Clinical course of primary sclerosing cholangitis and concomitant ulcerative colitis - a preliminary report of retrospective study among patients from Southern Poland.

UNLABELLED: Both ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) are chronic and progressive diseases of uncertain etiology, that may affect one patient. Approximately 70% of PSC cases are also diagnosed with UC, whereas in the group of UC the prevalence of PSC is about 2-5%. The aim of the study was to compare clinical courses of PSC and UC in patients diagnosed with both diseases to those with the confirmed diagnosis of either PSC or UC. Three groups were distinguished and evaluated: patients with PSC and UC (n = 17) and two control groups: patients with PSC (n = 4) and with UC (n = 13). Clinical data, symptoms, laboratory tests, results of the magnetic resonance cholangiopancreatography and colonoscopy were analyzed to compare clinical courses of these diseases between the groups. CONCLUSION: there is no correlation between clinical course of simultaneous PSC and UC. However, it may differ depending on co-occurrence of the other disease.

Inflammatory bowel disease: epidemiology, pathology and risk factors for hypercoagulability.

Hypercoagulability observed in patients with inflammatory bowel diseases (IBD) may lead to thromboembolic events (TE), which affect the venous and arterial systems alike and are an important factor in patients' morbidity and mortality. The risk of TE in IBD patients has been demonstrated to be approximately three-fold higher as compared to the general population. The pathogenesis of thrombosis in IBD patients is multifactorial and not fully explained. The most commonly listed factors include genetic and immune abnormalities, disequilibrium between procoagulant and anticoagulant factors, although recently, the role of endothelial damage as an IBD-triggering factor is underlined. Several studies report that the levels of some coagulation enzymes, including fibrinogen, factors V, VII, VIII, active factor XI, tissue factor, prothrombin fragment 1 + 2 and the thrombin-antithrombin complex, are altered in IBD patients. It has been demonstrated that there is a significant decrease of tissue plasminogen activator level, a marked increase of plasminogen activator inhibitor type 1 and thrombin-activable fibrinolysis inhibitor, a significantly lower level of antithrombin III and tissue factor pathway inhibitor. IBD patients have been also observed to produce an increased amount of various anticoagulant antibodies. Hyperhomocysteinemia, which is a potential risk factor for TE was also observed in some IBD patients. Further studies are necessary to assess the role of coagulation abnormalities in IBD etiology and to determine indications for thromboprophylactic treatment in patients at high risk of developing TE.

Reduced plasma fibrin clot permeability and susceptibility to lysis in patients with inflammatory bowel disease: a novel prothrombotic mechanism.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk of thromboembolism. Its mechanism is still unclear. Altered fibrin clot properties have been reported in patients with thromboembolism and those with chronic inflammatory states. We investigated whether fibrin characteristics are abnormal in IBD. METHODS: Ex vivo plasma fibrin clot permeability (Ks), compaction, turbidity, and efficiency of fibrinolysis were assessed in 85 consecutive patients with IBD, including 47 with ulcerative colitis (UC) and 38 with Crohn's disease (CD), all with no history of thromboembolism. Forty-eight patients matched for age and sex served as controls. RESULTS: Compared with controls, patients with UC and CD had 29.5% and 35.7% lower Ks associated with 13.8% and 23.1% lower compaction, respectively (all P < 0.001). Patients with UC and CD had higher maximum clot absorbance (+8.9%, P = 0.008, and +15.2%, P < 0.0001, respectively), higher maximum D-dimer released from clots (D-D(max), +27.0%, P = 0.01, and +28.7%, P < 0.0001, respectively), and prolonged clot lysis time (+19.0%, P < 0.0001, and +25.5%, P < 0.0001, respectively). Lag phase was similar in both group of patients. D-D(max) was the only parameter that differed between patients in the UC and CD groups, being higher in CD (P = 0.04). The multiple linear regression model showed that in patients with UC, but not with CD, Ks, compaction, lysis time, and D-D(max) were all independently associated with disease activity. In patients with CD, Ks and lysis time were independently predicted by fibrinogen and C-reactive protein. CONCLUSIONS: Both UC and CD are characterized by formation of dense fibrin networks relatively resistant to lysis. Prothrombotic clot phenotype might represent a novel mechanism increasing thrombotic risk in IBD.

TNF-α and soluble forms of TNF receptors 1 and 2 in the serum of patients with Crohn's disease and ulcerative colitis.

