Background: Hypercalcemia is a rare etiology of acute pancreatitis; only a few cases have been reported in the literature, and the severity of hypercalcemia-induced AP is unknown. We aimed to assess the occurrence and severity of hypercalcemia-induced AP and compare it with the clinical characteristics of AP caused by other etiological factors. Methods: We collected data from patients from the Hungarian Acute Pancreatitis Registry who had AP, a serum calcium level above 2.6 mmol/L, and no other AP etiology. AP patients with etiologies other than hypercalcemia served as control. Results: A total of 1.20% of our AP patients (16/1328) had a clear hypercalcemic etiology, 5.05% (67/1328) had a mixed etiology, and 1245 patients were in the control group. Severe AP, organ failure, and renal failure were significantly more common in patients with hypercalcemia-induced AP than in the control or the mixed etiology groups. Heart failure was significantly more frequent in the clear hypercalcemia-induced group than in patients with normal serum calcium AP. Respiratory failure was significantly more common in the clear hypercalcemia-induced AP group than in the mixed etiology-induced group. There was no significant difference in other analyzed parameters. The outcome of AP was not associated with the severity of hypercalcemia within the hypercalcemic group. Conclusions: Compared with AP of different etiologies, hypercalcemia-induced AP is more likely to develop into severe AP and organ failure (heart and kidneys).

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients’ care.

INTRODUCTION:The outcomes of surgical interventions for achalasia treatment improved with the advent of minimally invasive surgery. Robotic-assisted Heller-Dor's (RAHD) procedure established over the last years, provides important advantages to surgeons, such as binocular three-dimensional vision and improvement of fine motor control.METHOD:Between October and December of 2022, first in Hungary, 3 patients (37-year-old man, 55- and 72-year-old women) underwent RAHD procedure for achalasia at the Clinical Centre of the University of Pécs using the da Vinci Xi system.RESULTS:RAHD procedure was feasible without any particular problems and the postoperative course of all three patients was uneventful. The operation times were 198, 204 and 238 minutes, including 23, 19 and 14 minutes for the setup time of the robot. By the last patient, due to an accompanying hiatal hernia, an additional hiatal reconstruction was also performed. In the first 2 cases, the patients were discharged on the 4th postoperative day, while in the last case, with the additional hiatal reconstruction, the patient was emitted on the 6th postoperative day.DISCUSSION:There are several published studies about RAHD cardiomyotomy. The general conclusion is that, in experienced hands, RAHD procedure is easy to perform, ensures a meticulous esophageal and gastric myotomy, allowing to visualize and divide each muscle fiber with a significantly lower rate of mucosal perforations. However, by RAHD procedure, the overall costs are higher, including a longer operation time during the learning curve. At the same time, the avoidance of mucosal lacerations and their possible consequences has to be weighed against the higher overall costs.CONCLUSION:Laparoscopic cardiomyotomy is the first standard upper-gastrointestinal operation where a clear advantage of the use of a surgical robot has been proven. Thus, wherever this equipment is available, it should be preferred for this procedure. Orv Hetil. 2023; 164(14): 542-547.

