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Background: The existence of reliable prognostic indices is of paramount importance in the management of cirrhosis. Both the model for end-stage liver disease (MELD) score and the older Child-Pugh (CP) scores are widely used. The albumin-bilirubin (ALBI) score, initially used in hepatocellular carcinoma, has not been thoroughly investigated in cirrhosis. The aim of this study was to compare the prognostic accuracy of ALBI, MELD, MELD with sodium (MELD-Na), CP, and the corrected for creatinine CP scores in a genetically homogeneous Cretan cirrhotic population. Methods: One hundred ninety-five outpatients or hospitalized cirrhotics (127 male, median age 66 years) were studied over a period of 2 years and ALBI, platelet-albumin-bilirubin, MELD, MELD-Na, CP score, and 2 types of modified CP score (CP-I and CP-II) with serum creatinine were calculated and correlated with survival. Results: ALBI had an optimum balance between sensitivity and specificity (area under the curve 0.704, 95% confidence interval [CI] 0.630-0.778) compared to the other scores. In the multivariate analysis, the only factors independently associated with death were the ALBI score (hazard ratio [HR] 2.51, 95%CI 1.69-3.73; P

Background The outcome of primary biliary cholangitis (PBC) is affected by both genetic and environmental factors. Objective The aim of this study was to study the effect of smoking on liver histology and mortality in a genetically homogeneous population having PBC. Patients and methods Smoking and drinking habits at diagnosis (based on standard criteria) were recorded in 171 Cretan patients with PBC (163 women). A total of 148 patients had a liver biopsy. Odds ratios were calculated with logistic regression analysis. Kaplan-Meier curves were used for mortality estimation. Results Smoking was associated with alcohol consumption of more than 20 g/day [adjusted odds ratio (AOR)=2.20, 95% CI: 1.029-4.099], severe steatosis (AOR=5.31, 95% CI: 2.019-9.919), and fibrosis stage F3-F4 (AOR=1.21, 95% CI: 1.015-3.031). Heavy smoking, years of passive smoking, and serious necroinflammatiοn were independent factors associated with advanced fibrosis after adjustment for sex, age, BMI, and alcohol consumption in multivariate analysis. For every pack-year increase in smoking intensity, there was a 3.2 times higher likelihood of advanced fibrosis (95% CI: 2.018-6.294). Increased mortality was found in smokers with advanced PBC. Conclusion There is an association between smoking, whether active or passive, and advanced fibrosis in PBC. Mortality is increased in smokers with advanced disease at presentation.

Objectives Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting a significant proportion of the general population. Recently, randomized clinical trials have been conducted examining the efficacy of silymarin in individuals with NAFLD, with conflicting results. The aim of this meta-analysis was to evaluate the efficacy of silymarin in the treatment of NAFLD by examining changes in liver biochemistry, body mass index, and liver histology. Methods We searched major electronic databases PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, as well as gray-literature sources, up to June 2020 for randomized clinical trials examining the efficacy of treatment with silymarin in individuals with NAFLD compared to placebo. The primary outcomes were changes in the mean values of transaminases (alanine aminotransferase and aspartate aminotransferase). Secondary outcomes included changes in body mass index and liver histology. Quality analysis was performed with the risk-of-bias tool 2.0. We synthesized results using weighted mean differences for continuous outcomes, along with 95% confidence intervals. Results In the meta-analysis, eight randomized clinical trials were included. A cutoff level of 0.05 was considered to provide statistically significant results. Silymarin treatment led to a statistically significant greater reduction in the levels of transaminases compared to placebo, irrespective of weight loss. Conclusions Silymarin seems to be effective in reducing transaminase levels in individuals with NAFLD. Despite the statistical benefits, we call attention to potential flaws related to the quality of the included studies. Further well-designed studies should be carried out to examine whether this reduction in transaminase levels corresponds to histologic improvement.

Primary biliary cholangitis (PBC) is a chronic progressive cholestatic disease characterized by destruction of small- and medium-sized intrahepatic bile ducts. It is no longer a rare disease, since many new asymptomatic cases are incidentally identified. Liver biopsy is diagnostically critical but not always feasible or practical to be performed. Many potential, noninvasive, markers have been proposed to replace liver biopsy and further provide the assessment of disease severity and ultimate prognosis. In this review, we evaluated serum biomarkers proposed for diagnosis, extent of fibrosis, disease prognosis and attempts for early prediction of treatment response. Older biochemical and immunological markers are presented along with recent reports including the role of microRNAs and promising results based on proteomics and metabolomics.

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.

Background and aims The aims of this study were to prospectively screen cirrhotic patients with arterial blood gas test and albumin perfusion scan, identify those fulfilling the classic hepatopulmonary syndrome (HPS) criteria, correlate with clinical parameters, and evaluate the survival of patients with HPS compared with those without HPS in a genetically homogenous Cretan cirrhotic population. Materials and methods Data on consecutive 102 patients within 1 year were collected and analyzed. All patients underwent a technetium 99m-macroaggregated albumin perfusion lung scan (Tc-MAA). Diagnosis of HPS was based on the presence of the quantitative index Tc-MAA≥6% and a [P(A-a)O2]≥15 mm Hg (≥20 mm Hg for patients over >64 y). Results In 94/102 patients, complete scintigraphic data were available. In total, 24 (26%) patients fulfilled the diagnostic criteria of HPS; 95.8% of them had mild-to-moderate HPS. In 8 patients the Tc-MAA scintigraphy could not be interpreted. There was no difference in HPS between decompensated (24.6%) and compensated cirrhosis (27.3%). In the multivariate analysis only the quantitative index was significant for the diagnosis of HPS (P=0.001, odds ratio; 95% confidence interval, 7.05; 2.27-21.87). Kaplan- Meier survival curves indicated a similar overall prognosis for patients diagnosed with HPS (P=0.105). Conclusions HPS is a frequent complication of cirrhosis. Mild-to-moderate HPS has no significant effect on survival of cirrhotic patients. The quantitative Tc-MAA test is a reliable tool for diagnosis.

