Low prevalence of liver-kidney microsomal autoantibodies of type 1 (LKM(1)) in hepatitis C seropositive subjects on Crete, Greece

BACKGROUND: Hepatitis C is a serious problem on the Greek island of Crete, where a high prevalence of antibodies against hepatitis C (anti-HCV) has recently been reported. This article reports the findings of a study carried out in Crete, which investigated the prevalence of serum autoantibodies in patients with chronic hepatitis C. PATIENTS AND METHODS: One hundred and forty two patients (59 men and 83 women), who were found anti-HCV seropositive in two hospitals and two Primary Health Care Centres in Crete, were eligible. Sixty healthy blood donors (46 men, 14 women), which were negative to anti-HCV, were used as the control group. They were randomly selected from those attending Rethymnon Hospital. Autoantibodies were identified using the indirect immunofluorescence (IFL) technique on human epithelial cells from larynx cancer (HEp-2 cells), rat liver-kidney-stomach substrate (CT3) and Chrithidia Luciliae (CL). RESULTS: Serum autoantibodies were detected in 104 HCV patients, yielding an overall prevalence of 73.2%. The most frequent autoantibodies were antinuclear antibodies (ANA), positive in 72 patients (50.7%). Anti-smooth muscle antibodies (ASMA) were detected in 33 patients (23.2%). Only one patient was positive for LKM(1) autoantibodies. No autoantibodies were found in 38 patients (26.7%). Autoantibodies were also found in 5 out of the 60 examined healthy blood donors (8.3%). CONCLUSIONS: Autoantibodies, mainly ANA and ASMA are very common in HCV seropositive patients from Crete. By contrast LKM(1) autoantibodies are exceptionally rare in these patients

A giant adrenal lipoma presenting in a woman with chronic mild postprandial abdominal pain: a case report

<p>Abstract</p> <p>Introduction</p> <p>Adrenal lipomas are rare, small, benign, non-functioning tumors, which must be histopathologically differentiated from other tumors such as myelolipomas or liposarcomas. They are usually identified incidentally during autopsy, imaging, or laparotomy. Occasionally, they may present acutely due to complications such as abdominal pain from retroperitoneal bleeding, or systemic symptoms of infection. We report a giant adrenal lipoma (to the best of our knowledge, the second largest in the literature) clinically presenting with chronic mild postprandial pain.</p> <p>Case presentation</p> <p>A 54-year-old Caucasian woman presented several times over a period of 10 years to various emergency departments complaining of long-term mild postprandial abdominal pain. Although clinical examinations were unrevealing, an abdominal computed tomography scan performed at her most recent presentation led to the identification of a large lipoma of the left adrenal gland, which occupied most of the retroperitoneal space. Myelolipoma was ruled out due to the absence of megakaryocytes, immature leukocytes, or erythrocytes. Liposarcoma was ruled out due to the absence of lipoblasts. The size of the lipoma (16 × 14 × 7 cm) is, to the best of our knowledge, the second largest reported to date. After surgical resection, our patient was relieved of her symptoms and remains healthy six years postoperatively.</p> <p>Conclusion</p> <p>Physicians should be aware that differential diagnosis of mild chronic abdominal pain in patients presenting in emergency rooms may include large adrenal lipomas. When initial diagnostic investigation is not revealing, out-patient specialist evaluation should be planned to enable appropriate further investigations.</p

Co-expression of fibrotic genes in inflammatory bowel disease; A localized event?

IntroductionExtracellular matrix turnover, a ubiquitous dynamic biological process, can be diverted to fibrosis. The latter can affect the intestine as a serious complication of Inflammatory Bowel Diseases (IBD) and is resistant to current pharmacological interventions. It embosses the need for out-of-the-box approaches to identify and target molecular mechanisms of fibrosis.Methods and resultsIn this study, a novel mRNA sequencing dataset of 22 pairs of intestinal biopsies from the terminal ileum (TI) and the sigmoid of 7 patients with Crohn’s disease, 6 with ulcerative colitis and 9 control individuals (CI) served as a validation cohort of a core fibrotic transcriptomic signature (FIBSig), This signature, which was identified in publicly available data (839 samples from patients and healthy individuals) of 5 fibrotic disorders affecting different organs (GI tract, lung, skin, liver, kidney), encompasses 241 genes and the functional pathways which derive from their interactome. These genes were used in further bioinformatics co-expression analyses to elucidate the site-specific molecular background of intestinal fibrosis highlighting their involvement, particularly in the terminal ileum. We also confirmed different transcriptomic profiles of the sigmoid and terminal ileum in our validation cohort. Combining the results of these analyses we highlight 21 core hub genes within a larger single co-expression module, highly enriched in the terminal ileum of CD patients. Further pathway analysis revealed known and novel inflammation-regulated, fibrogenic pathways operating in the TI, such as IL-13 signaling and pyroptosis, respectively.DiscussionThese findings provide a rationale for the increased incidence of fibrosis at the terminal ileum of CD patients and highlight operating pathways in intestinal fibrosis for future evaluation with mechanistic and translational studies