Bevezetés: Az achalasia miatt végzett sebészeti beavatkozások eredményei jelentősen javultak a minimálisan invazív sebészet bevezetésével. A robotasszisztált Heller–Dor (RAHD)-műtét az utóbbi évek során kezd elterjedni, mivel olyan előnyöket biztosít a sebész számára, mint a háromdimenziós látás és a műtét alatti finommozgások még magasabb szintű kontrollja. Módszer: 2022. október 1. és december 31. között, Magyarországon először, a Pécsi Tudományegyetem Klinikai Központjában 3 betegen (37 éves férfi és 55, illetve 72 éves nő) végeztünk achalasia miatt RAHD-műtétet a da Vinci Xi rendszer segítségével. Eredmények: Mindhárom esetben szövődménymentes RAHD-műtét történt, és a betegek a műtét után panaszmentessé váltak. A műtéti idő 198, 204 és 238 perc volt, mely magában foglalta a 23, 19 és 14 perces dokkolási időt. Az utolsó betegnél hiatus hernia is ismert volt, ezért egy időben ennek rekonstrukcióját is elvégeztük. Az első 2 beteget a műtétet követő negyedik, a hiatusrekonstrukción is átesett 3. beteget a műtét utáni 6. napon engedtük otthonába. Megbeszélés: Az utóbbi években egyre több vizsgálat ismert, mely a RAHD-cardiomyotomiával foglalkozik. Általánosságban azt a következtetést vonják le, hogy gyakorlott kézben ez könnyen elvégezhető műtét, mely nagyon alapos myotomiát biztosít mind a nyelőcső, mind a gyomor területén azáltal, hogy nagy nagyításban minden izomrost felismerhető, és ennek köszönhetően lényegesen kevesebb perforáció fordul elő a műtét során a laparoszkópos műtétekhez viszonyítva. Ugyanakkor az is ismert, hogy költségesebb beavatkozás, amelyet a tanulási időszak hosszabb műtéti ideje is tovább drágít. A nyálkahártya-sérülések és a következményes szövődmények elkerülése azonban ellensúlyozhatja hosszú távon ezeket a magasabb költségeket. Következtetés: A laparoszkópos cardiomyotomia az egyik olyan felső gastrointestinalis standard műtét, amelynél a robot haszna egyértelműen bizonyítható. Ezért azon helyeken, ahol a robotsebészeti rendszer hozzáférhető, javasolt ezt a beavatkozást azzal végezni. Orv Hetil. 2023; 164(14): 542–547.

Introduction: Dyspeptic symptoms are frequent in the general population, with a high socioeconomic burden. Helicobacter pylori (H. pylori) might be a possible etiological factor; however, it is also common in H. pylori negative gastritis. Clarification of the underlying aetiology might be beneficial to set up the optimal treatment strategy for dyspepsia and chronic gastritis (CG) itself. We aimed to assess the prevalence of dyspeptic symptoms in patients with H. pylori negative CG and explore autoimmunity's possible role.Methods: This retrospective study included data from patients with H. pylori negative CG. Exclusion criteria were (1) acute gastritis; (2) reactive gastropathy; (3) subjects without any serology testing results; (4) H. pylori positivity; (5) presence of atrophy, intestinal metaplasia (IM), gastroesophageal reflux disease (GERD), ulcer, or cancer. The following endpoints were assessed (1) the rate of dyspepsia-like symptoms; (2) association between dyspepsia and autoimmune disease-related seromarker positivity (AISP); (3) frequency of other symptoms in CG and its association with AISP; (4) location of the inflammation and its association with AISP.Results: From a total of 285 patients, 175 were included in this study. Among these patients, 95 experienced dyspeptic symptoms (54.29%) and were associated more with AISP (p = 0.012), especially with celiac seropositivity (p = 0.045), anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) positivity (p = 0.043). A significant association was not found with other tested autoimmune (AI)-related antibody positivity.Conclusion: Positivity of seromarkers of autoimmune diseases in chronic gastritis may predispose to have dyspeptic symptoms and may be the causative factor behind some cases of uninvestigated dyspepsia. These data suggest that further prospective studies are needed to clarify whether screening for autoantibodies in patients with dyspepsia is cost-effective and helps the earlier diagnosis of autoimmune diseases.

AbstractBackgroundAcute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed.MethodsThe early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit‐learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross‐validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross‐validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP).ResultsThe prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy‐to‐use web application in the Streamlit Python‐based framework (http://easy‐app.org/).ConclusionsThe EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.