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.

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. Keywords Hepatocellular carcinoma, cirrhosis, non-alcoholic fatty liver disease, HCV, hepatocellular carcinoma Ann Gastroenterol 2017; 30 (3): 357-363

BACKGROUND AND AIMS Critical illness-related corticosteroid insufficiency has been reported in acute variceal bleeding (AVB). In cirrhosis, free serum cortisol (FC) is considered optimal to assess adrenal function. Salivary cortisol (SC) is considered a surrogate for FC. We evaluated FC and its prognostic role in AVB. METHODS Total serum cortisol, SC, cortisol-binding globulin, and FC (Coolens' formula) were evaluated in AVB (n=38) and in stable cirrhosis (CC) (n=31). A Cox proportional hazards model was evaluated for 6-week survival. RESULTS In AVB, the median FC and SC levels were higher with worse liver dysfunction [Child-Pugh (CP) A/B/C: 1.59/2.62/3.26 μg/dl, P=0.019; CPA/B/C: 0.48/0.897/1.81 μg/ml, P

Objective The mechanisms of immune tolerance to hepatitis B virus (HBV) in children infected perinatally or early in infancy still remain unclarified. We aimed to study the genetic variants of immune factors implicated in viral–host interaction in children who were born to HBV-positive mothers and who had different clinical outcome. Methods Mannose-binding lectin gene (mbl2) codon 54, codon 57, and promoter 221 variants, tumor necrosis factor α (TNF-α) 308G/A, and vitamin D receptor (VDR) ApaI and TaqI genotypes were analyzed in three groups of children born to HBV-positive mothers: children with chronic infection (n=33), those with resolved infection (n=36), and those naive for HBV (n=33). Results TNF-α −308G allele frequency was found to be increased in children with chronic infection compared with children who were not affected by HBV [risk ratio (RR) 1.12, 95% confidence interval (CI) 1.0–1.25; P=0.050]. The VDR ApaI A allele tended to be more frequent in children with chronic infection than in those with resolved HBV infection (RR 1.27, 95% CI 0.95–1.67; P=0.071). The VDR ApaI α allele in ApaI and TaqI joint haplotype αT was more frequent in children with resolved infection than in those with chronic infection (RR 1.74, 95% CI 0.97–3.13; P=0.049). Conclusion Our results suggest that TNF-α and vitamin D pathways may be involved in the susceptibility to and outcome of HBV infection acquired early in life.

Eur J Clin Invest 2012 Abstract Background Activin-A is a molecule of the TGF superfamily, implicated in liver fibrosis, regeneration and stem cell differentiation. However, data on activins in liver diseases are few. We therefore studied serum levels of activin-A in chronic liver diseases. To identify the origin of activin-A, levels in the hepatic vein were also estimated. Materials and methods Nineteen controls and 162 patients participated in the study: 39 with hepatocellular carcinoma (HCC: 19 viral associated and 20 alcohol associated), 18 with chronic hepatitis C (CHC), 47 with primary biliary cirrhosis (26 PBC stage I–II and 21 stage IV), 22 with alcoholic cirrhosis (AC, hepatic vein blood available in 16), 20 with HCV cirrhosis (hepatic vein blood available in 18) and 16 patients with alcoholic fatty liver with mild to moderate fibrosis but no cirrhosis. Results Activin-A levels were significantly increased (P

Choledochal cyst is a relatively uncommon disease which is characterized by congenital dilatation of the intra and/or extrahepatic part of the biliary tree. Type IVa choledochal cysts are managed surgically through total excision of the entire extrahepatic part of the abnormal bile ducts and a simultaneous hepaticoenterostomy. Postoperative anastomotic stricture after excision of choledochal cysts and hepaticojejunostomy is a well-known late complication. We report a case of a 17-year-old female in whom gadoxetic acid-enhanced magnetic resonance cholangiography assisted in the evaluation of a biliary stricture following bile duct procedures after choledochal cyst correction surgery.

Anemia is an important complication of inflammatory bowel disease (IBD). Recent data suggest that hepcidin is a major mediator of anemia with a central role in iron homeostasis and metabolism. The aim of this study was to evaluate the serum levels of hepcidin and its prohormone, prohepcidin, in patients with IBD in comparison with healthy controls.One hundred patients with IBD [49 ulcerative colitis (UC), 51 Crohn's disease (CD)] and 102 healthy controls were enrolled. Serum hepcidin and prohepcidin levels were measured by commercially available enzyme-linked immunosorbent assays kits. Their relationship with clinical and laboratory parameters of UC and CD was assessed.Median hepcidin levels were significantly higher in both patients with UC and patients with CD compared with healthy controls (P0.0001). Median prohepcidin levels were significantly lower in patients with IBD compared with healthy controls (P = 0.03). In the univariate analysis, serum hepcidin was significantly negatively correlated (r = -0.36, P = 0.0003), whereas serum prohepcidin was positively correlated (r = 0.65, P0.0001) with the hemoglobin levels. Significant correlations of both hepcidin (r = 0.34, P = 0.0007) and prohepcidin (r = -0.21, P = 0.04) with ferritin levels were found in patients with IBD. Serum hepcidin was also correlated with disease activity (for UC, r = 0.36, P = 0.009) and C-reactive protein (r = 0.29, P = 0.004). After multivariate analysis serum hepcidin levels remained significantly correlated with ferritin (P = 0.0008) and disease activity (for UC, P = 0.004).Serum hepcidin and prohepcidin levels are significantly altered in patients with IBD compared with healthy controls. This finding suggests a substantial role of these two hormones in the development of anemia in IBD.