Primary biliary cirrhosis and autoimmune cholangitis are not associated with coeliac disease in Crete

BACKGROUND: An increased prevalence of coeliac disease in patients with primary biliary cirrhosis has been recently reported. However, in other studies the association has not been confirmed. There have been no formal attempts to systematically evaluate patients with autoimmune cholangitis for coeliac disease. METHODS: Sera from 62 patients with primary biliary cirrhosis, 17 with autoimmune cholangitis and 100 blood donors were screened for anti-gliadin, anti-endomysial, anti-reticulin, and IgA class antibodies to guinea pig liver-derived tissue transglutaminase. Eighteen untreated coeliacs served as methodological controls. Analyses were performed by using the χ(2) and Fischer's exact tests. RESULTS: Anti-gliadin antibodies were detected in 21% of patients with primary biliary cirrhosis, 35% of patients with autoimmune cholangitis, and 3% of controls (p < 0.001). IgA class gliadin antibodies positivity was more pronounced in patients with Scheuer's stage III-IV disease (p < 0.05). Anti-transglutaminase antibodies were detected in 10% and in 18% of patients with primary biliary cirrhosis and autoimmune cholangitis respectively (p < 0.001). Anti-reticulin and anti-endomysial antibodies were negative in all patients. Duodenal biopsies were performed in 59% and 71% of patients with primary biliary cirrhosis and autoimmune cholangitis respectively, tested positive for at least one antibody class. No histological features of coeliac disease were found. CONCLUSIONS: We were unable to demonstrate an increased risk of coeliac disease in patients with primary biliary cirrhosis and autoimmune cholangitis. Our results confirm the previously reported high prevalence of false-positive anti-gliadin and guinea pig liver-derived anti-tissue transglutaminase antibodies in patients with chronic liver disease