Background and Aims: The underlying aetiology of chronic gastritis (CG) often remains unknown due to its underrated significance in clinical practice. However, the role of chronic inflammation of the stomach in the development of atrophy, intestinal metaplasia (IM) and eventually of gastric cancer is well documented. We aimed to explore the possible aetiological factors of CG, determine the prevalence of systemic autoimmune disorders in patients with CG of unknown aetiology, and clarify the role of autoantibodies in the development of precancerous lesions in the stomach. Methods: This is a retrospective, cross-sectional study, conducted from January 2016 to January 2020, including data from 175 patients with CG. Exclusion criteria were: (1) acute gastritis; (2) reactive gastropathy; (3) gastric cancer; (4) subjects without any serology testing results; and (5) Helicobacter pylori positivity. The primary endpoint was a composite endpoint involving gastric atrophy and IM. Results: Fifty-five per cent of patients with CG had autoantibodies. Systemic lupus erythematosus (SLE)-related antibodies were positive in most of the cases, including antinuclear antibody (ANA) positivity, which was found in 19.13% of the patients. Autoimmune positivity was shown to be associated with precancerous lesions in the stomach (p<0.001): IM, atrophy and IM with atrophy. Anti-parietal cell antibody positivity seems to be a significant risk factor for IM and IM with atrophy. Autoimmune thyroiditis-related antibodies and ANA positivity by itself were only associated with atrophy; SLE-related antibodies and inflammatory bowel diseases related antibodies (ASCA and ANCA) correlated either with IM or with atrophy. No significant relation was found between any other investigated autoimmune disease-related antibodies and precancerous lesions. Conclusions: Autoimmune positivity often underlies gastritis of unknown aetiology and predisposes to precancerous lesions in the stomach. These antibodies can serve as non-invasive markers for the of optimal timing of an endoscopic follow-up strategy. Furthermore, CG can be an early symptom of a systemic autoimmune disorder.

Background: Metabolic risk factors, such as obesity, hypertension, and hyperlipidemia are independent risk factors for the development of various complications in acute pancreatitis (AP). Hypertriglyceridemia dose-dependently elicits pancreatotoxicity and worsens the outcomes of AP. The role of hyperglycemia, as a toxic metabolic factor in the clinical course of AP, has not been examined yet. Methods: We analyzed a prospective, international cohort of 2250 AP patients, examining associations between (1) glycosylated hemoglobin (HbA1c), (2) on-admission glucose, (3) peak in-hospital glucose and clinically important outcomes (mortality, severity, complications, length of hospitalization (LOH), maximal C-reactive protein (CRP)). We conducted a binary logistic regression accounting for age, gender, etiology, diabetes, and our examined variables. Receiver Operating Characteristic Curve (ROC) was applied to detect the diagnostic accuracy of the three variables. Results: Both on-admission and peak serum glucose are independently associated with AP severity and mortality, accounting for age, gender, known diabetes and AP etiology. They show a dose-dependent association with severity (p < 0.001 in both), mortality (p < 0.001), LOH (p < 0.001), maximal CRP (p < 0.001), systemic (p < 0.001) and local complications (p < 0.001). Patients with peak glucose >7 mmol/l had a 15 times higher odds for severe AP and a five times higher odds for mortality. We found a trend of increasing HbA1c with increasing LOH (p < 0.001), severity and local complications. Conclusions: On-admission and peak in-hospital glucose are independently and dose-dependently associated with increasing AP severity and mortality. In-hospital laboratory control of glucose and adequate treatment of hyperglycemia are crucial in the management of AP. (c) 2021 Published by Elsevier B.V. on behalf of IAP and EPC.

Background: Gastric cancer is one of the most common cancers worldwide, with a high mortality rate. The potential etiological role of autoimmune (AI) disorders has been described in gastric cancer; however, the literature is controversial. This study aims to provide a comprehensive summary of the association between autoimmune disorders and the incidence of gastric cancer.Methods: This study was registered on PROSPERO under registration number CRD42021262875. The systematic literature search was conducted in four scientific databases up to May 17, 2021. Studies that reported standardized incidence rate (SIR) of gastric cancer in autoimmune disorders were eligible. We calculated pooled SIRs with 95% confidence intervals (CIs) in this meta-analysis.Results: We included 43 articles describing 36 AI disorders with data of 499,427 patients from four continents in our systematic review and meta-analysis. Significantly increased incidence of gastric cancer was observed in dermatomyositis (SIR = 3.71; CI: 2.04, 6.75), pernicious anemia (SIR = 3.28; CI: 2.71, 3.96), inflammatory myopathies (SIR = 2.68; CI:1.40; 5.12), systemic lupus erythematosus (SIR = 1.48; CI: 1.09, 2.01), diabetes mellitus type I (SIR = 1.29; CI:1.14, 1,47), and Graves' disease (SIR = 1.28; CI: 1.16, 1.41). No significant associations could be found regarding other AI disorders.Conclusions: Pernicious anemia, Graves' disease, dermatomyositis, diabetes mellitus type I, inflammatory myopathies, and systemic lupus erythematosus are associated with higher incidence rates of gastric cancer. Therefore, close gastroenterological follow-up or routinely performed gastroscopy and application of other diagnostic measures may be cost-effective and clinically helpful for patients diagnosed with these autoimmune diseases.