Hyaluronan, leptin, laminin and collagen IV have been used extensively for the assessment of liver fibrosis. The aim of this study was to assay these markers in the peripheral and hepatic vein blood of primary biliary cirrhosis (PBC) patients and to study their ability to discriminate early from advanced disease.Sera from 62 PBC patients were compared to 60 controls, 44 chronic Hepatitis C, 38 hepatocellular carcinoma and 34 viral cirrhosis patients. Serum from the hepatic vein of 15 cirrhotic PBC patients and 17 patients with viral cirrhosis was also assayed.All disease groups had significantly increased levels of hyaluronan and collagen IV, compared to controls, while laminin was significantly increased only in viral cirrhosis. Hyaluronan levels were statistically different between early (54.5 ng/ml; 95%CI 27.3-426.9) and late PBC (154.5 ng/ml; 95%CI 55.3-764.4, p0.05). The area under the curve (AUC) for the identification of late PBC was 0.74 for hyaluronan, 0.63 for leptin, 0.59 for laminin and 0.70 for collagen IV. Hyaluronan had high sensitivity and NPV in identifying late stages of PBC (96% and 90%, respectively). Short term UDCA had no effect on these markers.No single measurement can differentiate between advanced and early fibrosis in PBC. However serum hyaluronan is a promising single serum marker for longitudinal studies in PBC.

Background and Aim: T-lymphocyte migration is implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). CXC chemokines MIG, IP-10, and I-TAC act by binding to CXCR3 receptor on T-lymphocytes. We investigated the role of these chemokines and their receptor in patients with UC, CD, and normal controls (NC). Methods: Chemokine expression and serum levels were examined in colonic biopsies from patients and NC using reverse transcription–polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. HT-29 and Caco2 colonic epithelial cells were studied following in vitro stimulation with proinflammatory (Th1) and Th2-derived cytokines. CXCR3 receptor expression was assessed in CD3+ peripheral blood lymphocytes (PBL) from patients and NC and in stimulated Jurkat leukaemia cells, using RT-PCR and flow cytometry. Results: Full size CXCR3 mRNA (FS) expression was found in CD3+ PBL from controls and UC, but not from CD patients. In contrast, CD3+ PBL from CD patients showed a marked mRNA expression of the spliced variant CXCR3 (TV). This finding explains the high expression of CXCR3 on CD3+ PBL from CD patients in flow cytometry. Increased chemokine expression and production was found in colonic biopsies and serum from CD compared to UC patients and controls. Stimulation of epithelial cells with proinflammatory cytokines significantly induced chemokine production. The addition of Th2 cytokines had an inhibitory effect. Stimulation of Jurkat cells with cytokines and supernatant conditioned media from epithelial cells induced CXCR3TV expression. Conclusions: These data demonstrate that PBL from CD patients express a spliced variant of the CXCR3 receptor and suggest a role for the colonic epithelial cells in T-lymphocyte migration in intestinal inflammation.

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.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.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) (P0.0001). 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.PAI-1 plasma levels are increased whereas TAFI levels are decreased in IBD patients. These results suggest an imbalance of fibrinolysis in IBD.

Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated.

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.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.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.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.

Pancreatic autoantibodies (PAbs) have been suggested as a specific but not sensitive marker for Crohn's disease (CD). The aim of this study was to assess the value of detecting PAbs in Greek patients with ulcerative colitis (UC) and CD. Sera were collected from 150 patients with IBD (73 with UC and 77 with CD), 31 cases with non-IBD intestinal inflammation, 16 cases with other autoimmune diseases, and 104 healthy controls. Determination of PAbs was performed by a standard indirect immunofluorescence technique. PAbs were detected in 18 of 73 (24.7%) samples from UC patients and in 32 of 77 (41.6%) samples from CD patients. The prevalence of positive PAbs was significantly higher in CD than in UC (P = 0.04). None of the 104 samples from healthy controls and the 31 cases with non-IBD intestinal inflammation had detectable PAbs. One patient with Sjogren's syndrome was PAbs positive. No association of PAbs with IBD activity, IBD localization, or medical treatment was found. Patients with stenotic CD had a significantly higher prevalence of PAbs positivity (60%) compared with patients with inflammatory (28.6%) and fistulizing (41.2%) disease (P = 0.02). The prevalence of PAbs in Greek CD patients was found to be similar to that in previous reports. In contrast to these studies we found also increased prevalence of PAbs in UC patients. These findings suggest that PAbs should be considered as a specific marker for IBD rather than for CD.

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.

Kupffer cells may be involved in liver fibrogenesis through production of TGF-beta1. Their role in fibrinolysis is less clear. Octreotide, a synthetic analogue of somatostatin, is often used in cirrhotic patients. Its effect on Kupffer cells was studied. Isolated rat Kupffer cells were cultured in the presence of lipopolysaccharide and/or octreotide. TGF-beta1, leptin, collagenase (MMP-1), and urokinase-type plasminogen activator (uPA) were assessed in supernatants by ELISA, and MMP-2 and MMP-9 by zymography. Kupffer cells produced large amounts of MMP-1 and lipopolysaccharide induced a significant (P < 0.02) early increase. Octreotide and lipopolysaccharide caused a synergistic effect on MMP-1 secretion. By contrast, MMP-9 production stimulated by lipopolysaccharide was suppressed by octreotide. Kupffer cells produced a basal amount of uPA, significantly increased after lipopolysaccharide or octreotide incubation (P < 0.001). Large amounts of TGF-beta1 were produced in a time-dependent manner by unstimulated Kupffer cells. Lipopolysaccharide and octreotide, alone or in combination, induced a significant inhibition of this production (P < 0.01). Kupffer cells did not produce leptin, a recently identified mediator of liver fibrosis, or MMP-2. Kupffer cells may play a significant role in liver fibrinolysis. Octreotide, acting on TGF-beta1, uPA, and MMP-1 production, may be a useful agent for fibrosis resolution.

