Increased fracture risk assessed by fracture risk assessment tool in Greek patients with Crohn's disease.

BACKGROUND: The World Health Organization has recently developed the fracture risk assessment tool (FRAX) based on clinical risk factors and bone mineral density (BMD) for evaluation of the 10-year probability of a hip or a major osteoporotic fracture. The aim of this study was to evaluate the use of the FRAX tool in Greek patients with inflammatory bowel disease (IBD). METHODS: FRAX scores were applied to 134 IBD patients [68 Crohn's disease (CD); 66 ulcerative colitis (UC)] who underwent dual-energy X-ray absorptiometry scans at the femoral neck and lumbar spine during the period 2007-2012. Calculation of the FRAX scores, with or without BMD, was made through a web-based probability model used to compute individual fracture probabilities according to specific clinical risk factors. RESULTS: The median 10-year probability of a major osteoporotic fracture for IBD patients based on clinical data was 7.1%, and including the BMD was 6.2%. A significant overestimation with the first method was found (P = 0.01). Both scores with and without BMD were significantly higher in CD patients compared with UC patients (P = 0.02 and P = 0.005, respectively). The median 10-year probability of hip fracture based on clinical data was 0.8%, and including the BMD was 0.9%. The score with use of BMD was significantly higher in CD compared with UC patients (P = 0.04). CONCLUSIONS: CD patients have significantly higher FRAX scores and possibly fracture risk compared with UC patients. The clinical FRAX score alone seems to overestimate the risk of osteoporotic fracture in Greek IBD patients.

Treatment of portal vein thrombosis in cirrhosis: a multicenter real life cοhort study.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication of cirrhosis and can be a cause or consequence of liver disease progression. It is unclear whether PVT treatment is affecting clinical outcomes in cirrhotics. METHODS: This is a multicenter study of cirrhotics with PVT, initially retrospectively and thereafter prospectively registered in a data base. We studied the impact of PVT treatment on this population for efficacy, safety and the impact on survival. In survival analysis Mantel-Cox and Wilcoxon-Breslow-Gehan tests were used. A P value of <0.05, was considered significant. For statistical computations the STATA 12.1 was used. RESULTS: Seventy-six patients were included (76% decompensated, median MELD score 12 and Child-Pugh score 7), 47% with concomitant HCC. Fifty-one patients with PVT were treated with Vitamin-K antagonists or Low-Molecular-Weight Heparin. Patients were followed up for at least 6 months after PVT diagnosis, or until death or transplantation. PV patency after 6 months was not statistically different between patients receiving or not anticoagulation (complete-partial recanalization 27.4% of treated vs. 20% of untreated, P=0.21). Median survival was statistically worse between patients treated with anticoagulation than those untreated (10 vs. 15 months, P=0.036). Less portal hypertensive bleeding and less decompensation rates were found in treated cirrhotics vs. untreated (45.8% vs. 54.2%, P=0.003 and 78% vs. 80.9%, P=0.78, respectively). Patients with HCC had worse survival when treated vs. untreated (P=0.047). CONCLUSIONS: In our cohort of cirrhotics with PVT, treatment was feasible with acceptable side effects, but without meaningful clinical benefits.

Primary biliary cirrhosis in a genetically homogeneous population: disease associations and familial occurrence rates.