Background: Effective and selective oral rinses are required in the daily medical and dental practice. Currently mouthwashes used have substantial side effects. Objectives: Our aim was to evaluate the efficacy of chlorine dioxide-containing mouthwashes in comparison with other previously established mouth rinses in healthy adults using oral hygiene indices. Methods: This work was registered in PROSPERO (CRD42018099059) and carried out using multiple databases and reported according to the PRISMA statement. The search terms used were “chlorine dioxide” AND “oral”, and only randomised controlled trials (RCTs) were included. The primary outcome was the alteration of the plaque index (PI), while the secondary outcomes were the gingival index (GI) and bacterial counts. For the risk of bias assessment, the Cochrane Risk of Bias Tool was used. Statistical analysis for data heterogeneity was performed by Q-value and I2-tests. Results: 364 articles were found in the databases. After the selection process, only five RCTs were eligible for meta-analysis. Data heterogeneity was low. There were no statistical differences in effectiveness between chlorine dioxide and other effective mouth rinses in PI (0.720±0.119 vs 0.745±0.131; 95%; confidence intervals (CIs): 0.487-0.952 vs 0.489-1.001, respectively) and GI (0.712±0.130 vs 0.745±0.131; 95% CIs: 0.457–0.967 vs 0.489– 1.001, respectively) and also in bacterial counts. Conclusion: Chlorine dioxide reduces both plaque and gingival indices and bacterial counts in the oral cavity similar to other routinely used oral rinses, however, the evidence supporting this outcome is very limited. Therefore, further large scale RCTs are needed to decrease the risk of bias.

There is scarce information on the prevalence of irritable bowel syndrome (IBS) in East Europe. Most countries have small, local studies or studies that to our knowledge are not published in internationally available journals. This is a report from the NeurogastRO 2019 meeting held in Ia.i, Romania, 7-9 November 2019. During the meeting, specialists from 12 East and Central European countries presented data on IBS epidemiology in their countries. We report the stage of knowledge in each of these countries.

The main causes of acute pancreatitis (AP) are biliary disease, alcohol consumption, hypertriglyceridaemia (HTG) and endoscopic retrograde cholangiopancreatography (ERCP). The aim of this meta-analysis was to evaluate the effects of these aetiological factors on the severity and outcome of AP. Pubmed and Embase were searched between 01/01/2012 and 31/05/2020. Included articles involved adult alcoholic, biliary, HTG- or post-ERCP AP (PAP) patients. Primary outcome was severity, secondary outcomes were organ failures, intensive care unit admission, recurrence rate, pancreatic necrosis, mortality, length of hospital stay, pseudocyst, fluid collection and systematic inflammatory response syndrome. Data were analysed from 127 eligible studies. The risk for non-mild (moderately severe and severe) condition was the highest in HTG-induced AP (HTG-AP) followed by alcoholic AP (AAP), biliary AP (BAP) and PAP. Recurrence rate was significantly lower among BAP vs. HTG-AP or AAP patients (OR = 2.69 and 2.98, 95% CI 1.55–4.65 and 2.22–4.01, respectively). Mortality rate was significantly greater in HTG-AP vs. AAP or BAP (OR = 1.72 and 1.50, 95% CI 1.04–2.84 and 0.96–2.35, respectively), pancreatic necrosis occurred more frequently in AAP than BAP patients (OR = 1.58, 95% CI 1.08–2.30). Overall, there is a potential association between aetiology and the development and course of AP. HTG-AP is associated with the highest number of complications. Furthermore, AAP is likely to be more severe than BAP or PAP. Greater emphasis should be placed on determining aetiology on admission.