Oxidative stress and depletion of antioxidants may play a key role in the pathogenesis of inflammatory bowel disease (IBD)-related intestinal damage. A new automated assay for the determination of blood total antioxidant capacity (TAC), based on the crocin bleaching method, has been used for the measurement of TAC and corrected TAC (cTAC) in patients with ulcerative colitis (UC) and Crohn's disease (CD) in comparison to healthy controls (HC). Ninety-four patients with UC, 97 patients with CD, and 72 HC were included in this study. Serum TAC was measured in all patients and controls on an Olympus AU-600 chemistry analyzer using a TAC kit. cTAC was calculated from TAC after subtraction of the interactions due to endogenous uric acid, bilirubin and albumin. Mean serum TAC as well as cTAC levels were significantly lower in both UC and CD patients compared with HC (P

The survival of 85 anti-mitochondrial antibody (AMA)-positive (mean Mayo risk score, 5.11) and 19 AMA-negative (mean Mayo risk score, 4.77) primary biliary cirrhosis patients, under ursodeoxycholic acid not subjected to liver transplantation, was compared with the estimated survival of a simulated control group of untreated patients created with the updated Mayo model and a control group from the general population. In the first 7 years 3 AMA-negative patients died, versus 12 under the Mayo model (P = 0.01), and 10 AMA-positive patients, versus 26 under the Mayo model (P < 0.005), with 7 expected deaths from the general population (P < 0.0001). At 10 years the cumulative survival differed in the treated patients overall (P < 0.0001) but not in the early primary biliary cirrhosis (stages I-II) patients compared to the general population. Therefore the survival of our patients treated with ursodeoxycholic acid is higher than that predicted from the Mayo model. Early treatment may prolong survival.

Hepatocellular carcinoma (HCC) patients have an increased risk for venous thromboembolism, mainly portal venous thrombosis (PVT). The aim of this study was to assess the role of acquired and hereditary thrombotic risk factors in HCC patients. Thirty-one patients with HCC, 30 patients with cirrhosis but without HCC or PVT, and 48 matched healthy controls were studied. Mean levels of plasma protein C, protein S, antithrombin, and serum lipoprotein (a) were significantly lower in patients with HCC and in the cirrhotic group compared to the healthy controls. Mean serum homocysteine levels were significantly higher in patients with HCC compared to cirrhotics and healthy controls. The prevalence of activated protein C resistance, factor V Leiden mutation, prothrombin gene mutation G20210GA, and C677T methylenetetrahydrofolate reductase polymorphism was not significantly different among the three groups. In conclusion, thrombophilic defects are common in HCC patients and they might contribute to the observed thrombotic complications in this malignancy.

Background: Experimental studies demonstrate that hepatitis B virus may induce nitric oxide (NO) production in infected hepatocytes. Its presence in acute hepatitis B patients has not been studied. Methods: Serum levels of nitric oxide and its regulatory pro-inflammatory cytokines were detected in 15 patients with uncomplicated acute hepatitis B, 19 blood donors and 15 chronic hepatitis B patients. Cytokines were determined with an immunoassay. Nitric oxide was measured as the serum metabolic products of nitrates and nitrites using a modification of the Griess reaction. Results: All detected cytokines were increased in acute hepatitis B patients compared to healthy controls (p

/Laminin and collagen IV have been proposed as extracellular matrix serum markers. Because fibrosis is a major complication of inflammatory bowel disease, serum concentrations of laminin and collagen IV were measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared with inflammatory and healthy controls.Laminin and collagen IV serum concentrations were measured in 170 patients with inflammatory bowel disease (86 UC and 84 CD), in 23 patients with other causes of intestinal inflammation, and in 80 matched healthy controls using commercially available enzyme linked immunosorbent assays. Laminin and collagen IV concentrations were correlated with disease activity, type, localisation, and treatment.Mean (SD) serum laminin concentrations were 281.0 (110.1) ng/ml in patients with UC, 275.6 (106.7) ng/ml in patients with CD, 192.0 (17.8) ng/ml in healthy controls, and 198.5 (32.5) ng/ml in inflammatory controls. Mean (SD) serum collagen IV concentrations were 72.8 (22.9) ng/ml in patients with UC, 71.0 (18.2) in patients with CD, 79.8 (12.2) ng/ml in healthy controls, and 88.9 (24.6) ng/ml in inflammatory controls. There was a significant difference among the four groups (p0.0001) for both markers. There was a strong correlation between serum laminin, but not collagen IV, and disease activity in both diseases. No significant association was found between these markers and disease localisation or disease type.Serum concentrations of laminin are increased, whereas serum concentrations of collagen IV are decreased, in patients with inflammatory bowel disease. They may be useful surrogate markers for sustained inflammation and tissue remodelling.

To evaluate the use of pentavalent (V) technetium 99m (99mTc) dimercaptosuccinic acid (DMSA) scintigraphy for the assessment of disease activity in patients with inflammatory bowel disease (IBD).99mTc (V) DMSA scintigraphy was performed in 76 patients. There were 36 patients with active IBD (11 with ulcerative colitis, 25 with Crohn disease), 28 patients with inactive disease (eight with ulcerative colitis, 20 with Crohn disease), and 12 patients with miscellaneous bowel disease. Sensitivity and specificity of 99mTc (V) DMSA scintigraphy in the diagnosis of IBD were calculated. In the group with active IBD, the disease activity and laboratory indices, as well as the endoscopic and histologic activity, were compared with the scanning activity index. Correlation coefficients between them were calculated with the Spearman rank test.99mTc (V) DMSA scintigraphy had a 92% (33 of 36) sensitivity and an 86% (24 of 28) specificity in the detection of active IBD. A significant correlation between disease activity indices and scintigraphy score was demonstrated. Endoscopic and histologic activity was significantly correlated (P =.005 and.02, respectively, overall disease activity) with the scanning activity score. Of the group of patients with miscellaneous bowel disease, three with ischemic colitis had negative findings at scintigraphy.99mTc (V) DMSA scintigraphy provides a noninvasive, practical, and accurate assessment of IBD activity.

