Συσχετισμός υποψηφίων γονοτύπων με τη λειτουργική δυσπεψία στον ελληνικό πληθυσμό

Η προδιάθεση στη λειτουργική δυσπεψία μπορεί να επηρεαστεί από πολυμορφισμούς γονιδίων που σχετίζονται με τη φλεγμονή (CD14, παράγοντας αναστολής της μετανάστευσης μακροφάγων [MIF]), την κινητικότητα (GNB3) και την αισθητικότητα (GNB3, TRPV1). Στην παρούσα διατριβή εξετάσαμε την συσχέτιση μεταξύ των γονιδιακών πολυμορφισμών CD14 rs2569190, GNB3rs5443, MIFrs222747, και TRPV1 rs755622 με τη λειτουργική δυσπεψία (κριτήρια ROME ΙΙΙ) στον ελληνικό πληθυσμό. Μέθοδοι: Έγινε γονοτύπηση 174 δυσπεπτικών (115 με σύνδρομο επιγαστρικού πόνου, 41% με H.pyloriλοιμωξη) και 181 μαρτύρων χρησιμοποιώντας μεθόδους που βασίζονται στην αλυσιδωτή αντίδραση πολυμεράσης. Παράλληλα μετρήσαμε τη βαρύτητα των συμπτωμάτων της νόσου με μία τροποποιημένη κλίμακα βαθμολόγησης γαστρεντερικών ενοχλημάτων. Αποτελέσματα: H ομοζυγωτία για το γονότυπο ΤΤ και το Τ αλλήλιο του γονιδίου CD14 συσχετίστηκαν σημαντικά (OR [95% CI]) με τη λειτουργική δυσπεψία (2,65 [1,42 – 4,94] και 1,67 [1,23 – 2,26], αντίστοιχα). Οι γονότυποι CT, TTκαι οι συχνότητες του Τ αλληλίου τουGNB3 έδειξανεπίσης σημαντική συσχέτιση με λειτουργική δυσπεψία (2,18 [1,35 – 3,54], 3,46 [1,30 – 9,23], και 2,18 [1,48 – 3,19]). Ενώ ο ετερόζυγος γονότυπος GC MIF ήταν πιο συχνός στους δυσπεπτικούς (1,67 [1,07 – 2,60]), ο ομόζυγος γονότυπος CC και το αλλήλιο C του γονιδίουTRPV1 ήταν πιο συχνά στους μάρτυρες (0,47 [0,25 – 0,87] και 0,69 [0,51-0,92], αντίστοιχα). Κανένας πολυμορφισμός γονιδίου δεν συσχετίστηκε είτε με τον τύπο του κλινικού συνδρόμου της δυσπεψίας είτε με τη λοίμωξη απόΗ. pylori. Μεταξύ των δυσπεπτικών, ο γονότυπος CD14 TT συσχετίστηκε με χαμηλότερο σκορ επιγαστρικού πόνου (p< 0,011),ο CD14 CT γονότυποςσυσχετίστηκε με υψηλότερα σκορς επιγαστρικού καύσου και ναυτίας (p< 0,04), ενώτο σκορ για τις ερυγές ήταν χαμηλότερο (p= 0,027) σε MIF CG δυσπεπτικούς. Συμπεράσματα: Η προδιάθεση στη λειτουργική δυσπεψίασυσχετίζεται με πολυμορφισμούς των γονιδίωνCD14, GNB3, MIF και TRPV1, ενώ γονιδιακοίπολυμορφισμοί των CD14 και MIF συνδέονται επίσης με τη βαρύτητα δυσπεπτικών ενοχλημάτων.Background:Functional dyspepsia susceptibility might be influenced by polymorphisms of genes related to inflammation (CD14, MIF), motor (GNB3) and sensory dysfunction (GNB3, TRPV1). We examined the association between CD14 rs2569190, GNB3 rs5443, MIF rs222747 and TRPV1 rs755622 gene polymorphisms with functional dyspepsia (Rome III criteria) in the Greek population. Methods:We genotyped 174 dyspeptics (115 with epigastric pain syndrome; 41% H. pylori positive) and 181 controls using polymerase chain reaction-based methods and we measured disease symptoms’ burden with a modified GSRS scale. Results:Homozygous for the TT genotype and the T allele of the CD14 gene were significantly associated (OR [95%CI]) with functional dyspepsia (2.65 [1.42-4.94] and 1.67 [1.23-2.26], respectively). CT, TT genotypes and T allele frequencies of GNB3 showed also significant association with functional dyspepsia (2.18 [1.35-3.54], 3.46 [1.30-9.23] and 2.18 [1.48-3.19]).While heterozygous GC MIF genotype was more common in dyspeptics (1.67 [1.07-2.60]), homozygous CC genotype, as well as, the C allele of TRPV1 gene were more prevalent in controls (0.47 [0.25-0.87] and 0.69 [0.51-0.92], respectively). None gene polymorphism was related either to dyspepsia clinical syndrome type or to the H. pylori infection. Among dyspeptics, CD14 TT genotype was related to lower epigastric pain burden score (p<0.011); CD14 CT genotype was related to higher epigastric burning and nausea burden scores (p<0.04) while belching score was lower (p=0.027) in MIF CG dyspeptics. Conclusion:Functional dyspepsia susceptibility is related toCD14, GNB3, MIF and TRPV1 gene polymorphisms while CD14 and MIF gene variants are also associated with dyspepsia symptoms burden

