Portal pressure predicts outcome and safety of antiviral therapy in cirrhotic patients with hepatitis C virus infection.

BACKGROUND & AIMS: There are limited data on the efficacy and safety of antiviral therapy in patients with hepatitis C virus (HCV)-related cirrhosis, particularly on the impact of portal hypertension. METHODS: We assessed hepatovenous pressure gradient (HVPG), liver stiffness (transient elastography), and interleukin (IL)-28B polymorphisms (rs12979860) in 90 cirrhotic patients with HCV infection (82% genotype 1 or 4) before antiviral therapy with pegylated interferon and ribavirin. Efficacy and safety were evaluated. RESULTS: Rates of sustained virologic response were significantly lower among patients with clinically significant portal hypertension (CSPH; HVPG ≥ 10 mm Hg; n = 50) than among patients without CSPH (HVPG <10 mm Hg; n = 40): 14% vs 51% (P = .0007). Seventy-nine percent and 83% of patients with CSPH and without CSPH, respectively, received more than 80% of planned dose (P = .647). The predictive value of HVPG (area under the curve [AUC], 0.743) was greater than that of liver stiffness (AUC, 0.647) or of baseline HCV RNA levels (AUC, 0.620). The IL-28B polymorphism was not associated significantly with a sustained virologic response. Multivariate analysis revealed that HVPG (odds ratio [OR], 14.3; P = .009), baseline HCV RNA levels (OR, 5.3; P = .019), and HCV genotype (OR, 6.5; P = .046) were independent risk factors for treatment failure. A trend toward higher incidence of anemia and neutropenia was observed for patients with CSPH. The incidence and grade of thrombocytopenia were significantly higher among patients with than without CSPH (94% vs 75%; P = .006). CONCLUSIONS: HVPG is an independent predictor of response to antiviral therapy, with better predictive value than liver stiffness, baseline HCV RNA levels, HCV genotype, or IL-28B polymorphism. The incidence and grade of thrombocytopenia during antiviral therapy are higher among patients with CSPH. In evaluating cirrhotic HCV patients for antiviral treatment, measurement of HVPG should be considered.

Mitochondrial toxicity is associated with virological response in patients with HIV and hepatitis C virus coinfection treated with ribavirin and highly active antiretroviral therapy.

The combination of highly active antiretroviral therapy (HAART) plus ribavirin (RBV) in patients with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection has been reported to cause mitochondrial toxicity (MT). Sixty-four patients with HIV-HCV coinfection who were receiving antiviral therapy were evaluated for MT. Patients with concomitant HAART showed greater increases in lactate levels than did patients without HAART, and this difference was more pronounced in patients who received higher dosages of RBV. The incidence of pancreatic enzyme elevations and symptomatic pancreatitis was higher among patients who received HAART and high-dose RBV. Hepatic steatosis increased in patients who received HAART and high-dose RBV. Patients who showed signs of MT achieved higher rates of sustained virologic response than did patients without MT (73% vs 44%).

A double-blind, randomized, placebo-controlled trial of intravenous L-ornithine-L-aspartate on postural control in patients with cirrhosis.

INTRODUCTION: Hepatic encephalopathy (HE) is a complication of liver disease. Several treatments have been introduced but only L-ornithine-L-aspartate (LOLA) shows proven efficacy. This double-blind, randomized, placebo-controlled trial evaluated the effect of LOLA on postural control in cirrhotics. METHODS: Forty patients were randomized to either LOLA or a placebo. HE was evaluated by psychometric testing (PSE Syndrome Test) and critical flicker frequency (CFF). Posturography [equilibrium score (ES)] provided information regarding postural control. Peripheral blood was analysed for ammonia concentration (NH(3)) and the partial pressure of ammonia (pNH(3)). RESULTS: Both groups were comparable regarding baseline variables. Posturography and PSE Syndrome Test improved in both groups; improvement was greater in the LOLA group (ES: 5.3%; PSE: 1.9) compared with the placebo (ES: 3.9%; PSE: 1.3) but did not reach significance (ES: P=0.3; PSE: P=0.5). CFF remained unchanged during treatment and between groups (P=NS). NH(3) decreased in the LOLA group (Delta: -15 micromol/L) and slightly increased in the placebo group (Delta: 11.1 micromol/L), but the differences did not reach statistical significance (P=0.07). pNH(3) remained largely unchanged (LOLA Delta: -1.2 x 10(-5) mmHg vs. placebo Delta: -0.3 x 10(-5) mmHg; P=0.21). CONCLUSION: In the LOLA group, an improvement of posturographic control and PSE Syndrome Test was observed, but a similar improvement was also achieved by the placebo. In LOLA, ammonia levels tended to decrease while they tended to increase in the placebo group. LOLA might augment the improvement achieved by intravenous fluids alone but a larger cohort will be needed to show this effect with statistical significance.