BACKGROUND: Primary biliary cirrhosis (PBC) is a disease with genetic and environmental pathogenetic background. Chemicals, infectious agents, hormone therapy, reproductive history and surgical interventions have been implicated in the induction of PBC. Familial PBC has been documented in first degree relatives (FDR). Most cohort studies are genetically heterogeneous. Our study aimed to determine eventual lifestyle or disease associations and familial occurrence rates in a genetically homogeneous and geographically defined population of PBC patients. METHODS: 111 consenting PBC patients, were compared with 115 FDR and 149 controls matched for age, sex, Cretan origin and residence. All participants completed a questionnaire regarding demographics, lifestyle, medical, surgical and reproductive history. Significant variables on the univariate analysis were analyzed by multivariate analysis using a forward step-wise logistic regression model. RESULTS: Dyslipidaemia was found in 69.4% of patients, 60% of FDR and 40.9% of controls (p < 0.0001 and p = 0.003 respectively), autoimmune diseases in 36.9% of patients, 30.4% of FDR and 13.4% of controls (p < 0.0001 and p = 0.011 respectively). Hashimoto's disease (p = 0.003), Raynaud syndrome (p = 0.023) and Sjögren syndrome (p = 0.044) were significantly associated with PBC. On multivariate analysis statistically significant associations were found with primary educational level (AOR 2.304, 95% CI 1.024-5.181), cholecystectomy (AOR 2.927, 95% CI 1.347-6.362) and the presence of at least another autoimmune disease (AOR 3.318, 95% CI 1.177-6.22). Cancer history was more frequent in patients than in controls (p = 0.033). Familial PBC was found to be 9.9%. CONCLUSIONS: Dyslipidaemia and autoimmune diseases were significantly increased not only in patients as expected but also in their FDR. An increased prevalence of malignancies was found in patients. Primary educational level, cholecystectomy and the presence of at least another autoimmune disease were found as putative risk factors for PBC. No association was found with smoking, urinary tract infection or reproductive history. The reported high familial occurrence of PBC could imply screening with AMA of FDR with at least another autoimmune disease.

Spontaneous bacterial peritonitis: a prospective Greek multicenter study of its epidemiology, microbiology, and outcomes.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is an ominous complication of decompensated cirrhosis. This study aimed to assess several epidemiological, clinical, microbiological and outcome characteristics in Greek patients with SBP, as no solid representative nationwide data of this type was available. METHODS: During a 3-year period, 77 consecutive patients with SBP (61 male; median age: 67 years; model for end-stage liver disease [MELD] score: 20), diagnosed and followed in 5 tertiary liver units, were prospectively recruited and studied. Various prognostic factors for disease outcome were studied. RESULTS: Thirty-eight patients had alcohol-related cirrhosis, 17 viral hepatitis, 6 non-alcoholic steatohepatitis, 6 autoimmune liver diseases, and 10 cryptogenic cirrhosis. Hepatocellular carcinoma (HCC) was present in 23 (29.9%), whereas 10 (13%) had portal vein thrombosis. The first SBP episode at baseline was community-acquired in 53 (68.8%), while in 24 (31.1%) was hospital-acquired, with predominant symptoms abdominal pain and encephalopathy. A positive ascitic culture was documented in 36% of patients in the initial episode, with almost equal gram (+) and gram (-) pathogens, including 3 multidrug-resistant pathogens. Significant factors for 6-month survival were: higher MELD score, previous b-blocker use, lower serum albumin, higher lactate on admission and need for vasopressors, while factors for 12-month survival were MELD score and lactate. For overall survival, higher MELD score and lactate along with HCC presence were negative predictive factors. CONCLUSIONS: MELD score, lactate, albumin, HCC and treatment with vasopressors were predictive of survival in SBP patients. In hospital-acquired SBP the prevalence of difficult-to-treat pathogens was higher.

Role of ghrelin and insulin-like growth factor binding protein-3 in the development of osteoporosis in inflammatory bowel disease.

BACKGROUND: A high prevalence of bone loss is observed in patients with inflammatory bowel disease (IBD). Leptin, ghrelin, insulin-like growth factor (IGF)-1, and IGF binding protein (IGFBP)-3 have been suggested to interfere in the bone metabolism. The aim of this study was to investigate the role of these peptides in the development of osteoporosis in IBD. METHODS: One hundred and eighteen consecutive IBD patients were included. All patients underwent bone densitometry by dual energy x-ray absorptiometry at the femoral neck and lumbar spine levels. Serum samples were collected from all patients and analyzed for concentrations of the aforementioned peptides by radioimmunoassay. RESULTS: Forty (33.9%) patients were normal, 55 (46.6%) were osteopenic, and 23 (19.5%) were osteoporotic. Positive statistically significant correlations were found between body mass index (BMI), leptin, IGFBP-3 levels, and the bone mineral density (BMD) of the femoral neck and lumbar spine. Moreover, an inverse statistically significant correlation was found between BMD of the femoral neck and the lumbar spine, and age, duration of the disease, and ghrelin levels. Multivariate analysis revealed that the most significant factors associated with the BMD were age and BMI. A weak but statistically significant correlation was found between IGFBP-3 and femoral neck BMD (P=0.045) and between ghrelin and spine BMD (P=0.039). No correlation was observed between leptin and BMD. CONCLUSIONS: Low BMI is the most important independent risk factor for osteoporosis in IBD patients. There is no independent influence of leptin but ghrelin and IGFBP-3 may play a role in the bone metabolism in the IBD.