INTRODUCTION: Soluble forms of tumor necrosis factor (TNF) membrane receptors 1 and 2 (sTNFR1 and sTNFR2) are present in body fluids. Their higher concentrations are observed in a number of diseases, including inflammatory bowel diseases (IBDs). sTNFR1 and sTNFR2 are capable of binding TNF-α, acting as an inhibitor that competes with a membrane receptor. The results of the available studies on sTNFR1 and sTNFR2 concentrations in IBDs and their association with disease activity are ambiguous. OBJECTIVES: The aim of the study was to assess sTNFR1 and sTNFR2 concentrations and their correlation with disease activity in patients with IBD. PATIENTS AND METHODS: Plasma levels of TNF-α, sTNFR1, and sTNFR2 were measured in 55 consecutive patients with ulcerative colitis (UC), 50 subjects with Crohn's disease (CD), and 41 healthy controls. We assessed the associations of those markers with other inflammatory markers, disease activity and location, type of treatment, and complications. RESULTS: Positive correlations were observed between CD activity and sTNFR1 and sTNFR2 levels (r = 0.42 for both, P <0.01) as well as between UC activity and sTNFR1 and sTNFR2 levels (r = 0.63, P <0.0001; r = 0.47, P <0.001; respectively). TNF-α levels correlated only with CD activity (r = 0.29, P <0.05). In patients with nonactive UC, higher sTNFR2 levels were observed compared with controls. In patients with CD, higher TNF-α and sTNFR2 levels were demonstrated in patients who developed complications. CONCLUSIONS: sTNFR1 and sTNFR2 are more sensitive inflammatory markers than TNF-α in the assessment of disease activity in patients with CD and UC. Higher sTNFR2 levels are observed in patients with CD and complications.

IL28B polymorphism as a predictor of antiviral response in chronic hepatitis C.

AIM: To evaluate the effect of single nucleotide polymorphisms of interleukin (IL)-28B, rs12979860 on progression and treatment response in chronic hepatitis C. METHODS: Patients (n = 64; 37 men, 27 women; mean age, 44 ± 12 years) with chronic hepatitis C, genotype 1, received treatment with peg-interferon plus ribavirin. Genotyping of rs12979860 was performed on peripheral blood DNA. Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment. Serum viral load, aminotransferase activity, and insulin level were measured. Insulin resistance index, body mass index, waist/hip ratio, percentage of body fat and fibrosis progression rate were calculated. Applied dose of interferon and ribavirin, platelet and neutrophil count and hemoglobin level were measured. RESULTS: A sustained virological response (SVR) was significantly associated with IL28B polymorphism (CC vs TT allele: odds ratio (OR), 25; CC vs CT allele: OR, 5.4), inflammation activity (G < 1 vs G > 1: OR, 3.9), fibrosis (F < 1 vs F > 1: OR, 5.9), platelet count (> 200 × 10(9)/L vs < 200 × 10(9)/L: OR, 4.7; OR in patients with genotype CT: 12.8), fatty liver (absence vs presence of steatosis: OR, 4.8), insulin resistance index (< 2.5 vs > 2.5: OR, 3.9), and baseline HCV viral load (< 10(6) IU/mL vs > 10(6) IU/mL: OR, 3.0). There was no association with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or percentage body fat. There was borderline significance (P = 0.064) of increased fibrosis in patients with the TT allele, and no differences in the insulin resistance index between groups of patients with CC, CT and TT alleles (P = 0.12). Spearman's rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively (P < 0.001). Significant differences were found in the insulin resistance index (P = 0.01) between patients with and without steatosis. Patients with the CT allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon (P = 0.07). CONCLUSION: IL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy. Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.

Anti-inflammatory and anticoagulant properties of the protein C system in inflammatory bowel disease.

INTRODUCTION: In patients with inflammatory bowel disease (IBD), disbalance between procoagulant, anticoagulant, and fibrinolytic factors has been shown. The hemostatic system is an indispensable component of the inflammatory process. Deficiencies in the protein C (PC) pathway components not only promote thrombosis, but also exacerbate inflammation. OBJECTIVES: The aim of the study was to assess the components of the PC system and their correlations with disease activity in patients with IBD. PATIENTS AND METHODS: The levels of PC, free protein S (PS), and soluble thrombomodulin (sTM) were measured in 55 consecutive patients with ulcerative colitis (UC), 50 patients with Crohn's disease (CD), and 41 healthy volunteers. Correlations between PC system components and disease activity, hemostatic variables, and inflammatory markers were assessed. RESULTS: sTM levels in patiens with UC were higher compared with controls (24.5 vs. 17.5 ng/ml; P = 0.0042). In patients with IBD, PC activity was higher and PS activity was lower compared with controls (P <0.001). Tumor necrosis factor α (TNF-α) levels were higher in patients with IBD, and interleukin 6 (IL-6) levels were higher only in patients with CD. In patients with UC, a positive correlation was observed between sTM and both PC and PS levels (r = 0.28 and r = 0.34, respectively, P <0.05). Only PC levels correlated with UC activity (r = 0.3, P <0.05). No correlations of TNF-α, IL-6, and C-reactive protein with PC, PS, and sTM levels were observed. CONCLUSIONS: The PC pathway is defective in patients with CD and UC. Hypercoagulability in IBD might be associated not only with the inflammatory process but also with disturbances in the anticoagulant system, since defective PC pathway was observed both in active and nonactive disease.