Sorafenib attenuates the portal hypertensive syndrome in partial portal vein ligated rats.

BACKGROUND/AIMS: Angiogenesis plays a key role in development of portal hypertension (PHT) and represents a potential therapeutic target. We aimed to evaluate the molecular effects of sorafenib, a multiple tyrosine kinase inhibitor, on splanchnic hemodynamics in rats with partial portal vein ligation (PPVL). METHODS: The following four groups of rats were treated orally with sorafenib (10mg/kg per day; SORA group) or placebo (PLAC group) for 7 days, beginning at the day of PPVL or sham operation (SO): (1) PPVL-SORA, (2) PPVL-PLAC, (3) SO-SORA and (4) SO-PLAC. Measurements of mean arterial pressure (MAP), portal pressure (PP), and superior mesenterial artery blood flow (SMABF) were performed. Portosystemic collateral blood flow (PSCBF) was determined by radioactive microspheres. Splanchnic protein expression of CD31, alpha-smooth muscle actin (alphaSMA), phospho-extracellular signal-regulated kinase (pERK), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), tumor necrosis factor alpha (TNFalpha), and endothelial nitric oxide synthetase (eNOS) was assessed by Western blot. Gene expression was studied by angiogenesis-focused real-time reverse transcription polymerase chain reaction microarray. RESULTS: PP, SMABF, and PSCBF were significantly higher in PPVL rats than in SO rats. MAP and heart rate were similar in all groups. Treatment with sorafenib resulted in a significant decrease of PP (p<0.001) and SMABF (p<0.05) in PPVL-SORA rats compared to PPVL-PLAC rats. PPVL-SORA rats had markedly less PSCBF than PPVL-PLAC rats (p<0.001). Superior mesenteric artery resistance (SMAR) was significantly lower in both PPVL groups compared to both SO groups, but PPVL-SORA rats showed significantly higher SMAR than PPVL-PLAC rats (p<0.05). The increased protein expression of CD31, alphaSMA, pERK, VEGF, PDGF, TNFalpha, and eNOS in rats with PHT was markedly decreased by sorafenib treatment. Sorafenib decreased mRNA levels of TNFalpha, VEGF receptor 2, VEGF receptor 1, transforming growth factor beta, cyclooxygenase 1, and expression of various genes that are involved in pathways of cellular proliferation, fibrogenesis, tissue remodeling, inflammation, and angiogenesis. CONCLUSIONS: Treatment with sorafenib reduced PP, SMABF, and PSCBF in noncirrhotic rats with prehepatic PHT, without affecting systemic hemodynamics. Additional antiproliferative, anti-inflammatory, and antiangiogenic effects of sorafenib were identified.

IP-10 correlates with hepatitis C viral load, hepatic inflammation and fibrosis and predicts hepatitis C virus relapse or non-response in HIV-HCV coinfection.

BACKGROUND: Interferon (IFN)-gamma inducible protein 10 (IP-10) is increased in hepatitis C virus (HCV) monoinfection, correlates with hepatic inflammation and predicts non-response (NR) to antiviral therapy. We aimed to clarify the role of IP-10 in HIV-HCV coinfection. METHODS: Serum IP-10 levels of 30 HIV-HCV-coinfected patients treated with pegylated (PEG)-IFN-alpha2a (180 microg/week) and ribavirin (800-1,200 mg/day) were measured at baseline and 24 h after first IFN dose. The predictive value of IP-10 was compared with established markers of treatment outcome by applying a multivariate logistic regression model. RESULTS: Patients with NR (476 +/- 156 pg/ml) or virological relapse (508 +/- 298 pg/ml) had significantly higher baseline IP-10 levels compared with patients who had a sustained virological response (SVR; 293 +/- 97 pg/ml, P = 0.001). The IFN-induced increase of IP-10 was significantly stronger in patients with an SVR (P = 0.017). IP-10 levels were associated with HCV viral load, alanine aminotransferase (ALT) levels, hepatic inflammatory activity and fibrosis stage. Advanced fibrosis, high HCV viral load, hepatovenous pressure gradient and pretreatment IP-10 > 400 pg/ml predicted NR to antiviral therapy. In the multivariate analysis, IP-10 was identified as the strongest baseline predictor of SVR with a specificity and sensitivity of 83.4% and 92.9%, respectively. CONCLUSIONS: Pretreatment IP-10 levels correlated with HCV viral load, ALT levels, hepatic inflammation and fibrosis. An IP-10 cutoff level of 400 pg/ml might serve as a useful predictive marker for anti-HCV therapy in HIV-HCV-coinfected patients because it could discriminate patients with expected NR or HCV relapse after therapy from patients with an SVR before starting antiviral treatment.