Antiglycan antibodies in Greek patients with inflammatory bowel disease.

BACKGROUND: Antiglycan antibodies have recently been reported to be associated with Crohn's disease (CD). These antibodies include anti-Saccharomyces cerevisiae mannan antibodies (ASCA), anti-laminariobioside carbohydrate antibodies (ALCA), anti-chitobioside carbohydrate antibodies (ACCA), and anti-mannobioside carbohydrate antibodies (AMCA). AIMS: The aim of this study was to evaluate their diagnostic accuracy in Greek patients with inflammatory bowel disease (IBD). METHODS: Serum was collected from 191 patients with IBD (85 with ulcerative colitis (UC) and 106 with CD), 29 cases with other causes of intestinal inflammation and 96 healthy controls. Antiglycan antibodies were measured using commercially available enzyme immunoassays. RESULTS: Higher levels of antiglycan antibodies were detected in patients with CD compared to patients with UC and controls. Although all types of antiglycan antibodies had a high specificity for diagnosing CD, their sensitivity was rather low, with best results obtained with ASCA and ALCA (41.5 and 52.8%, respectively). Increased levels of ASCA and ALCA were associated with stricturing and penetrating disease phenotype, and the need for surgery (p < 0.05). CONCLUSIONS: Antiglycan antibodies in Greek IBD patients are significantly associated with CD, and especially to phenotypes of complicated disease, with ASCA and ALCA exhibiting the highest sensitivity.

Safety and efficacy of total-dose infusion of low molecular weight iron dextran for iron deficiency anemia in patients with inflammatory bowel disease.

BACKGROUND: Intravenous iron has been suggested as a safe and effective treatment of anemia complicating inflammatory bowel disease (IBD). Low molecular weight (LMW) iron dextran has the ability to administer the patient's total iron requirement in a single infusion. AIMS: The aim of this study was to assess the safety and efficacy of the total dose of LMW iron dextran infusion for the treatment of iron deficiency in IBD. METHODS: Fifty IBD patients (27 female, 35 Crohn's disease, 15 ulcerative colitis) were included in the study. Mean +/- standard deviation (SD) hemoglobin and ferritin levels before the infusion were 9.88 +/- 1.42 g/dl and 13.9 +/- 10.9 ng/ml, respectively. A 25-mg test dose was followed by infusion of the total dose of LMW iron dextran based on the iron deficit. Several clinical and laboratory parameters were measured before and on week 4 after infusion. RESULTS: Four patients (8%) developed adverse reactions during the test infusion and did not receive the total-dose infusion. Only one patient developed an allergic reaction during the total-dose infusion. In the remaining 45 patients, the mean +/- SD iron dose that was given was 1,075 +/- 269 mg. The mean +/- SD elevation of hematocrit and hemoglobin on week 4 was 4.9 +/- 1.9% and 1.7 +/- 0.8 g/dl, respectively. Hematopoietic response was observed in 23 of 45 patients (51.1%). CONCLUSION: Total parenteral iron replacement with LMW iron dextran is an easy, safe, and effective alternative method for treating iron deficiency anemia in IBD. Harmless adverse reactions may develop in a minority of patients.

Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels in inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of thromboembolic events. Imbalance of fibrinolysis has been suggested as one of the possible pathogenetic mechanisms. As plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) are inhibitors of fibrinolysis, we studied TAFI as well as PAI-1 plasma levels in IBD patients compared with healthy controls. METHODS: A total of 132 IBD patients [68 ulcerative colitis (UC) and 64 Crohn's disease (CD)] and 50 healthy controls were enrolled. PAI-1 and TAFI plasma levels were assessed by commercially available enzyme-linked immunosorbent assay kits. Their relationship with clinical parameters of UC and CD was assessed. RESULTS: Mean plasma PAI-1 levels were significantly higher in both UC patients (3.9+/-1.3 IU/ml) and CD patients (4.0+/-1.5 IU/ml) compared with healthy controls (3.1+/-1.1 IU/ml) (P=0.01). On the other hand, mean plasma TAFI levels were significantly lower in both UC patients (14.7+/-3.1 microg/ml) and CD patients (13.3+/-3.4 microg/ml) compared with healthy controls (17.4+/-3.0 microg/ml) (P<0.0001). Patients with active disease had significantly higher PAI-1 levels compared with patients with inactive disease for both diseases (P=0.03 and P=0.01, respectively). No significant association between plasma TAFI levels and disease activity was also found. Plasma TAFI levels were significantly lower in patients with ileal CD compared with patients with colonic CD. CONCLUSION: PAI-1 plasma levels are increased whereas TAFI levels are decreased in IBD patients. These results suggest an imbalance of fibrinolysis in IBD.