Candidate genotypes associated with functional dyspepsia in Greek population

Background: Functional dyspepsia susceptibility might be influenced by polymorphisms of genes related to inflammation (CD14, MIF), motor (GNB3) and sensory dysfunction (GNB3, TRPV1). We examined the association between CD14 rs2569190, GNB3 rs5443, MIF rs222747 and TRPV1 rs755622 gene polymorphisms with functional dyspepsia (Rome III criteria) in the Greek population. Methods: We genotyped 174 dyspeptics (115 with epigastric pain syndrome; 41% H. pylori positive) and 181 controls using polymerase chain reaction-based methods and we measured disease symptoms’ burden with a modified GSRS scale. Results: Homozygous for the TT genotype and the T allele of the CD14 gene were significantly associated (OR [95%CI]) with functional dyspepsia (2.65 [1.42-4.94] and 1.67 [1.23-2.26], respectively). CT, TT genotypes and T allele frequencies of GNB3 showed also significant association with functional dyspepsia (2.18 [1.35-3.54], 3.46 [1.30-9.23] and 2.18 [1.48-3.19]). While heterozygous GC MIF genotype was more common in dyspeptics (1.67 [1.07-2.60]), homozygous CC genotype, as well as, the C allele of TRPV1 gene were more prevalent in controls (0.47 [0.25-0.87] and 0.69 [0.51-0.92], respectively). None gene polymorphism was related either to dyspepsia clinical syndrome type or to the H. pylori infection. Among dyspeptics, CD14 TT genotype was related to lower epigastric pain burden score (p<0.011); CD14 CT genotype was related to higher epigastric burning and nausea burden scores (p<0.04) while belching score was lower (p=0.027) in MIF CG dyspeptics. Conclusion: Functional dyspepsia susceptibility is related to CD14, GNB3, MIF and TRPV1 gene polymorphisms while CD14 and MIF gene variants are also associated with dyspepsia symptoms burden.Η προδιάθεση στη λειτουργική δυσπεψία μπορεί να επηρεαστεί από πολυμορφισμούς γονιδίων που σχετίζονται με τη φλεγμονή (CD14, παράγοντας αναστολής της μετανάστευσης μακροφάγων [MIF]), την κινητικότητα (GNB3) και την αισθητικότητα (GNB3, TRPV1). Στην παρούσα διατριβή εξετάσαμε την συσχέτιση μεταξύ των γονιδιακών πολυμορφισμών CD14 rs2569190, GNB3 rs5443, MIF rs222747, και TRPV1 rs755622 με τη λειτουργική δυσπεψία (κριτήρια ROME ΙΙΙ) στον ελληνικό πληθυσμό.Μέθοδοι: Έγινε γονοτύπηση 174 δυσπεπτικών (115 με σύνδρομο επιγαστρικού πόνου, 41% με H.pylori λοιμωξη) και 181 μαρτύρων χρησιμοποιώντας μεθόδους που βασίζονται στην αλυσιδωτή αντίδραση πολυμεράσης. Παράλληλα μετρήσαμε τη βαρύτητα των συμπτωμάτων της νόσου με μία τροποποιημένη κλίμακα βαθμολόγησης γαστρεντερικών ενοχλημάτων.Αποτελέσματα: H ομοζυγωτία για το γονότυπο ΤΤ και το Τ αλλήλιο του γονιδίου CD14 συσχετίστηκαν σημαντικά (OR [95% CI]) με τη λειτουργική δυσπεψία (2,65 [1,42 – 4,94] και 1,67 [1,23 – 2,26], αντίστοιχα). Οι γονότυποι CT, TT και οι συχνότητες του Τ αλληλίου του GNB3 έδειξαν επίσης σημαντική συσχέτιση με λειτουργική δυσπεψία (2,18 [1,35 – 3,54], 3,46 [1,30 – 9,23], και 2,18 [1,48 – 3,19]). Ενώ ο ετερόζυγος γονότυπος GC MIF ήταν πιο συχνός στους δυσπεπτικούς (1,67 [1,07 – 2,60]), ο ομόζυγος γονότυπος CC και το αλλήλιο C του γονιδίου TRPV1 ήταν πιο συχνά στους μάρτυρες (0,47 [0,25 – 0,87] και 0,69 [0,51-0,92], αντίστοιχα). Κανένας πολυμορφισμός γονιδίου δεν συσχετίστηκε είτε με τον τύπο του κλινικού συνδρόμου της δυσπεψίας είτε με τη λοίμωξη από Η. pylori. Μεταξύ των δυσπεπτικών, ο γονότυπος CD14 TT συσχετίστηκε με χαμηλότερο σκορ επιγαστρικού πόνου (p< 0,011), ο CD14 CT γονότυπος συσχετίστηκε με υψηλότερα σκορς επιγαστρικού καύσου και ναυτίας (p< 0,04), ενώ το σκορ για τις ερυγές ήταν χαμηλότερο (p= 0,027) σε MIF CG δυσπεπτικούς.Συμπεράσματα: Η προδιάθεση στη λειτουργική δυσπεψία συσχετίζεται με πολυμορφισμούς των γονιδίων CD14, GNB3, MIF και TRPV1, ενώ γονιδιακοί πολυμορφισμοί των CD14 και MIF συνδέονται επίσης με τη βαρύτητα δυσπεπτικών ενοχλημάτων