Impact of interobserver disagreement on phenotype-genotype associations in Crohn's disease.

BACKGROUND: Nonvalidated definitions of disease-related parameters in inflammatory bowel disease cause variations in diagnosis and disease classification. We determined interobserver agreement on applications of definitions of the Vienna Classification variables and computed the potential influence of misclassification on genotype/phenotype associations. METHODS: Ten records of patients with Crohn's disease (CD) were independently evaluated by 19 observers using a standardized inflammatory bowel disease documentation system, which included the Vienna Classification. Interobserver agreement (IOA) was calculated as a percentage of the observers' agreement with a predetermined reference observer and by Cohen's kappa. Randomized reclassifications were then computed with 10,000 simulation runs using the IOA results and published NOD2/CARD15 gene status. A chi-square independence test was calculated for each simulation run. RESULTS: IOA for location and behavior was 70% (K = 0.57) and 95% (K = 0.91), respectively. IOA for location subgroups ranged from 48% to 88% and for behavior from 91% to 97%. By including the results of histopathology into the evaluation of location, the overall IOA increased significantly, to 80% (P = 0.019). Assuming a true genotype/phenotype association, the proportion of studies with nonsignificant findings (P > 0.05) because of the observed misclassification of location ranged from 13.3% to 63.8% and of behavior from 0.2% to 22.2%, depending on a study sample size of 500 or 150 patients respectively. CONCLUSIONS: We concluded that there is appreciable interobserver disagreement on the location of CD according to the original Vienna Classification that may obscure true genotype/phenotype associations. Definitions of disease parameters have to be validated before being used as the bases for classifications.

Antiviral therapy decreases GpIIb/IIIa activation of platelets in patients with chronic hepatitis C.

Interferon alpha (IFN-alpha) is used to treat haematological and solid malignancies and is the gold standard therapy for chronic hepatitis C infection in combination with ribavirin. It has a well known platelet lowering effect and was recently shown to impair platelet aggregation in the presence of various agonists and has been accused to increase patients' bleeding risk during IFN-alpha therapy. Thus, we hypothesised that antiviral treatment decreases GpIIb/IIIa activation and affects global platelet function. In a prospective clinical trial, we examined the effects of combination therapy with pegylated IFN-alpha 2a (PegIFN-alpha 2a) and ribavirin on platelet GpIIb/IIIa activation and platelet secretion in 20 patients with chronic hepatitis C at week 2, 4, 8 and 12 after the beginning of therapy. In addition, we determined global platelet function (CEPI-CT) with the PFA-100 and vWF-Ag levels. Antiviral therapy significantly decreased GpIIb/IIIa activation in a time dependent manner, whereas markers of platelet secretion (P-selectin, beta-thromboglobulin) remained unchanged. Despite a marked elevation of vWF-Ag levels, CEPI-CT did not change compared to baseline levels. Antiviral therapy significantly decreases GpIIb/IIIa activation in patients with chronic hepatitis C, while vWG-Antigen levels are markedly increased and alpha-granule secretion is not affected. This does not result in an alteration of global platelet function as assessed by the PFA-100, because elevated vWF-Antigen levels might compensate for the acquired defect.

Resistance to activated protein C is a risk factor for fibrostenosis in Crohn's disease.

