Study of the frequency, natural history and therapeutics of complications of liver cirrhosis

This thesis aimed: (1) to study the characteristics and prognostic patterns in a Greek cirrhotic patient population, (2) to prospectively screen cirrhotics with arterial blood gases 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 to those without HPS, (3) to compare the prognostic accuracy of ALBI, MELD, MELDNa, Child-Pugh and the corrected for Creatinine Child-Pugh score in a genetically homogeneous Cretan cirrhotic population. Commonest aetiology was hepatitis C virus (HCV, 41%) followed by alcohol (31%). The median survival time in compensated cirrhotics was 115 months (95%CI: 95-133), whereas in decompensated patients was 55 months (95%CI: 36-75). HCV patients survived longer while HBV patients had over twice the risk of death of HCV patients. The median time to decompensation was 65 months (95%CI: 51-79), with alcoholics having the highest risk (RR = 2.1 vs HCV patients). Hepatitis B virus patients had the highest risk of hepatocellular carcinoma and alcoholics the lowest. Leading causes of death: liver failure, hepatorenal syndrome, sepsis and HCC progression. 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, OR; 95% CI: 7.05; 2.27-21.87). Kaplan- Mayer survival curves indicated a similar overall prognosis for patients diagnosed with HPS (p-value= 0.105). ALBI had an optimum balance between sensitivity and specificity (AUC =0.704, 95% CI= 0.630-0.778) compared to the others scores. In the multivariate analysis, the only factors independently associated with death were the ALBI score (HR= 2.51; 95% CI: 1.69-3.73, p<0.001), the MELDNa score (HR=1.04; 95% CI: 1.00-1.09, p=0.045) and age (HR= 1.05; 95% CI: 1.03-1.07, p<0.001). When only decompensated cirrhosis was evaluated, the multivariate analysis showed that the ALBI score (HR= 3.03; 95% CI: 1.92-4.78, p<0.001) and age (HR= 1.05; 95% CI: 1.03-1.07, p<0.001) were independently associated with death. The results of this study indicate that cirrhosis aetiology and decompensation at presentation are predictors of survival. Alcoholics have the highest decompensation risk, HBV cirrhotics the highest risk of HCC and HCV cirrhotics the highest decompensation-free time. 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. ALBI score might be a better prognostic indicator of mortality in cirrhosis and due to its simplicity may substitute for the Child-Pugh scores, MELD and MELD Na score.Αυτή η διατριβή είχε ως στόχο: (1) τη μελέτη των χαρακτηριστικών και των προγνωστικών παραγόντων σε έναν ελληνικό πληθυσμό κιρρωτικών ασθενών, (2) την προοπτική μελέτη των κιρρωτικών ασθενών με αέρια αρτηριακού αίματος και σπινθηρογραφήματος αιμάτωσης πνευμόνων με μακρομόρια αλβουμίνης σεσημασμένα με ραδιενεργό τεχνήτιο (99mTc-MAA), ώστε να διαγνωστούν όσοι πληρούν τα κριτήρια του ηπατοπνευμονικού συνδρόμου (HPS) και να γίνουν συσχετίσεις με κλινικές παραμέτρους και μελέτη της επιβίωσης των ασθενών με HPS σε σύγκριση με εκείνους που δεν είχαν, (3) τη σύγκριση των προγνωστικών μοντέλων επιβίωσης ALBI, MELD, MELDNa, Child-Pugh και τα τροποποιημένα με βάση την κρεατινίνη ορού Child-Pugh score.Η πιο συχνή αιτιολογία της κίρρωσης ήταν ο ιός της ηπατίτιδας C (HCV, 41%) ακολουθούμενος από το αλκοόλ (31%). Ο διάμεσος χρόνος επιβίωσης στους ασθενείς με αντιρροπούμενη κίρρωση ήταν 115 μήνες (95% CI: 95-133), ενώ στους ασθενείς με μη αντιρροπούμενη κίρρωση ήταν 55 μήνες (95% CI: 36-75). Οι κιρρωτικοί ασθενείς με ηπατίτιδα C επέζησαν περισσότερο, ενώ οι ασθενείς με ηπατίτιδα Β είχαν πάνω από το διπλάσιο κίνδυνο θανάτου σε σχέση με αυτούς με ηπατίτιδα C. Ο διάμεσος χρόνος για τη ρήξη της αντιρρόπησης ήταν 65 μήνες (95% CI: 51-79), με τους αλκοολικούς να έχουν τον υψηλότερο κίνδυνο (RR = 2,1 έναντι ασθενών με ηπατίτιδα C). Οι ασθενείς με κίρρωση λόγω της ηπατίτιδας Β είχαν τον υψηλότερο κίνδυνο ανάπτυξης ηπατοκυτταρικού καρκίνου και οι αλκοολικοί το χαμηλότερο. Κυριότερες αιτίες θανάτου ήταν η ηπατική ανεπάρκεια, το ηπατονεφρικό σύνδρομο, η σηψαιμία και η εξέλιξη του ηπατοκυτταρικού καρκίνου.Όσον αφορά το ηπατοπνευμονικό σύνδρομο δεν υπήρχε διαφορά μεταξύ των ασθενών με αντιρροπούμενη (24,6%) και μη αντιρροπούμενη κίρρωση (27,3%). Στην πολυπαραγοντική ανάλυση μόνο ο ποσοτικός δείκτης του σπινθηρογραφήματος ήταν σημαντικός για τη διάγνωση του HPS (p = 0,001, OR, 95% CI: 7,05, 2,27-21,87). Οι καμπύλες επιβίωσης Kaplan-Mayer έδειξαν παρόμοια συνολική πρόγνωση για ασθενείς που είχαν διαγνωστεί με HPS (τιμή p = 0,105).Το ALBI είχε τη βέλτιστη ισορροπία μεταξύ ευαισθησίας και ειδικότητας (AUC = 0,704, 95% CI = 0,630-0,778) σε σύγκριση με τα υπόλοιπα αποτελέσματα. Στην πολυπαραγοντική ανάλυση, οι μόνοι παράγοντες που σχετίζονται ανεξάρτητα με το θάνατο ήταν η τιμή του ALBI (HR = 2,51, 95% CI: 1,69-3,73, p <0,001), η τιμή του MELDNa (HR = 1,04, 95% CI: 1,00-1,09, p = 0,045) και η ηλικία (HR = 1,05, 95% CI: 1,03-1,07, p <0,001). Όταν αξιολογήθηκε μόνο η αντιρροπούμενη κίρρωση, η πολυπαραγοντική ανάλυση έδειξε ότι η τιμή του ALBI (HR = 3,03, 95% CI: 1,92-4,78, p <0,001) και η ηλικία (HR = 1,05, 95% CI: 1,03-1,07, p <0,001 ) συνδέονταν ανεξάρτητα με το θάνατο.Τα αποτελέσματα αυτής της μελέτης δείχνουν ότι η αιτιολογία της κίρρωσης και η ρήξη της αντιρρόπησης στη διάγνωση είναι προγνωστικοί παράγοντες επιβίωσης. Οι αλκοολικοί έχουν τον υψηλότερο κίνδυνο ρήξης της αντιρρόπησης, οι ασθενείς με κίρρωση λόγω ηπατιτίδας Β τον υψηλότερο κίνδυνο ανάπτυξης ΗΚΚ και οι ασθενείς με κίρρωση λόγω ηπατιτίδας C το μεγαλύτερο χρονικό διάστημα έως τη ρήξη της αντιρρόπησης. Το HPS είναι μια συχνή επιπλοκή της κίρρωσης. Το ήπιο έως μέτριο HPS δεν έχει σημαντική επίδραση στην επιβίωση των κιρρωτικών ασθενών. Ο ποσοτικός δείκτης του σπινθηρογραφήματος αιμάτωσης πνευμόνων με μακρομόρια αλβουμίνης σεσημασμένα με ραδιενεργό τεχνήτιο (99mTc-MAA)είναι ένα αξιόπιστο εργαλείο για τη διάγνωση. Η βαθμολογία ALBI μπορεί να είναι ένας καλύτερος προγνωστικός δείκτης της θνησιμότητας στην κίρρωση και λόγω της απλότητάς του μπορεί να αντικαταστήσει τις βαθμολογίες Child-Pugh, MELD και MELD Na