Endoscopic ultrasonography for gastric submucosal lesions

Gastric submucosal tumors (SMTs) are a rather frequent finding, occurring in about 0.36% of routine upper GI-endoscopies. EUS has emerged as a reliable investigative procedure for evaluation of these lesions. Diagnostic Endoscopic ultrasonography (EUS) has the ability to differentiate intramural tumors from extraluminal compressions and can also show the layer of origin of gastric SMTs. Tumors can be further characterized by their layer of origin, echo pattern and margin. EUS-risk criteria of their malignant potential are presented, although the emergence of EUS-guided fne needle aspiration (EUS-FNA) has opened new indications for transmural tissue diagnosis and expanded the possibilities of EUS in SMTs of the stomach. Tissue diagnosis should address whether the SMT is a Gastrointestinal stromal tumour (GIST) or another tumor type and evaluate the malignant potential of a given GIST. However, there seems to be a lack of data on the optimal strategy in SMTs suspected to be GISTs with a negative EUS-FNA tissue diagnosis. The current management strategies, as well as open questions regarding their treatment are also presented

Hepatocellular carcinoma after treatment cessation in non-cirrhotic HBeAg-negative chronic hepatitis B: A multicentre cohort study

Background and Aims Scarce data exist on the effect of nucleos(t)ide analogue (NA) discontinuation on hepatocellular carcinoma (HCC) risk in HBeAg-negative chronic hepatitis B (CHBe-). Therefore, we assessed whether HCC risk is increased in non-cirrhotic CHBe- patients who discontinue compared to those remaining on NAs. Methods This cohort study included 650 consecutive non-cirrhotic Caucasian or Asian patients with CHBe- without a history of HCC who discontinued NAs after a median of 5 or 3 years (cases, n = 325; Caucasians: 143, Asians: 182) or remained on NA therapy beyond 5 or 3 years respectively (controls, n = 325; Caucasians: 223, Asians: 102). Propensity score (PS) 1:1 matching was applied to adjust for patients’ origin, age and sex. Results During a median follow-up of 44 months, HCC developed in 7/325 cases and 9/325 controls or 7/245 PS-matched cases and 7/245 PS-matched controls with 5-year cumulative HCC incidence of 5.1% and 4.9% respectively (log-rank, P = .836). No difference in 5-year HCC risk was observed between cases and controls of Caucasian (3.0% vs 4.8%; log-rank, P = .510) or Asian origin (1.3% vs 2.2%; log-rank, P = .873). In both cases and controls, HCC incidence was independently associated with age and PAGE-B score. In cases alone, HCC development after NA discontinuation was associated only with pretreatment platelet counts and PAGE-B score, but not with any type of relapse or HBsAg loss. Conclusions Our findings suggest that discontinuation of effective long-term NA therapy in non-cirrhotic CHBe- patients are not associated with increased HCC risk, which is not affected by post-NA relapses and/or HBsAg loss

Immunological biomarkers as indicators for outcome after discontinuation of nucleos(t)ide analogue therapy in patients with HBeAg negative chronic hepatitis B

The optimal duration of treatment with nucleos(t)ide analogues (NAs) for patients with HBeAg‐negative Chronic Hepatitis B (CHB) is unknown. The aim of this study was to identify an immune signature associated with off‐treatment remission to NA therapy. We performed microarray analysis of PBMCs from six patients with chronic hepatitis B who stopped NA therapy (3 with off‐treatment remission, 3 with relapse) and 5 patients with chronic HBV infection (previously termed “inactive carriers”) served as controls. Results were validated using qRT‐PCR on a second group of 21 individuals (17 patients who stopped treatment and 4 controls). PBMCs from 38 patients on long‐term NA treatment were analysed for potential to stop treatment.Microarray analysis indicated that patients with off‐treatment remission segregated as a distinct out‐group. Twenty‐one genes were selected for subsequent validation. Ten of these were expressed at significantly lower levels in the patients with off‐treatment remission compared to the patients with relapse and predicted remission with AUC of 0.78‐0.92. IFNγ, IL‐8, FASLG and CCL4 were the most significant by logistic regression. Twelve (31.6%) of 38 patients on long‐term NA therapy had expression levels of all these four genes below cut‐off values, and hence were candidates for stopping treatment. Our data suggest that patients with HBeAg‐negative CHB who remain in off‐treatment remission 3 years after NA cessation have a distinct immune signature and that PBMC RNA levels of IFNγ, IL‐8, FASLG and CCL4 may serve as potential biomarkers for stopping NA therapy

Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B

Background &amp; Aims: Recently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC. Methods: We included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively. Results: HCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78–0.82). NPVs were