in NAFLD induces proapoptotic protein p53 with the inhibition of antiapoptotic Bcl-2.

关键词： Apoptosis Non-alcoholic liver disease p53 Bcl-2 Bax Immunohistochemistry

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Expression of bcl-2 protein in chronic hepatitis C:Effect of interferon alpha 2b with ribavirin therapy

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World Journal of Gastroenterology 2005年第19期11卷 2949-2952页

作者： Panasiuk Anatol prokopowicz danuta Dzieciol Janusz Panasiuk Bozena Department of Infectious Diseases Medical University of Bialystok Zurawia Str.1415-540 BialystokPoland Department of Human Anatomy Medical University of Bialystok Zurawia Str.1415-540 BialystokPoland

AIM: Mechanisms responsible for persistence of HCV infection and liver damage in chronic hepatitis C are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic protein bcl-2 expression on liver tissue as well as the influence of interferon alpha 2b (IFNa2b) and ribavirin (RBV) were analyzed in patients with chronic hepatitis C. METHODS: In 30 patients with chronic hepatitis C (responders - R and non-responders - NR) treated with IFNα2b+RBV, protein bcl-2 was determined in hepatocytes and in liver associated lymphocytes before and after the treatment. RESULTS: The treatment diminished bcl-2 protein accumulation in liver cells in_patients with hepatitis C (P<0.05). Before and after the therapy, we detected bcl-2 protein in R in 87±15% and 83±20% of hepatocytes and in 28±18% and 26±10% of liver-associated lymphocytes, respectively. In NR, the values before treatment decreased from 94±32% to 88±21% of hepatocytes and 39±29% to 28±12% of lymphocytes with bcl-2 expression. There was no statistical correlation between bcl-2 expression on liver tissue with inflammatory activity, fibrosis and biochemical parameters before and after the treatment. CONCLUSION: IFNα2b+RBV treatment, by bcl-2 protein expression decrease, enables apoptosis of hepatocytes and associated liver lymphocytes, which in turn eliminate hepatitis C viruses.

关键词： Bcl-2 Chronic hepatitis C Interferon alpha Ribavirin Hepatitis C virus

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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

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Four-year follow up of hepatitis C patients vaccinated against hepatitis B virus

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World Journal of Gastroenterology 2005年第12期11卷 1798-1801页

作者： Slawomir Chlabicz Tadeusz Wojciech Lapinski Anna Grzeszczuk danuta prokopowicz Department of Family Medicine and Community Nursing Department of Infectious Diseases

AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis ***: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization ***: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P＜0.05).Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P＜0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc ***: We demonstrated that 4 years after HBV immunizations' more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provideprotection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.

关键词： Hepatitis B Hepatitic C vaccine Follw-up studies

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Serum concentration of sFas and sFasL in healthy HBsAg carriers,chronic viral hepatitis B and C patients

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World Journal of Gastroenterology 2004年第24期10卷 3650-3653页

作者： Tadeusz Wojciech Lapinski Oksana Kowalczuk danuta prokopowicz Lech Chyczewski Department of Infectious Diseases Medical University of BialystokPoland Institute of Molecular Biology Medical University of BialystokPoland