Paired comparison between water and nutrient drink tests in healthy volunteers

CONTEXT: Drink tests constitute an inexpensive and non-invasive tool, which has been proposed to discriminate individuals with altered fluid intake, as dyspeptics. However, their use in everyday clinical practice is still limited as standardization still lacks. OBJECTIVE: To perform a direct, paired comparison between the water and the nutrient drink test in normal volunteers. METHODS: Thirty eight normal volunteers (19 males, 19 females, mean age 24.4 ± 0.4 years) underwent drink test with water and nutrient (Nutridrink) within 7-10 days. Both tests included a loading (consumption of 100 mL/min for water and 15 mL/min for Nutridrink for the longest possible period of time) and a recuperation phase (observation after cessation of fluid intake), being separated by the maximal saturation point. During phases, satiety, fullness, discomfort, bloating, belching, nausea, pain and burning sensation (epigastric and thoracic) were recorded using a 0-100 visual analogue scale score (VAS). For the purpose of configuration, four variables were considered: time (t), VAS score (V), VAS slope (S) for a given time period, and probability of participation (Q) at a given timepoint. RESULTS: The loading phase lasted for 11.6 ± 1.7 min in water (total VAS: 879 ± 123, total VAS slope 72.6 ± 10.9 min-1) and 93.3 ± 18.4 min in Nutridrink test (total VAS: 1462 ± 411, total VAS slope 15.9 ± 3.2 min-1); P<0.001. The mean ingested volume recorded was 1155 ± 164 mL for water and 1399 ± 276 mL for nutrient; P = 0.076. Cessation of fluid intake was mainly attributed to fullness (76.3%) in water and satiety (69.2%) in Nutridrink test. Nausea was recorded only in Nutridrink test (15.4%). No volunteer reported substantial, persistent pain or burning sensation. The recuperation phase lasted 63.6 ± 7.8 min in water (total VAS: 278 ± 75, total VAS slope 3.97 ± 0.95 min-1) and 123.2 ± 17.5 min in Nutridrink test (total VAS: 841 ± 126, total VAS slope 6.81 ± 1.63 min-1); P<0.001. Concerning total VAS scores for both phases of the two tests, fullness and satiety represented a mere four fifths of the total (43% and 36%, respectively). Belching (8%), bloating (6%), nausea (4%), and discomfort (3%) followed, while pain and burning sensation represented <1% of the whole. However, intra- and intertest correlations concerning total and symptom-specific VAS scores revealed statistically significant variations underlying differences in physiology of liquid intake. A multiple regression model considering body mass index, gender and age as dependent variables, and total and symptom-specific VAS scores and slopes for both phases of the two tests as independent variables, did not reveal any primary correlation. The function linking the expected probability of participation Q and symptom-specific VAS score V with time t is approached by the formulas Q(t)=1/[1+(t/c)&#094;k] and V(t)=V0*e&#094;(-t/c), respectively; V0 is the mean symptom-specific VAS score, c, and k are phase- and test- related constants, and e = 2.718 is the base of natural logarithms. CONCLUSION: The comparative standardization of both drink tests in normal individuals might provide a tool for clinical application, targeting the diagnosis and treatment of relevant functional disorders