Active inflammatory bowel disease: head-to-head comparison between 99mTc-hexamethylpropylene amine oxime white blood cells and 99mTc(V)-dimercaptosuccinic acid scintigraphy.

PURPOSE: Evaluation and comparison between pentavalent 99mTc dimercaptosuccinic acid (99mTc(V)-DMSA) and 99mTc-hexamethylpropylene amine oxime white blood cell (99mTc-HMPAO WBC) scintigraphy in the detection and assessment of disease activity in patients with active inflammatory bowel disease (IBD). MATERIALS AND METHODS: 99mTc(V)-DMSA scintigraphy was performed in 23 patients with active IBD and true positive 99mTc-HMPAO WBC scintigraphy. Images were considered positive when an area of increased uptake was observed. To assess severity of IBD, semi-quantitative analysis was included with reference to the uptake in the iliac crest. Comparison with endoscopic, radiological and clinical data was performed. RESULTS: The diagnostic accuracy of 99mTc-HMPAO WBC and 99mTc(V)-DMSA was 91% and 84%, respectively. A significant correlation between the findings of both radioisotopic methods and scintigraphy score was demonstrated. Endoscopic findings were significantly correlated with scintigraphic results. Kappa statistics showed a moderate to good agreement between the two scintigraphic methods. Two patients (8.8%) had negative findings with 99mTc(V)-DMSA scintigraphy (false negative results). CONCLUSION: 99mTc(V)-DMSA compared to 99mTc-HMPAO WBC could provide a simple, non-invasive alternative method for the assessment of disease activity, although it is slightly inferior to 99mTc-HMPAO WBC scintigraphy especially in the evaluation of disease localization in IBD patients.

Portal vein thrombosis in cirrhosis: diagnosis, natural history, and therapeutic challenges.

Portal vein thrombosis (PVT) is a frequent complication in cirrhosis and its prevalence increases with disease severity. Several factors are involved in the development and progression of PVT. The challenge for the management of PVT is the precise evaluation of the bleeding risk as opposed to life-threatening extension of thrombosis. Nevertheless, the impact on the progression and outcome of liver disease is unclear. A critical evaluation of the available data discloses that treating PVT in cirrhotics is safe and effective. However, there are open issues, such as which anticoagulant could represent a safer therapeutic option, and when and for how long this treatment should be administered to cirrhotic patients with PVT.

The effect of infliximab on circulating levels of leptin, adiponectin and resistin in patients with inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor alpha is a critical mediator of inflammation-related altered metabolism in inflammatory bowel disease (IBD), possibly through its interaction with adipokines, which play an important role in IBD. Infliximab is a well established antitumour necrosis factor alpha treatment in IBD. AIM AND METHODS: We studied serum levels of leptin, adiponectin and resistin in 20 IBD patients before and after infliximab treatment using commercially available enzyme-linked immunosorbent assays. The results were correlated with alterations of disease activity, BMI and C-reactive protein. RESULTS: Infliximab induced clinical response or remission in 18 out of 20 treated IBD patients. Mean serum-leptin levels were 4.6+/-0.5 and 5.1+/-0.5 ng/ml (P=0.41), mean serum-adiponectin levels were 10513.9+/-1216.9 and 9653.5+/-1031.5 ng/ml (P=0.36) and mean serum-resistin levels were 26.3+/-4.1 and 13.9+/-1.4 ng/ml (P=0.004), before and after infliximab treatment, respectively. No significant correlation between the changes of BMI, C-reactive protein or the clinical indices of activity and alterations of the examined adipokines was found. CONCLUSIONS: Serum levels of leptin and adiponectin had no significant alterations, whereas serum-resistin levels are significantly decreased after infliximab therapy in IBD patients, suggesting a possible proinflammatory status for resistin in IBD and a role as a marker of successful therapy.