The role of myofibroblasts in the fibrotic process in Crohn's disease

Background and Aims.Colonic epithelial cells and adjacent subepithelial myofibroblasts are important counterparts in the pathophysiology of intestinal inflammation and fibrosis, respectively. We investigated the possible crosstalk between them, while focusing on the mucosal inflammation pathways that potentially trigger intestinal fibrosis.Methods.We studied the effects of pro-inflammatory cytokines (IL-1α, TNF-α, IFN-γ) on human colonic epithelial cell lines and the effects of epithelial cell-conditioned media on primary human colonic subepithelial myofibroblasts along with the corresponding 18CO cell line. Readouts included TGF-β isoforms, TIMP-1, collagen, matrix metalloproteinases MMP-2,MMP-9 activity and SEMF migration.Results.Pro-inflammatory cytokines upregulated generation of profibrotic TGF-β and TIMP-1 in colonic epithelial cells but had no effect on myofibroblasts. TNF-α or IL-1α induced MMP-9 activity in myofibroblasts, but IFN-γ inhibited that phenomenon. Colonic epithelial cells pretreated with pro-inflammatory cytokines induced MMP-9 production by subepithelial myofibroblasts, which was dependent on endothelin receptor A signalling in myofibroblasts. Moreover, colonic epithelial cells treated with pro-inflammatory cytokines doubled totalcollagen production in myofibroblasts, but this effect was independent of TGF-β, CTGF, TF and endothelin. Myofibroblasts isolated from Crohn’s disease patients showed similar responses, with the exception of increased basal collagen production. Myofibroblast migration/mobility was directly reduced by TNF-α or IFN-γ, but increased by TGF-β1. However, conditioned media from epithelial cells pretreated with pro-inflammatory cytokines decreased migration/mobility of myofibroblasts.Conclusions.Our study indicates that colonic epithelial cells may respond to an inflammatory milieu by inducing myofibroblast functions similar to those observed during intestinal fibrosis.Υπόβαθρο/στόχοι.Επιθηλιακά κύτταρα και παρακείμενοι υποεπιθηλιακοί μυοϊνοβλάστες μετέχουν στην παθοφυσιολογία εντερικής φλεγμονής και ίνωσης αντίστοιχα. Ερευνήσαμε την πιθανή επικοινωνία μεταξύ τους, επικεντρωνόμενοι σε μονοπάτια φλεγμονής του βλεννογόνου που ενδεχομένως πυροδοτούν εντερική ίνωση.Μέθοδοι.Μελετήσαμε την επίδραση των προφλεγμονωδών κυτταροκινών IL-1α, TNF-α, IFN-γ σε ανθρώπινες επιθηλιακές κυτταρικές σειρές και των υπερκειμένων τους σε πρωτογενείς ανθρώπινους υποεπιθηλιακούς μυοϊνοβλάστες παχέος εντέρου και στην αντίστοιχη κυτταροσειρά 18CO ως προς TGF-β ισομορφές, TIMP-1, κολλαγόνο, δραστικότητα μεταλλοπρωτεασών MMP-2, -9 και μετανάστευση μυοϊνοβλαστών.Αποτελέσματα.Οι προφλεγμονώδεις κυτταροκίνες αύξησαν την έκκριση των προϊνωτικών TGF-β και ΤΙΜΡ-1 σε επιθηλιακά κύτταρα, αλλά όχι σε μυοϊνοβλάστες. Οι TNF-α και IL-1α προκάλεσαν επαγωγή MMP-9 δραστικότητας σε μυοϊνοβλάστες, αλλά η IFN-γ ανέστειλε αυτό το φαινόμενο. Επιθηλιακά κύτταρα προδιεγερμένα με τις προφλεγμονώδεις κυτταροκίνες προκάλεσαν δραστικότητα MMP-9 στους μυοϊνοβλάστες, εξαρτώμενη από σηματοδότηση του υποδοχέα Α των ενδοθηλινών της μεμβράνης τους. Επιπλέον, επιθηλιακά κύτταραπροεπωασμένα με τις προφλεγμονώδεις κυτταροκίνες διπλασίαζαν τη συνολική παραγωγή κολλαγόνου στους μυοϊνοβλάστες, ανεξάρτητα από TGF-β, CTGF, TF και ενδοθηλίνες. Μυοϊνοβλάστες απομονωμένοι από ασθενείς με νόσο του Crohn επέδειξαν όμοιες απαντήσεις, με την εξαίρεση της ιδιοσυστασιακά αυξημένης βασικής παραγωγής κολλαγόνου. Η μετανάστευση/κινητικότητα των μυοϊνοβλαστών μειώθηκε άμεσα από τον TNF-α και την IFN-γ, αλλά αυξήθηκε από τον TGF-β1. Ωστόσο, επώαση με υπερκείμενο επιθηλιακών προδιεγερμένων με τις προφλεγμονώδεις κυτταροκίνες μείωσε τη μετανάστευση/κινητικότητα των μυοϊνοβλαστών.Συμπεράσματα.Η μελέτη μας καταδεικνύει ότι τα κολονικά επιθηλιακά κύτταρα δυνητικά απαντούν σε φλεγμονώδες περιβάλλον προκαλώντας λειτουργίες των υποκείμενων μυοϊνοβλαστών παρόμοιες με αυτές που παρατηρούνται σε εντερική ίνωση

Nutritional Assessment of Greek Liver Cirrhosis Patients: Mini Nutritional Assessment Predicts Mortality

Malnutrition is highly prevalent in liver cirrhosis (LC). It increases as the severity of the disease progresses and it is related to poor survival. The objectives of the study were the nutritional assessment of Greek LC patients, using various nutritional assessment and screening tools, and the comparison of their predictive value for mortality. In total, 137 (77 male) consecutive LC patients (median age: 67 years) were assessed with subjective global assessment (SGA) and mini nutritional assessment (MNA) questionnaires, anthropometrics, handgrip strength (HGS) tests, and bioelectric impedance analysis (BIA), in comparison to a control group of 148 healthy people. Disease severity was assessed using the model for end-stage liver disease (MELD) scores. Patients were followed up for a median of 19 months. Survival curves were calculated using the Kaplan&ndash;Meier method. In total, 60% and 43% of patients were of adequate nutritional status by SGA and MNA, respectively, which was confirmed by most anthropometric measurements. MNA and SGA scores correlated significantly with anthropometrics and BIA-derived parameters. Besides the MELD score, mid-arm circumference (MAC), triceps skinfold (TSF), BIA&rsquo;s phase angle (Pha), and MNA predicted mortality in cirrhotic patients. The nutritional assessment demonstrated an unexpectedly high prevalence of well-nourished LC patients. MNA was a strong predictor of mortality