Background and aims. Initiation of a fibrotic process has been suggested as part of the intestinal response to chronic inflammation in inflammatory bowel disease. YKL-40 has been proposed as a new serum marker of fibrosis. We studied compared the serum levels of YKL-40 in patients with ulcerative colitis or Crohn's disease with inflammatory and healthy controls. Patients and methods. YKL-40 serum levels were measured in 179 patients with inflammatory bowel disease (94 ulcerative colitis, 85 Crohn's disease), in 23 with intestinal inflammation of other causes, and 70 matched healthy controls using a commercially available enzyme-linked immunosorbent assay. YKL-40 levels were assessed in terms of disease activity, type and localization. Results. Mean serum YKL-40 levels were 102.6±82.7 ng/ml in ulcerative colitis patients and 112.2±83.7 ng/ml in Crohn's disease patients, significantly higher than in healthy controls (64.1±21.4 ng/ml) but not significantly different from inflammatory controls (77.8±23.1 ng/ml). Disease activity and C-reactive protein levels were significantly correlated with YKL-40 levels in both ulcerative colitis and Crohn's disease. Crohn's disease patients with ileum localization had significantly higher YKL-40 levels than those with ileocolonic or colonic disease. Patients with stenotic disease had mean YKL-40 levels not significantly different than those with nonstenotic disease. Conclusion. Serum levels of YKL-40 are increased in patients with inflammatory bowel disease, and this is associated with the inflammatory process rather than with the degree of fibrosis.

Acute pancreatitis runs an unpredictable course. We prospectively analyzed the prognostic usefulness of four different scoring systems in separately assessing three variables; acute pancreatitis severity, development of organ failure and pancreatic necrosis.78 patients with acute pancreatitis were studied prospectively. Data pertinent to scoring systems were recorded 24 hours (APACHE II and III scores), 48 hours (Ranson score) and 72 hours (Balthazar computed tomography severity index) after admission. Statistical analysis was performed by using receiver operating characteristic curves and by comparing likelihood ratios of positive test (LRPT) for all three outcome variables.44 patients were classified as mild and 34 as severe pancreatitis. When we compared LRPT, only that for the Balthazar score (11.2157) was able to generate large and conclusive changes from pretest to post-test probability in acute pancreatitis severity prediction. LRPT were 2.4157 for Ranson, 4.0980 for APACHE II and 3.6670 for APACHE III score. The APACHE II and III scores and Ranson criteria performed slightly better than the Balthazar score in predicting organ failure (LRPT: 4.0667, 3.2892, 3.0362 and 1.7941 respectively), while when predicting pancreatic necrosis the APACHE II and III performed slightly better than the Ranson score (LRPT: 2.0769, 2.7500 and 1.7813 respectively).In all outcome measures the APACHE scores generate small and of similar extent changes in probability. The Balthazar score is superior to other scoring systems in predicting acute pancreatitis severity and pancreatic necrosis. However the Ranson and APACHE scores perform slightly better with respect to organ failure prediction.

Hypercoagulable states have been suggested to play an important role in the pathogenesis of ischemic colitis. Since protein Z is, as recently demonstrated, important in the regulation of coagulation, we investigated the plasma levels of protein Z in connection to factor V Leiden (FVL) anti-phospholipid antibodies in patients with a definite diagnosis of ischemic colitis. The plasma levels of protein Z were measured using a commercially available enzyme-linked immunosorbent assay in 33 patients with ischemic colitis, 13 patients with diverticulitis, and 33 healthy controls. Mean plasma protein Z levels were 1.38 ± 0.52 μg/ml in patients with ischemic colitis and were significantly lower compared to healthy controls (1.86± 0.49 μg/ml) patients with diverticulitis (1.72 ± 0.53 μg/ml) (P = 0.001). Protein Z deficiency was found in patients cases with ischemic colitis (18.2%) compared to one with diverticulitis (7.7%) one healthy control (3.0%). In conclusion, our results suggest that low plasma protein Z levels may play a role in the disease development in some cases with ischemic colitis.

Background. Autonomic function in inflammatory bowel disease has not yet been studied by means of analysis of 24-hour heart rate variability. Aim. To measure heart rate variability in inflammatory bowel disease patients in remission. Patients and methods. Study population comprised 27 patients with inflammatory bowel disease in remission and 28 healthy, sex- and age-matched controls. Two frequency ranges were analysed: low frequency (0.06–0.15 Hz) and high frequency (0.15–0.40 Hz). Results. Mean values of low frequency and low frequency/high frequency ratio were lower in patients than in controls (p

Retroperitoneal fibrosis has been described as a rare occurrence during the course of inflammatory bowel disease, mainly Crohn's disease. This is the third report on retroperitoneal fibrosis occurring during the course of ulcerative colitis. A 62-year-old male patient with a 5-year history of ulcerative colitis developed stenosis of the left ureter due to retroperitoneal fibrosis. Treatment consisted in surgically releasing the ureter from the mass and steroids. During a 2.5-year follow-up, renal function was stable and ulcerative colitis in remission. Important aspects of this case are the moderate course of ulcerative colitis, ultrasound confirmation of normal kidney structure before manifestation of fibrosis, hypertension diagnosed four years before retroperitoneal fibrosis, a non-functioning kidney at diagnosis, and reduction of retroperitoneal mass after steroid treatment. Retroperitoneal fibrosis, although a rare disease entity should be considered when a patient with ulcerative colitis develops otherwise unexplained renal insufficiency.