AIM: To evaluate the effect of resistance to activated protein C (aPCR), the most common known inherited thrombophilic disorder, on the risk of intestinal operation of fibrostenosis in patients with Crohn's disease (CD). METHODS: In a previous study, we assessed the prevalence of aPCR in CD. In a retrospective case-controlled study, 8 of these CD patients with aPCR were now compared with 24 CD patients without aPCR, matched by gender, age at diagnosis and duration of disease in a 1:3 fashion. The primary end point was the occurrence of an intestinal CD-related operation with evidence of fibrostenosis in the bowel resection specimen. RESULTS: The Kaplan-Meier analysis revealed that patients with aPCR had a lower probability of remaining free of operation with fibrostenosis than patients without aPCR (P = 0.0372; exact log-rank test) resulting in a significantly shorter median time interval from diagnosis of CD to the first operation with fibrostenosis (32 vs 160 mo). At 10 years, the likelihood of remaining free of operation with fibrostenosis was 25% for patients with aPCR and 57.8% for patients without aPCR. CONCLUSION: CD patients with aPCR are at higher risk to undergo intestinal operation of fibrostenosis than those without aPCR. This supports our hypothesis of aPCR being a possible risk factor for fibrostenosis in CD.

Assessing the demand for psychological care in chronic diseases: development and validation of a questionnaire based on the example of inflammatory bowel disease.

BACKGROUND: This study was designed to develop and validate the ADAPT (Assessment of the Demand for Additional Psychological Treatment), a questionnaire assessing the demand for disease-oriented counseling (DOC), integrated psychosomatic care (IPC), and psychotherapy (PT) in chronically ill patients on the example of inflammatory bowel diseases (IBDs). METHODS: After its development, the ADAPT was distributed to 39 IBD patients along with the Hospital Anxiety and Depression scale (HAD), the Rating Form of IBD Patient Concerns (RFIPC), and a questionnaire on social support (SOZU-K22). For construct validity, 19 hypotheses were made on how DOC, IPC, and PT should correlate with HAD, RFIPC, SOZU-K22, and disease-related variables. To analyze interindividual responsiveness, patients were classified according to their bio-psycho-social state, and DOC, IPC, and PT scores were compared between these classes. The test-retest method with a 4-week time lapse was used to analyze reliability and intraindividual responsiveness. DOC, IPC, and PT scores between baseline and follow-up were compared separately for patients classified as "stable" or "changed" according to changes in HAD and disease activity. RESULTS: Observed correlations were largely in agreement with the 19 hypotheses. DOC, IPC, and PT achieved significantly different scores between different patients. After 4 weeks, DOC, IPC, and PT revealed stable scores in patients with "stable" HAD and revealed significantly different scores in patients with "changed" HAD. Changed disease activity was not associated with significant changes of the ADAPT. CONCLUSIONS: The ADAPT is the first questionnaire to assess subjective demand for additional psychological care in chronically ill patients. The first application of the ADAPT to 39 IBD patients suggests its validity, reliability, and responsiveness.

Impact of depressive mood on relapse in patients with inflammatory bowel disease: a prospective 18-month follow-up study.

OBJECTIVE: There is evidence of an interaction between psychological factors and activity of inflammatory bowel disease (IBD). We examined the influence of depressive mood and associated anxiety on the course of IBD over a period of 18 months in a cohort of patients after an episode of active disease. METHODS: In this prospective, longitudinal, observational study, 60 patients (37 women and 23 men) with clinically inactive IBD (Crohn disease, n = 47, 78%; ulcerative colitis, n = 13, 22%) were enrolled after a flare of disease. Psychological status, health-related quality of life (HRQOL), and disease activity were evaluated at baseline and then every 3 months for a period of 18 months by means of clinical and biological parameters, the Beck Depression Inventory (BDI), the Spielberger State-Trait Anxiety Inventory, the Inflammatory Bowel Disease Questionnaire, the Perceived Stress Questionnaire, and the Rating Form of Inflammatory Bowel Disease Patients Concerns. RESULTS: At baseline, depression (BDI > or = 13 points) was found in 17 of 60 (28%) patients. Thirty-two patients (59%) experienced at least one relapse during the 18 months of follow-up. Regression analysis showed a significant correlation between BDI scores at baseline and the total number of relapses after 12 (p <.01) and 18 months (p <.01) of follow-up. Furthermore, depression scores at baseline correlated with the time until the first recurrence of the disease (p <.05). Anxiety and low HRQOL were also related with more frequent relapses during follow-up (p <.05 and p <.01, respectively). CONCLUSIONS: Psychological factors such as a depressive mood associated with anxiety and impaired HRQOL may exert a negative influence on the course of IBD. Therefore, assessment and management of psychological distress should be included in clinical treatment of patients with IBD.

Chemoembolization with cisplatin, lipiodol and Gelfoam and subsequent systemic chemotherapy with cisplatin and interferon in patients with hepatocellular carcinoma: a non-randomized prospective study.