Background Lactose intolerance is a frequent gastrointestinal disease affecting 47% of the Eastern European population. Small intestinal bacterial overgrowth (SIBO) leads to carbohydrate malabsorption and therefore to false results during lactose breath and tolerance tests. Objectives We aimed to assess the prevalence of lactose maldigestion and intolerance in Hungary and to investigate the role of combined diagnostic method and testing for SIBO in reducing false results. Methods We retrospectively analyzed data from 264 adult symptomatic patients who underwent 50g lactose breath and tolerance tests in parallel over a one-year period at our center. A ≥20 ppm elevation of H2 or less than 1.1 mmol/l rise of blood glucose was diagnostic for lactose maldigestion. Patients with maldigestion who had symptoms during the test were defined as lactose intolerant. Patients with an early (≤90 min) significant (≥20 ppm) rise of H2 during lactose and/or lactulose breath tests were determined to have SIBO. Patients with slow/rapid oro-cecal transit and inappropriate preparation before the test were excluded. Results 49.6% of the 264 patients had lactose maldigestion, and 29.5% had lactose intolerance. The most frequent symptom was bloating (22.7%), while 34.8% of the study population and 60% of the symptomatic patients had SIBO. In 9.1% and 9.8% of the patients, the lactose breath and tolerance test alone gave false positive result compared with the combined method. SIBO was present in 75% of the false positives diagnosed with breath test only. Conclusions The prevalence of lactose intolerance is lower in Hungary compared to the Eastern European value (29.5% vs 47%), so it is worth performing a population-based prospective analysis in this area. A combination of lactose breath and tolerance tests and the careful monitoring of results (with early H2 rise, lactulose breath test, etc.) can decrease the false cases caused by e.g. SIBO.

Background: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. Methods: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (< 1.7 mmol/l, 1.7-2.19 mmol/l, 2.2-5.59 mmol/l, 5.6-11.29 mmol/l, 11.3-22.59 mmol/l, >= 22.6 mmol/l). Results: Hypertriglyceridemia (>= 1.7 mmol/l) presented in 30.6% of the patients and was significantly and dose-dependently associated with younger age and male gender. In 7.7% of AP cases, hypertriglyceridemia was considered as a causative etiological factor (>= 11.3 mmol/l); however, 43.6% of these cases were associated with other etiologies (alcohol and biliary). Hypertriglyceridemia was significantly and dose-dependently related to obesity and diabetes. The rates of local complications and organ failure and maximum CRP level were significantly and dose-dependently raised by hypertriglyceridemia. Triglyceride above 11.3 mmol/l was linked to a significantly higher incidence of moderately severe AP and longer hospital stay, whereas triglyceride over 22.6 mmol/l was significantly associated with severe AP as well. Conclusion: Hypertriglyceridemia dose-dependently aggravates the severity and related complications of AP. Diagnostic workup for hypertriglyceridemia requires better awareness regardless of the etiology of AP. (C) 2020 IAP and EPC. Published by Elsevier B.V.

Stimulation of cannabinoid CB1 receptors or inhibition of nitric oxide synthase (NOS) in the dorsolateral periaqueductal gray (dlPAG) decreases anxiety-like behavior. Moreover, activation of CB1 receptors attenuates flight responses induced by nitric oxide (NO) donors in the dlPAG, suggesting that endocannabinoids and NO could interact to control defensive responses such as anxiety-like behavior. To test this hypothesis male Wistar rats received intra-dlPAG microinjections of anandamide (AEA) or NO inhibitors and were tested in the elevated plus maze (EPM). Combined administration of low and ineffective doses of AEA and the NO scavenger (c-Ptio), the nNOS inhibitor (NPA) or the soluble guanylate cyclase inhibitor (ODQ) induced anxiolytic-like effects. The CB1 receptor antagonist AM251, but not the GABAA receptor antagonist bicuculline, attenuated the effect induced by AEA + c-Ptio combination. No effect, however, was found when anxiolytic doses of these same drugs were administered together. Combination of higher, ineffective doses of AEA and c-Ptio, NPA or ODQ was again anxiolytic. The effect of the former combination was prevented by low and ineffective doses of the GABAA receptor antagonist bicuculline or the GABA synthesis inhibitor l-allilglycine, suggesting that they depend on GABAA-mediated neurotransmission. AM251 was also able to attenuate this effect, indicating that in the presence of NO inhibition, the resultant anxiolytic-like effect could be due to AEA action on CB1 receptors. The present results suggest that the AEA and nitrergic systems exert a complex functional interaction in the dlPAG to modulate anxiety behavior, probably interfering, in addition to glutamate, also with GABAergic mechanisms.