Diagnosis and outcome of oesophageal Crohn's disease

Abstract BACKGROUND AND AIMS: Crohn's disease (CD) can involve any part of the gastrointestinal tract. We aimed to characterize clinical, endoscopic, histologic features and treatment outcomes of CD patients with oesophageal involvement. METHODS: We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. RESULTS: A total of 40 patients were reported [22 males, mean (\ub1SD, range) age at oesophageal CD diagnosis: 25 (\ub113.3, 10-71) years and mean time of follow-up: 67 (\ub168.1, 3-240) months]. Oesophageal involvement was established at CD diagnosis in 26 patients (65%) and during follow-up in 14. CD was exclusively located in the oesophagus in 2 patients. Thirteen patients (32.2%) were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in 5 patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors (PPIs) were administered in 37 patients (92.5%). Three patients underwent endoscopic dilation for symptomatic strictures and none oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients (82.5%) after a mean time of 7 (\ub15.6, 1-18) months. Follow-up endoscopy was performed in 29/40 patients and 26/29 (89.7%) achieved mucosal healing. CONCLUSION: In this case series the endoscopic and histologic characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing IBD-related therapy occurring in two thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients

Diagnosis and management of iatrogenic endoscopic perforations: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement - Update 2020

ESGE recommends that each center implements a written policy regarding the management of iatrogenic perforations, including the definition of procedures that carry a higher risk of this complication. This policy should be shared with the radiologists and surgeons at each center. 2 ESGE recommends that in the case of an endoscopically identified perforation, the endoscopist reports its size and location, with an image, and statement of the endoscopic treatment that has been applied. 3 ESGE recommends that symptoms or signs suggestive of iatrogenic perforation after an endoscopic procedure should be rapidly and carefully evaluated and documented with a computed tomography (CT) scan. 4 ESGE recommends that endoscopic closure should be considered depending on the type of the iatrogenic perforation, its size, and the endoscopist expertise available at the center. Switch to carbon dioxide (CO2) endoscopic insufflation, diversion of digestive luminal content, and decompression of tension pneumoperitoneum or pneumothorax should also be performed. 5 ESGE recommends that after endoscopic closure of an iatrogenic perforation, further management should be based on the estimated success of the endoscopic closure and on the general clinical condition of the patient. In the case of no or failed endoscopic closure of an iatrogenic perforation, and in patients whose clinical condition is deteriorating, hospitalization and surgical consultation are recommended

Humoral and In Vivo Cellular Immunity against the Raw Insect-Derived Recombinant Leishmania infantum Antigens KMPII, TRYP, LACK, and papLe22 in Dogs from an Endemic Area

Leishmania infantum causes visceral leishmaniasis, a severe zoonotic and systemic disease that is fatal if left untreated. Identification of the antigens involved in Leishmania-specific protective immune response is a research priority for the development of effective control measures. For this purpose, we evaluated, in 27 dogs from an enzootic zone, specific humoral and cellular immune response by delayed-type hypersensitivity (DTH) skin test both against total L. infantum antigen and the raw Trichoplusia ni insect-derived kinetoplastid membrane protein-11 (rKMPII), tryparedoxin peroxidase (rTRYP), Leishmania homologue of receptors for activated C kinase (rLACK), and 22-kDa potentially aggravating protein of Leishmania (rpapLe22) antigens from this parasite. rTRYP induced the highest number of positive DTH responses (55% of leishmanin skin test [LST]-positive dogs), showing that TRYP antigen is an important T cell immunogen, and it could be a promising vaccine candidate against this disease. When TRYP-DTH and KMPII-DTH tests were evaluated in parallel, 82% of LST-positive dogs were detected, suggesting that both antigens could be considered as components of a standardized DTH immunodiagnostic tool for dogs