Background & Aims: Hypercoagulable states may play an important role in the pathogenesis of colon ischemia. Aim of this study was to assess this hypothesis investigating the role of acquired and hereditary thrombotic risk factors in patients with definite diagnosis of colon ischemia. Methods: We compared the frequency of antiphospholipid antibodies, protein C, protein S, and antithrombin deficiencies, factor V Leiden, prothrombin gene mutation G20210GA, and methylenetetrahydrofolate reductase C677T in 36 patients (23 men, 13 women; mean age, 64.8 years) with colon ischemia, 18 patients with diverticulitis, and 52 healthy controls. Results: The prevalence of antiphospholipid antibodies was significantly higher in patients with colon ischemia compared with inflammatory and healthy controls (19.4% vs. 0% and 1.9%). Among genetic factors, only factor V Leiden was significantly associated with colon ischemia (22.2% vs. 0% and 3.8%). A combination of thrombophilic disorders was found in 25% of the cases. Overall, one or several prothrombotic abnormalities were present in 26 patients (72%). Conclusions: A comprehensive thrombophilic screening in colon ischemia reveals a congenital or acquired thrombophilic state in 72% of patients. Hereditary and acquired thrombotic risk factors may play an important role in the disease pathogenesis.

Background: Evidence exists that somatostatin and octreotide might have different effects on hepatic haemodynamics. Aim: The investigation of the effects of somatostatin and its octapeptide analogue, octreotide, on sinusoidal pressure measured by the wedged hepatic venous pressure in patients with cirrhosis or chronic hepatitis and the correlation with the levels of hepatic vein NO. Methods: Patients were randomly assigned to receive an injection of either 250 μg somatostatin (n=14: cirrhosis six, chronic hepatitis eight) or an injection of 125 μg octreotide (n=19: cirrhosis nine, chronic hepatitis 10) during hepatic vein catheterization. Baseline wedged hepatic venous pressure was measured, followed by measurements at 2, 5, 10 and 15 min after the injection of the drug. Nitrites/nitrates of the hepatic vein were measured before the injection and after 15 min. Results: Both agents showed a similar qualitative but a different quantitative haemodynamic profile. No change in the wedged hepatic venous pressure was observed during the first 2 min after the injection of both drugs. This was followed by a decrease: 18% at 5 min (N.S.), 23% at 10 min (P

We investigated whether the mean platelet volume would be a useful marker in the evaluation of inflammatory bowel disease activity.Complete blood count, C-reactive protein, erythrocyte sedimentation rate, serum thrombopoietin and erythropoietin, plasma beta-thromboglobulin, and platelet factor 4 were measured in 93 patients with ulcerative colitis, 66 patients with Crohn's disease, and 38 healthy blood donors. Disease activity was assessed by the Clinical Colitis Activity Index in patients with ulcerative colitis and by the Crohn's Disease Activity Index in patients with Crohn's disease.Mean platelet count was increased in patients with active compared to inactive ulcerative colitis (p0.05), and in patients with active compared to inactive Crohn's disease (p = 0.0002) or healthy controls (p0.0001). On the other hand, mean platelet volume was significantly decreased in patients with active compared to inactive ulcerative colitis (p = 0.02) or healthy controls (p0.0001), and in patients with active compared to inactive Crohn's disease (p = 0.0005) or healthy controls (p0.0001). Mean platelet volume was inversely correlated with the white blood cell count (r = -0.17, p = 0.02), C-reactive protein (r = -0.46, p = 0.009) and erythrocyte sedimentation rate (r = -0.28, p = 0.008). No significant correlations were found between mean platelet volume and serum thrombopoietin or erythropoietin levels; however, a strong negative correlation between mean platelet volume and beta-thromboglobulin (r = -0.34, p0.0001) and platelet factor 4 (r = -0.30, p = 0.0002) was observed.Mean platelet volume is significantly reduced in active inflammatory bowel disease and is negatively correlated with the known inflammatory bowel disease activity markers and the platelet activation products. We propose that mean platelet volume provides a useful marker of activity in inflammatory bowel disease.

The combined measurement of perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) and anti-Saccharomyces cerevisiae mannan antibodies (ASCA) has recently been suggested as a valuable diagnostic approach in inflammatory bowel disease (IBD). The aim of this study was to assess the value of detecting pANCA and ASCA in the differentiation between ulcerative colitis (UC) and Crohn's disease (CD) in a Greek population with IBD.Sera were collected from 157 patients with IBD (97 with UC, 56 with CD, and four with indeterminate colitis) and 150 healthy controls. Determination of pANCA was performed by a standard indirect immunofluorescence technique on ethanol-fixed granulocytes and ASCA by an ELISA assay.In patients with UC, sensitivity, specificity, positive predictive value, and negative predictive value of the pANCA test was 67%, 84%, 93%, and 46% respectively. These values did not change significantly when the combination of positive pANCA and negative ASCA was used. ASCA test in diagnosing CD yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 54%, and 81%. The combination of pANCA negative and ASCA positive increased the positive predictive value to 77% and it was associated with small bowel disease.A positive pANCA test in Greek patients has a diagnostic value in confirming a diagnosis of UC. Measurement of pANCA and ASCA together has a rather limited value in the differential diagnosis between UC and CD but may be of help in studying disease heterogeneity.

OBJECTIVES: The combined measurement of perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) and anti–Saccharomyces cerevisiae mannan antibodies (ASCA) has recently been suggested as a valuable diagnostic approach in inflammatory bowel disease (IBD). The aim of this study was to assess the value of detecting pANCA and ASCA in the differentiation between ulcerative colitis (UC) and Crohn’s disease (CD) in a Greek population with IBD. METHODS: Sera were collected from 157 patients with IBD (97 with UC, 56 with CD, and four with indeterminate colitis) and 150 healthy controls. Determination of pANCA was performed by a standard indirect immunofluorescence technique on ethanol-fixed granulocytes and ASCA by an ELISA assay. RESULTS: In patients with UC, sensitivity, specificity, positive predictive value, and negative predictive value of the pANCA test was 67%, 84%, 93%, and 46% respectively. These values did not change significantly when the combination of positive pANCA and negative ASCA was used. ASCA test in diagnosing CD yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 54%, and 81%. The combination of pANCA negative and ASCA positive increased the positive predictive value to 77% and it was associated with small bowel disease. CONCLUSIONS: A positive pANCA test in Greek patients has a diagnostic value in confirming a diagnosis of UC. Measurement of pANCA and ASCA together has a rather limited value in the differential diagnosis between UC and CD but may be of help in studying disease heterogeneity.