Background and aims Experimental data suggest that the HLA-DQ2 gene dose has a strong quantitative effect on clinical outcomes and severity of celiac disease (CD). We aimed to conduct a meta-analysis with systematic review to investigate the association between HLA-DQB1*02 gene doses and the characteristics of CD. Methods We searched seven medical databases for studies discussing HLA-DQB1 gene dose in CD and various disease characteristics, such as clinical presentation, histology, age at diagnosis, and comorbidities. Odds ratios (OR, for categorical variables) and weighted mean differences (for age) were calculated to compare patients with a double dose of HLA-DQB1*02 versus those with single and zero doses. Heterogeneity was tested with I2-statistics and explored by study subgroups (children and adults). Results Twenty-four publications were eligible for meta-analysis. Classical CD was more frequent with a double versus single dose of the HLA-DQB1*02 allele (OR = 1.758, 95%CI: 1.148–2.692, I2 = 0.0%). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95%CI: 1.189–3.646, I2 = 0.0% and OR = 3.139, 95%CI: 1.142–8.630, I2 = 0.0% for the comparisons of double versus single and double versus zero dose, respectively). Atrophic histology was more prevalent with a double versus zero dose (OR = 2.626, CI: 1.060–6.505, I2 = 21.3%). We observed no gene dose effect regarding diarrhea, age at diagnosis, the severity of villous atrophy, and the association with type 1 diabetes mellitus. Conclusion A double dose of HLA-DQB1*02 gene seems to predispose patients to developing classical CD and villous atrophy. Risk stratification by HLA-DQB1*02 gene dose requires further clarification due to the limited available evidence.

Background: The Baveno VI Consensus Workshop defined criteria (liver stiffness measured by transient elastography <20 kPa and platelet count >150 x 10(9) cells/L) to identify those patients with compensated advanced chronic liver diseases (cACLD) who are unlikely to have varices needing treatment (VNTs) and can safely avoid variceal screening endoscopy. This meta-analysis aimed to quantify the safety and efficacy of these criteria in suspected cACLD with liver stiffness >10 kPa and in compensated chronic liver diseases (cCLD) irrespective of liver stiffness. Methods: A systematic search was conducted in nine databases for studies discussed cACLD or cCLD and tested Baveno criteria against variceal screening endoscopy. The main safety and efficacy endpoints were missed VNT rate and spared endoscopy rate (SER), respectively; calculated with the random effect model. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated with the hierarchical summary receiver operating characteristic model. For all outcome measures, 95% confidence intervals were computed. Heterogeneity was tested with I-2-statistics. Results: The search yielded 13 studies including 4,464 patients which reported on suspected cACLD. Pooled missed VNT rate was 0.3% (0.1-0.6%; I-2 = 45.5%), pooled SER was 32.8% (24.8-41.4%; I-2 = 97.0%). Sensitivity, specificity, and AUC of Baveno criteria were 97% (95-98%), 41% (27-57%), and 96% (94-97%), respectively. In the subgroups of cACLD from hepatitis C and B viruses, non-alcoholic fatty liver disease/steatohepatitis, or alcohol, missed VNT rates were 0.0% (0.0-0.3%), 1.2% (0.4-2.2%), 0.0% (0.0-1.3%), or 0.0% (0.0-0.4%), while SERs were 24.2% (20.5-28.1%), 24.9% (21.7-28.4%), 38.6% (10.9-70.8%), or 27.0% (16.9-38.4%), respectively. If we expanded the study population to cCLD, 27 studies included 7,534 patients. Missed VNT rate was 0.2% (0.1-0.5%; I-2 = 39.8%) with a SER of 30.5% (25.2-36.2%; I-2 = 96.1%) while Se, Sp, and AUC were 97% (93-99%), 35% (27-44%), and 80% (77-84%), respectively. Conclusions: The application of Baveno criteria significantly reduces the number of unnecessary variceal screening endoscopies while being safe: cACLD patients with liver stiffness <20 kPa and platelet count > 150 x 10(9) cells/L carry a very low chance (i.e., 0.3%) of having VNTs. The criteria preserve low missed VNT rate with lower diagnostic performance among cCLD patients.