Arterial chemoembolization with subsequent systemic chemotherapy was assessed prospectively. Of 94 consecutive patients with HCC, 31 patients were considered to have inoperable disease and were selected for chemoembolization. Twenty-two of the 31 patients underwent chemoembolization. In eight patients, technical problems with catheterization prevented the application of therapy, and one patient rejected further treatment. Regimen: Three monthly cycles of chemoembolization with cisplatin 20 mg/m(2) mixed with lipiodol delivered intraarterially with Gelfoam or collagen on day 1, followed by intravenous chemotherapy with cisplatin 60 mg/m(2) on day 2; interferon alpha-2c 30 microg (10 M IU) subcutaneously on days 2, 5, 9, and 12. Three percent of the patients (1/31) (CI 95% 0.08; 16.7) experienced a partial clinical response, in 53% alpha-fetoprotein levels decreased by more than 50%. On univariate analysis, performance status, Child score, Okuda stage, albumin levels, and lactate dehydrogenase were found to have an effect on survival. Postchemoembolization syndrome occurred in 68% of the patients, nausea/vomiting grades 3/4 (according to the World Health Organization WHO) in six patients, anemia grade 3 in three patients, leukopenia grade 3 in one patient and thrombocytopenia grade 3 in one patient. This treatment regimen is a very selective procedure. Because of the low response rate it is not recommended for routine clinical use.

Do high serum levels of anti-Saccharomyces cerevisiae antibodies result from a leakiness of the gut barrier in Crohn's disease?

OBJECTIVES: To examine the relationship between serum levels of anti-Saccharomyces cerevisiae antibodies (ASCAs) and intestinal permeability at a given time (hypothesis 1) and the probability of increased ASCA serum levels with increased intestinal permeability (hypothesis 2) in patients with Crohn's disease. METHODS: Each hypothesis was tested retrospectively with its own study population: group A for hypothesis 1 and group B for hypothesis 2. Intestinal permeability was measured by lactulose/mannitol test and ASCAs were quantified by using ELISA. Patients received either no treatment or 5-aminosalicylates. The lactulose/mannitol test and sampling of sera for ASCA assessment had to be performed within 1 month in group A. In group B the highest intestinal permeability value obtained from among at least three measurements made during different stages of disease activity was chosen for evaluation. RESULTS: Both study populations consisted of 140 patients with Crohn's disease. Elevated IgG ASCAs were detected in 64% (90/140) in group A compared with 65% (91/140) in group B. In group A, 64% (90/140) and in group B 66% (92/140) were IgA ASCA positive. Correlation analysis showed a tendency for a positive relationship between IgG ASCAs and intestinal permeability in group A (tau = 0.16, P = 0.07) and in group B (tau = 0.16, P = 0.06). A positive trend was seen for the combination of high intestinal permeability and high IgG ASCAs in group B (chi-squared test, P = 0.07). CONCLUSION: Elevated serum levels of anti-S. cerevisiae antibodies do not seem to result primarily from a defect of the gut barrier. This observation points to an intrinsic pathomechanism in the development of increased ASCA serum levels.

Heterogeneous expression and regulation of CD40 in human hepatocellular carcinoma.

OBJECTIVE: CD40, a member of the tumour necrosis factor receptor family, plays a major role in adaptive immune responses and contributes to cancer surveillance. Conflicting results have been reported recently on the expression and function of CD40 in carcinomas. The aim of the present study was to investigate the role of CD40 in human hepatoma. DESIGN/METHODS: CD40 expression was examined in hepatomas and derived cell lines by immunohistochemistry, flow cytometry and reverse transcriptase polymerase chain reaction. We investigated in hepatoma cell lines the regulation of CD40 by pro-inflammatory cytokines and the effects of its ligation with soluble CD40L on the expression of co-stimulatory and pro-apoptotic cell-surface molecules and survival. RESULTS: CD40 was detected with a similar frequency of about 40% in hepatoma specimens and derived cell lines but not in normal hepatocytes. Tumour necrosis factor alpha and its combination with interferon gamma upregulated CD40 only in intrinsically positive cell lines. CD40 ligation had no effect on cell viability or surface expression of CD54, CD80, CD86 or CD95. CONCLUSIONS: CD40 is expressed variably in human hepatoma and enhanced by distinct pro-inflammatory cytokines. The lack of detectable effects of CD40 ligation does not support a major role of this molecule in hepatocellular carcinoma biology.

Transjugular intrahepatic portosystemic shunt in Vienna--a decade later.

Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) for therapy of portal hypertension has been available in Vienna, Austria, since 1991. Ten years of experience with this technique led the Vienna TIPS Study Group to retrospectively analyse characteristics and outcome of all patients undergoing TIPS in Vienna between 1991 and 2001. Survival and subgroup analyses were performed using Mann Whitney U-tests, log-rank tests, Spearman's correlation and Kaplan-Meier analyses. A total of 523 patients underwent TIPS; 23 for acute variceal bleeding, 350 for prevention of variceal bleeding, and 109 for therapy of refractory ascites. Portal hypertension was caused by cirrhosis in 503 patients; 20 presented with other diseases. 253 patients died within the study period, median follow-up was 5.07 years, median survival 4.51 years. The 3-month, 1-year, 3-year, and 5-year survival rates were 83%, 71%, 57%, and 49%, respectively. Etiology of cirrhosis had no effect on survival; patients with TIPS for refractory ascites had poorer survival rates than those undergoing TIPS for prevention of rebleeding. TIPS is a safe and effective therapy for patients with portal hypertension. The first decade of TIPS in Vienna has shown, in line with other publications, that good criteria for patient selection, effective post-interventional management, and close cooperation between internists, interventional radiologists and liver-transplant centers are the key for a good outcome.

von Willebrand factor antigen: a novel on-treatment predictor of response to antiviral therapy in chronic hepatitis C genotypes 1 and 4.

BACKGROUND: Levels of von Willebrand factor antigen (vWF-Ag) increase during combination antiviral therapy of chronic hepatitis C (CHC). The present study investigates the association between these changes in vWF-Ag levels and response to treatment. METHODS: Changes in levels of vWF-Ag on antiviral combination treatment in 184 patients with CHC genotype 1 or 4 infections were measured prospectively and effect on response was studied. RESULTS: High on-treatment levels of vWF-Ag were associated with relapse (P<0.01) and low on-treatment levels with sustained virological response (SVR). Receiver operating characteristic curve analysis showed that vWF-Ag levels of <300% at week 12 of therapy have a positive predictive value (PPV) of 78% for SVR. In early virological response (EVR) patients, the PPV of vWF-Ag levels <300% at week 12 was 74%. An even higher PPV of 88% in complete EVRs (undetectable HCV RNA at week 12) was observed for the same cutoff value at week 12. CONCLUSIONS: On-treatment levels of vWF-Ag can be utilized as an additional predictive marker for response to antiviral therapy. This is especially relevant in EVR patients because EVR alone only has a PPV of 58-72% on SVR, which increased to 74%, when factoring in vWF-Ag levels <300% at week 12, and to 88% in complete EVRs; therefore, measurement of vWF-Ag levels at week 12 is helpful. EVR patients that are above the cutoff values for vWF-Ag that make SVR very probable might profit from an extension of therapy to 72 weeks.

Long-term outcome in patients with ulcerative colitis treated with intravenous cyclosporine A is determined by previous exposure to thiopurines.

BACKGROUND AND AIM: Rescue therapy with intravenous cyclosporine A (CsA) helps to avoid colectomy in a substantial proportion of patients with severe ulcerative colitis (UC) but the impact on long-term outcome remains unclear. Therefore, we aimed to define predictive factors for colectomy in patients treated with intravenous CsA for severely active UC. METHODS: A retrospective, single-center study with a minimum follow-up of 18 months was performed. RESULTS: A total of 64 patients were evaluable (median age 33 years [range 17-80 years], female 54.7%). Median intravenous CsA dose was 4 mg/kg/day (range 2-5mg/kg/day). After a median follow-up of 65 months (range 2-160 months), 19 patients (29.7%) underwent colectomy, 15 within 18 months. Of the various baseline parameters tested, only previous non-response to thiopurine treatment (p=0.006) was associated with an increased risk of colectomy. During 18 months follow-up, thiopurine-naïve patients receiving thiopurine maintenance therapy after intravenous CsA (32/64, 50.0%) underwent colectomy in 12.5% of cases. The colectomy rate was 27.3% among 22 patients previously non-responsive to thiopurines who continued treatment after intravenous CsA, compared to 50.0% in the 10 patients who discontinued thiopurines prior to intravenous CsA or who never received thiopurines (p=0.037). CONCLUSIONS: The long-term colectomy rate after intravenous CsA in patients with severely active UC was relatively low in our series compared to the literature. Concomitant treatment with thiopurines was the only predictor for a reduced risk of colectomy.