AIM:To estimate the amount of apoptosis among healthy HBsAg carriers,patients with chronic HBV infection treated wibh lamivudine and patients with chronic HCV infection treated with interferon alpha and *** of apoptosis was evaluated by serum sFas/sFasL concentration measurement. Moreover dependence between apoptosis and HBV-DNA or HCV-RNA levels was studied. METHODS:Eighty-six persons were included into study:34 healthy HBsAg carders,33 patients with chronic HBV infecl^on and 19 patients with chronic HCV *** levels of sFas/sFasL were measured by ELISA ***-DNA and HCV-RNA were measured by RT-PCR *** of sFas/sFasL were determined before and 2 and 12 wk after therapy in patients with chronic hepatitis B and C infection. HBV-DNA or HCV-RNA was detected before treatment and 6 mo after treatment. RESULTS:Twenty-four (71%) healthy HBsAg carders showed HBV-DNA over 10~5/mL,which was comparable to the patients with chronic hepatitis *** from HBV-DNA levels, the concentration of sFas among healthy HBsAg carders was comparable to healthy *** patients with chronic hepatitis B and C,the concentration of sFas was significantly higher in comparison to healthy HBsAg carriers and healthy *** chronic hepatitis B patients the concentration of sFas was decreased during lamivudine *** chronic hepatitis C patients the concentration of sFas was increased during IFN alpha and ribavirin treatment,sFasL was not detected in control *** sFasL occurred more frequently in chronic hepatitis C patients in comparison to chronic hepatitis B patients. CONCLUSION:There are no correlations between apoptosis and HBV-DNA *** ther is an association between apoptosis and activity of inflammation in patients with chronic HBV *** can be increased in patients with chronic hepatitis C by effective treatment which may be a result of apoptosis stimulation by IFN-α.

关键词： Adolescent Adult Aged Antigens, CD95 Apoptosis Biological Markers Carrier State DNA, Viral Female Hepatitis B Surface Antigens Hepatitis B, Chronic Hepatitis C, Chronic Humans Lamivudine Male Membrane Glycoproteins Middle Aged RNA, Viral Reverse Transcriptase Inhibitors Solubility

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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

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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

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Expression of β2-integrin on leukocytes in liver cirrhosis

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World Journal of Gastroenterology 2006年第38期12卷 6193-6197页

作者： Anatol Panasiuk Janusz ■ak Elzbieta Maciorkowska Bozena Panasiuk danuta prokopowicz Department of Infectious Diseases Medical University of Bialystok Poland Department of Pediatrics Diagnostics Medical University of Bialystok Poland Department of Pediatric Nursing Medical University of Bialystok Poland

AIM： To analyze β2-integrin expression on blood leukocytes in liver drrhosis.METHODS： In 40 patients with liver cirrhosis and 20 healthy individuals, the evaluation of expression of CD11a （LFA-1α）, CD11b （Mac-1α）, CD11c （αX） and CD49d （VLA-4α） on peripheral blood leukocytes was performed using flow cytometry. The analysis was carried out in groups of patients divided into B and C according to Child-Pugh＇s classification. RESULTS： An increased CDlla, CD11b, CD11c and CD49d integrin expression was observed on peripheral blood leukocytes in liver cirrhosis. The integrin levels were elevated as the advancement of liver failure progressed. The highest expression of integrins occurred predominantly on monocytes. A slight expression of VLA-4 was found on lymphocytes and granulocytes and it increased together with liver failure. A positive correlation was noted between median intensity of fluorescence （MIF） expression on polymorphonuclear cells of CD11a and CD11c and CD49d （r = 0.42, P 〈 0.01; r = 053, P 〈 0.01, respectively） in liver cirrhosis stage C. However, no correlation was observed between integrin expression on leukocytes. The concentrations of sICAM-1, sVCAM-1, and TNFα, were significantly elevated in liver cirrhosis. CONCLUSION： β2-integrin expression on leukocytes increases in liver cirrhosis decornpensated as the stage of liver failure increases, which is a result of permanent activation of leukooytes circulating through the inflamed liver environment.β2-integrin expression on circulating leukocytes can intensify liver cirrhosis,

关键词： β2-integrin Liver cirrhosis Flow cytometry Leukocytes

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High concentration of antimitochondrial antibodies predicts progressive primary biliary cirrhosis

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World Journal of Gastroenterology 2005年第36期11卷 5706-5709页

作者： Robert Flisiak Maria Pelszynska danuta prokopowicz Magdalena Rogalska Urszula Grygoruk Department of Infectious Diseases Medical University of Bialystok Poland

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 3 patients 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. 2005 The WJG Press and Elsevier Inc. All rights reserved.

关键词： Primary biliary cirrhosis Autoantibodies Liver

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