Systemic treatment for hepatocellular carcinoma: Still unmet expectations.

Many patients with hepatocellular carcinoma (HCC) are diagnosed in an advanced stage, so they cannot be offered the option of curative treatments. The results of systemic chemotherapy are unsatisfactory and this has led to molecular targeted approaches. HCC develops in chronically damaged tissue due to cirrhosis in most patients. Several different cell types and molecules constitute a unique microenvironment in the liver, which has significant implications in tumor development and invasion. This, together with genome instability, contributes to a significant heterogeneity which is further enhanced by the molecular differences of the underlying causes. New classifications based on genetic characteristics of the tissue microenvironment have been proposed and key carcinogenic signaling pathways have been described. Tumor and adjacent tissue profiling seem biologically promising, but have not yet been translated into clinical settings. The encouraging first results with molecular - genetic signatures should be validated and clinically applicable. A more personalized approach to modern management of HCC is urgently needed.

Prevalence of thiopurine S-methyltransferase gene polymorphisms in patients with inflammatory bowel disease from the island of Crete, Greece.

BACKGROUND: There is evidence that genotyping for the thiopurine S-methyltransferase (TPMT) gene variants is useful for the prediction of response to thiopurine analogs (azathioprine and 6-mercaptopurine) in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of TPMT gene polymorphisms in a genetic homogenous population of IBD patients in Crete and to correlate the results with adverse reactions to thiopurine drugs. PATIENTS AND METHODS: Genotyping for the most common TPMT variants TPMT*2, TPMT*3A, TPMT3*C, and TPMT*3B was performed using the PCR-restriction fragment length polymorphism method in 223 consecutive IBD patients and 119 age-matched and sex-matched healthy controls. The hospital medical records were reviewed for thiopurine use in these patients and related adverse events. RESULTS: The prevalence of TPMT variants TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C was 1.8, 2.7, 1.3, and 1.8%, respectively. The G238C mutation was detected in four (1.8%) out of 223 patients, three (1.3%) patients were carriers of the G460A mutation, four (1.8%) of the A719G mutation, and six (2.7%) of both G460A and A719G mutations. In healthy controls, only one (0.8%) carried both the G460A and the A719G mutation, whereas TPMT*2, TPMT*3C, and TPMT*3B were not detected. None of the genotypes was homozygous. A statistically significant correlation between the presence of the G460A mutation and the development of leucopenia after the administration of thiopurines was observed (P=0.048). CONCLUSION: This study showed a lower frequency of total TPMT variants and a higher frequency of TPMT*3B in Cretan IBD patients compared with other Caucasian populations. The presence of the G460A mutation is associated with the development of leukopenia.

Long-term change in incidence and risk factors of cirrhosis and hepatocellular carcinoma in Crete, Greece: a 25-year study.

BACKGROUND: No sequential long-term data exist for Greece on the etiological evolution and incidence of cirrhosis and hepatocellular carcinoma. Therefore, we studied their etiological evolution over a period of 25 years in the island of Crete. METHODS: We studied 812 cases of cirrhosis (561 male, median age 69 years) and 321 cases of hepatocellular carcinoma (234 male, median age 70 years) from the database of our Center. Cases were classified into five-year periods according to incidence and etiology (hepatitis B, hepatitis C, alcohol, alcohol plus viral, and non-alcoholic fatty liver disease). RESULTS: Overall, there was an increase in the incidence of hepatocellular carcinoma. A significant fourfold reduction in the incidence of hepatitis C-related cirrhosis was observed, which was degraded from first to third place as a risk factor for cirrhosis. Alcohol gradually became the first risk factor in cirrhosis (1990-94: 36.1%, 2010-14: 52.3%) and carcinoma, while the steepest increase in incidence of cirrhosis and carcinoma was associated with non-alcoholic fatty liver disease. CONCLUSIONS: The incidence of cirrhosis remained constant over the years, but the incidence of hepatocellular carcinoma increased during the last decade. Risk factors for cirrhosis and hepatocellular carcinoma have changed over the past 25 years in Crete. The initial high hepatitis C virus association has significantly decreased, with alcohol now ranking first among risk factors. Non-alcoholic fatty liver disease is continually increasing and is a prominent risk factor for cirrhosis and hepatocellular carcinoma.