Twenty-two different protein measurements were taken in the serum and ascitic fluid of fifty consecutive patients in an attempt to investigate which tests are the most reliable for the differential diagnosis of ascites. Serum and ascitic fluid total proteins (TPR), albumin (ALB), lactate (LAC), ferritin (FER), C3 and C4 complement factors, C-reactive protein (CRP), ceruloplasmin (CER), alpha2-macroglobulin (alpha2MG), haptoglobin (HAP), alpha1-antitrypsin (alpha1AT), alpha1-acid glycoprotein (alpha1AG), transferrin (TRF), immunoglobulins IgG, IgA, IgM and cytokines such as interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were measured to distinguish between malignant and cirrhotic ascites. Correlations and non-parametric Mann-Whitney tests were used for ascitic fluid:serum ratio comparisons between the two groups. Multivariate analyses were used to determine the most significant biochemical ratio predictors for the differential diagnosis and a recursive partitioning model was constructed. Highly positive correlations (r>0.50) were found between the ratios IgA, IgG, IgM, CER, alpha2 MG, HAP, alpha1AT, alpha1AG and TRF. There was evidence that TPR, ALB, LAC, FER, IgG, CER, alpha2MG, alpha1AT, alpha1AG, TRF and IL-8 ascitic fluid:serum ratios are significnatly higher in patients with malignant neoplasms than in cirrhotics. In the recursive partitioning model the most significant parameters were found to be the ratios of albumin and IL-1alpha. The model fitted allowed for 100% correct classification of ascites. In conclusion, we have shown that a simple and very accurate model based on two ascitic fluid: serum measurements is able to differentiate between malignant and non-malignant ascites.

A balance between endothelins (ET) and nitric oxide (NO) might interfere with liver haemodynamics and disease progression in various liver diseases. Increased levels of endothelin 1 (ET-1) and nitrites and nitrates (NOx, the end products of NO metabolism) have been reported in hepatocellular carcinoma (HCC), but the balance has not been studied. The purpose of this study was to assess the ratio of NOx to ET-1 in patients with virus-related hepatocellular carcinoma and to investigate its correlation with the extent of the disease. Eighteen patients with virus-related HCC (six Okuda stage I, six Okuda stage II and six Okuda stage III) were included in the study and were compared with 22 patients with viral cirrhosis (14 decompensated, eight compensated) and seven normal controls. ET-1 was measured with an ELISA assay and NOx with a modification of the Griess reaction. Patients with virus-related HCC had the highest levels of circulating ET-1 and NOx (13.24 +/- 0.82 pg/ml and 112.28 +/- 18.56 micromol/l) compared to compensated cirrhosis (9.47 +/- 0.50 pg/ml, P < 0.004 and 54.47 +/- 2.36 micromol/l, P < 0.01), decompensated cirrhosis (9.57 +/- 0.32 pg/ml, P < 0.001 and 90.20 +/- 11.23 micromol/l, NS) and normal controls (8.84 +/- 0.61 pg/ml, P < 0.001 and 51.17 +/- 6.18 micromol/l, P < 0.01). There was a significant increase of ET-1 and NOx at HCC stage III compared to HCC stages I and II, cirhotics and controls. HCC stage III patients also had a NOx/ET-1 ratio that was higher than HCC stages I and II patients, normal controls and patients with compensated cirrhosis. Virus-related HCC patients have high levels of circulating ET-1, compared to compensated or decompensated cirrhosis. Highest levels of ET-1 are produced in Okuda III tumours. NOx are also increased but only in Okuda stage III tumours. The NOx/ET-1 ratio is increased in virus-related HCC and DC. This increase may account for the known increase in tumour blood flow.

Objectives Information about the epidemiology of acute upper gastrointestinal bleeding (UGIB) in southern Europe is very limited and especially in Greece non-existent. Our study sought to determine the current epidemiology of acute UGIB (incidence, mortality and case fatality) in the prefecture of Heraklion-Crete. Design/methods From February 1998 to February 1999, we prospectively obtained data on all patients with acute UGIB in the prefecture of Heraklion-Crete. All patients who were permanent residents of the prefecture of Heraklion, aged 16 years and over with acute UGIB were included in the study. Results During this period, 353 cases of acute UGIB were included in the study. The overall incidence of acute UGIB is 160/100 000 adults per year with a male-to-female ratio of 1.7 and a mean age 66.2 ± 17.1 years. The incidence rises from 30 in those aged under 30 years to 609 in those aged over 75 years. The overall population mortality was 9/100 000 adults per year. Overall case fatality during hospitalization was 5.6%. All deaths occurred in patients older than 60 years. One or more comorbid illnesses were noted in 61% of cases. Recent intake of non-steroidal antiinflammatory drugs (NSAIDs) was reported in 49% of the cases. The most common recorded diagnoses were erosive disease in 108 (30.5%) patients, duodenal ulcer in 97 (27.4%) and gastric ulcer in 75 (21.2%). Rebleeding occurred in 41 patients (12%). Twelve patients (3.3%) had surgery during hospitalization. Conclusions The overall annual incidence of acute UGIB in the prefecture of Heraklion-Crete is one of the highest reported in Europe and increases appreciably with age. Both population mortality and case fatality are slightly lower compared to those reported in most previous studies.

Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. A recently identified mechanism for thrombophilia, the poor anticoagulant response to activated protein C, has been suggested as one of the leading risk factors for thrombosis. The aim of this study was to evaluate the frequency of thrombophilic abnormalities, including activated protein C-resistance (APCR), in Greek patients with ulcerative colitis (UC) and Crohn's disease (CD).Forty-eight patients with UC, 36 with CD, and 61 matched healthy controls (HC) were studied. Cases with presence of lupus anticoagulant, use of anticoagulants or heparin, and pregnancy were excluded. Disease activity in CD was evaluated by use of the Crohns Disease Activity Index (CDAI) score and in UC by the Truelove-Witts grading system. Plasma levels of protein C, free protein S, antithrombin III (AT-III), activated protein C resistance (APCR), and fibrinogen were determined in IBD patients, as well as in HC. All the cases and controls with abnormal APCR were further studied by genetic testing for the factor V Leiden mutation.Mean fibrinogen levels in UC and CD patients were significantly elevated (p0.0001), compared with HC. The mean values of free protein S, as well as mean APCR, were significantly lower in UC and CD patients than in the HC (p0.0001). Seven (five UC and two CD) of 84 IBD patients (8.3%) and three of the HC (4.9%) had the factor V Leiden mutation. No significant difference was observed for the other thrombophilic parameters. Fibrinogen levels and profound free protein S deficiency were found related to disease activity.Thrombophilic defects are common in Greek patients with IBD and they could interfere either in the disease manifestation or in the thrombotic complications.

Retractile mesenteritis is an extremely rare disease characterised by a non-specific inflammatory and fibrotic process of the mesenteric adipose tissue, which is usually accompanied by pain and a variety of other abdominal symptoms. We describe here the case of a patient with retractile mesenteritis presenting with prolonged high-grade fever and autoimmune haemolytic anaemia without abdominal symptoms. The patient’s illness was complicated by chylous ascites. Diagnosis was suspected by computed tomography and confirmed histologically following exploratory laparotomy. The patient was treated with prednisone and azathioprine, and he had a rapid improvement in anaemia and fever relief, but no substantial change in the mesenteric lesions. Our case adds autoimmune haemolytic anaemia to the wide spectrum of manifestations of retractile mesenteritis and implies the possible involvement of immune mechanisms in the pathogenesis of the disease.

In recent years hyperhomocysteinemia has been established as a new risk factor for arterial and venous thrombosis. Since patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events, we studied the prevalence and clinical significance of hyperhomocysteinemia in Greek patients with ulcerative colitis (UC) and Crohn's disease (CD). In 108 consecutive fasting IBD patients (53 UC and 55 CD) and 74 healthy controls (HC), a standard record of various clinical thrombotic risk factors was completed by interview, and fasting serum concentrations of total homocysteine (tHcy), folate, cobalamin, creatinine, cholesterol, HDL, LDL, and triglycerides were measured. The concentration (mean ± sd) of serum tHcy was significantly higher in UC (15.9 ± 10.3 μmol/liter) and CD patients (13.6 ± 6.5) than in controls (9.6 ± 3.4, P < 0.05). Both UC and CD patients had lower levels of folate than HC (P < 0.05). Covariance analysis of age, gender, and all clinical variables indicated that the differences in homocysteine levels between IBD patients and HC remain significant even after adjustment for these covariates. In conclusion, mild hyperhomocysteinemia is common in Greek IBD patients and may account for the increased thrombotic risk of these patients.

Primary biliary cirrhosis and ulcerative colitis are two diseases with many features of autoimmunity. Thirteen cases of coexistence of the two diseases have been reported in the literature so far. Patients are usually younger and more often males than the ordinary primary biliary cirrhosis patient, while the colitis is mild and easily controllable. In a homogeneous population of 550,000 inhabitants of the island of Crete, 412 cases of ulcerative colitis and 82 individuals with primary biliary cirrhosis or autoimmune cholangitis have been identified. In two cases, coexistence of the two diseases was found. Immunological screening for AMA positivity in 150 ulcerative colitis sera disclosed no further cases. Prevalence of primary biliary cirrhosis in ulcerative colitis patients seems at least 30 times higher than in the general population in our area. A possible immunological link between the two diseases is discussed.

Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Anti-cardiolipin (aCL) antibodies have been shown to be associated with thrombosis. Recently, the antibodies against the anti-cardiolipin cofactor beta2-glycoprotein I (a(beta2)GPI) have been found with higher specificity for thrombosis. The presence of these antibodies was assessed in 128 patients with IBD [83 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)] and 100 healthy controls (blood donors). Patients with UC and CD had a significantly higher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (HC) (3%). Eleven IBD patients (8.6%) but no HC had a(beta2)GPI. None of the IBD patients with a history of thrombosis had aCL and only one of them (a UC patient with deep vein thrombosis of the right leg) had a high titer of IgG a(beta2)GPI. In conclusion, these data show that both aCL and a(beta2)GPI are significantly associated with IBD but further studies are needed to determine the significance of our findings.

Objective: To investigate the clinical characteristics of advanced hepatocellular carcinoma (HCC) in Crete and to analyse the natural course of the untreated disease. Participants: Seventy-three patients (62 men) were enrolled in a prospective 4-year study. Clinical and virological parameters were recorded. Diagnosis was based on either ultrasound guided liver biopsy or a pathognomonic increase in alpha-fetoprotein plus compatible imaging. Methods: Statistical analysis was performed using histograms, contingency tables and one-way analyses of variance to analyse the characteristics of the disease. For survival analysis Kaplan-Meier survival curves and Cox's proportional hazards models were constructed. Results: HCC in Crete is a mostly male disease (7:1 male:female ratio) and unlike in mainland Greece, it is mostly a hepatitis C virus (HCV)-related disease (54% HCV positive as opposed to only 13% in mainland Greece). Prognosis was associated with Okuda classification (Okuda stage III patients have a relative risk of dying that is seven to nine times higher than for Okuda stage I), the presence or absence of hepatitis B e antigen (HBeAg) and antibody to hepatitis B core antigen (anti-HBc). By contrast the presence of anti-HCV was not associated with a worse prognosis. A unit increase of albumin concentration was associated with an 11% decrease in the hazard rate. Conclusion: In general, Crete, despite the extremely similar population to the rest of Greece, resembles more closely the situation in Spain or Italy rather than mainland Greece.

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 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.

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).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.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).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.