Role of angiogenesis in inflammatory bowel disease.

Several studies have shown alterations in vascular anatomy and physiology in inflammatory bowel disease (IBD). These findings, together with the observed upregulation of the mediators of angiogenesis in IBD patients, suggest that angiogenesis possibly contributes to the initiation and perpetuation of IBD. There is considerable evidence of an interrelationship between the mechanisms of angiogenesis and chronic inflammation in IBD. The increased expression of endothelial junction adhesion molecules found in IBD patients indicates the presence of active angiogenesis. Evidence that angiogenesis is involved in IBD was also obtained from animal models of colitis, most notably from studies of angiogenesis inhibition. Serum levels of vascular endothelial growth factor (VEGF) correlate with disease activity in human IBD and fall with the use of steroids, thalidomide, or infliximab. Pharmacological inhibition of angiogenesis, therefore, has the potential to be a therapeutic strategy in IBD. This review outlines the evidence that the rate of angiogenesis is increased in the inflamed intestine in IBD and proposes lines for future research in this field.

Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease.

BACKGROUND: There is evidence that adipocytokines play an important role in metabolism and in inflammation. Because human metabolism dramatically changes in inflammatory bowel disease (IBD) and chronic inflammation is the hallmark of the disease, we studied serum levels of leptin, adiponectin, resistin, and ghrelin in patients with ulcerative colitis (UC) and Crohn's disease (CD) in comparison with healthy controls (HC). METHODS: Leptin, adiponectin, resistin, and active ghrelin serum levels were measured in 100 IBD patients (46 UC and 54 CD) and in 60 matched HC using commercially available enzyme-linked immunosorbent assays. Leptin, adiponectin, resistin, and ghrelin levels were correlated with disease activity, type, localization, and treatment. RESULTS: Mean serum leptin levels were 10.6+/-2.0 ng/mL in UC patients, 12.5+/-2.6 ng/mL in CD patients, and 15.0+/-1.8 ng/mL in HC (P=.01). Mean serum adiponectin levels were 9514.8+/-787.8 ng/mL in UC patients, 7651.1+/-613 ng/mL in CD patients, and 7270.6+/-559.4 ng/mL in HC (P=.05). Mean serum resistin levels were 21.2+/-2.2 ng/mL in UC patients, 18.7+/-1.6 ng/mL in CD patients and 11.8+/-0.6 ng/mL in HC (P=.0002). Mean serum ghrelin levels were 48.2+/-4.2 pg/mL in UC patients, 49.4+/-4.6 pg/mL in CD patients and 14.8+/-3.0 pg/mL in HC (P<.0001). Serum levels of these adipocytokines were not correlated with either C-reactive protein levels or the clinical indices of activity. No association between serum adipocytokines levels and disease localization in both UC and CD patients was found. Only serum ghrelin was significantly higher in ileal compared with colonic CD (P=.04). CONCLUSIONS: Serum levels of adiponectin, resistin, and active ghrelin are increased whereas serum levels of leptin are decreased in patients with IBD. Further studies are needed to elucidate the role of adipocytokines in IBD.

Effectiveness of darbepoetin-alfa in combination with intravenous iron sucrose in patients with inflammatory bowel disease and refractory anaemia: a pilot study.

BACKGROUND: The combination of intravenous iron and recombinant human erythropoietin has been proved to be effective in the treatment of refractory anaemia in patients with inflammatory bowel disease (IBD). Darbepoetin-alpha (DPO) has a three-fold longer terminal half-life than erythropoietin. The purpose of this pilot study was to determine whether darbepoetin-alpha is also effective for the treatment of refractory anaemia in IBD. METHODS: Twenty IBD patients (nine ulcerative colitis and 11 Crohn's disease) and refractory anaemia received intravenous iron sucrose (total iron dose 1.3+/-0.5 g, range 0.7-1.9) and darbepoetin-alfa at the single, weekly dose of 0.9 microg/kg subcutaneously for 4 weeks. Serum erythropoietin, ferritin, transferrin, soluble transferrin receptor, C-reactive protein and interleukin-6 were measured at baseline and after treatment. RESULTS: Haematopoietic response (increase of haemoglobin > or = 2.0 g/dl) was observed in 15 out of the 20 patients (75%). The mean haemoglobin concentrations increased from 9.48+/-0.82 g/dl at baseline to 12.71+/-1.12 g/dl after treatment (P<0.0001). Mean corpuscular volume and serum ferritin levels were also significantly increased whereas mean C-reactive protein levels and endogenous erythropoietin levels significantly decreased after treatment. CONCLUSIONS: In IBD patients with refractory anaemia the administration of darbepoetin in combination with intravenous iron sucrose can raise haemoglobin levels.

The emerging role of adipocytokines as inflammatory mediators in inflammatory bowel disease.

Anorexia, malnutrition, altered body composition and development of mesenteric obesity are well known features of inflammatory bowel disease (IBD). Recent data suggest that dysregulation of protein secretion by white adipose tissue is involved in these manifestations of patients with IBD. Adipocytes are recently recognized as endocrine cells that secrete a variety of bioactive substances known as adipocytokines. There is evidence that adipocytokines are involved in inflammatory and metabolic pathways in human beings. Overexpression of adipocytokines such as leptin, adiponectin and resistin in mesenteric adipose tissue of operated patients with Crohn's disease has recently been reported, suggesting that mesenteric adipocytes in IBD may act as immunoregulating cells. Therefore, it could be suggested that adipocytokines play an important role in the disease pathogenesis. Moreover, modulators of mesenteric adipose function have been suggested as potential therapeutic drugs in IBD. In this review, the importance of white adipose tissue function and adipocytokines, is discussed with respect to IBD.

Boceprevir for chronic HCV genotype 1 infection in treatment-experienced patients with severe fibrosis or cirrhosis: The Greek real-life experience.

BACKGROUND: The aim of our study was to evaluate the safety and efficacy of triple therapy using boceprevir (BOC) with pegylated interferon (pIFN)/ribavirin (RBV) in chronic hepatitis C (CHC) genotype 1 (G1) treatment-experienced patients with advanced fibrosis or compensated cirrhosis. METHODS: We report the Greek experience on the first CHC patients who received BOC-based regimen. From September 2011 to June 2012, 26 treatment-experienced CHC patients and G1 with bridging fibrosis or compensated cirrhosis received 48 weeks of BOC+pIFN+RBV antiviral therapy. Data on complete blood counts and HCV RNA levels were obtained prior to therapy, at treatment weeks 4, 8, 12, 24, 36, 48 and 24 weeks after the end of treatment. RESULTS: A full set analysis was performed in 25 of 26 patients. Nine patients (36%) achieved sustained viral response (SVR). Ten patients (40%) stopped the therapy because of futility rules and 3 (12%) due to adverse events. Four patients (16%) developed a virological breakthrough (3 of those presented futility rules as well) and 2 (8%) relapse. All patients who achieved SVR had G 1b, 6 (67%) were non-cirrhotic and 5 (55%) had >1 log decline in baseline HCV RNA levels at week 4 of the treatment. There were no deaths, while two patients were hospitalized due to side effects. CONCLUSION: The triple therapy with BOC+pIFN+RBV in this cohort of real-life treatment-experienced CHC G1 patients and advanced liver disease was safe offering cure in the majority of those who could tolerate and complete treatment under a close monitoring.

Role of appendicitis and appendectomy in the pathogenesis of ulcerative colitis: a critical review.

Besides a genetic predisposition, a causal role of various environmental factors has been considered in the etiology of ulcerative colitis (UC). The association between appendectomy and UC has recently been the subject of intense scrutiny in the hope that it may lead to the identification of important pathogenetic mechanisms. Published data from animal models of colitis demonstrated reduction in experimental colitis after appendectomy, especially if performed at an early age. Several epidemiological case control and cohort studies have shown a strong and consistent relationship. The metaanalysis of 17 case-controlled studies showed an overall odds ratio 0.312 (95% confidence intervals = 0.261-0.373) in favor of appendectomy (p < 0.0001). One of the two recent large cohort studies is in agreement with these results, but the other failed to confirm them. All these studies have suggested that alterations in mucosal immune responses leading to appendicitis or resulting from appendectomy may negatively affect the pathogenetic mechanisms of UC. Further investigation of the role of appendectomy in UC is expected to open new fields for basic scientific research and may lead to the improvement of our understanding for the disease pathogenesis.