Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013-2022: Data from the European Registry on H. pylori Management (Hp-EuReg).

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

Cardiovascular risk factors in coeliac disease (ARCTIC): a protocol of multicentre series of studies.

INTRODUCTION: There is only limited and controversial information available on the cardiovascular (CV) risk in coeliac disease (CD). In this study, we plan to investigate the body composition and CV risk-related metabolic parameters at the diagnosis of CD and on a gluten-free diet in a Hungarian cohort of patients with CD. METHODS AND ANALYSIS: This study consists of two case-control studies and a prospective cohort study, involving newly diagnosed and treated patients with CD with age and sex-matched non-CD control subjects with an allocation ratio of 1:1. CD-related symptoms, quality of life, quality of the diet and CV risk will be assessed with questionnaires. Our primary outcomes are body composition parameters, which will be estimated with InBody 770 device. Secondary outcomes are CV-risk related metabolic parameters (eg, serum lipids, haemoglobin A1c, homeostatic model assessment index, liver enzymes, homocysteine, interleukin 6, galectin-3) and enteral hormones (leptin, ghrelin, adiponectin) measured from venous blood samples for all participants. Fatty liver disease will be assessed by transabdominal ultrasonography. In statistical analysis, descriptive and comparative statistics will be performed. With this study, we aim to draw attention to the often neglected metabolic and CV aspect of the management of CD. Findings may help to identify parameters to be optimised and reassessed during follow-up in patients with CD. ETHICS AND DISSEMINATION: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05530070.

[The most common gastrointestinal alterations in patients with post-COVID syndrome]. / A poszt-COVID-szindrómával diagnosztizált betegek leggyakoribb gastrointestinalis eltérései.

INTRODUCTION: Post-COVID syndrome may affect the gastrointestinal tract. However, risk factors of post-COVID syndrome are still unknown. OBJECTIVE: We aimed to identify the most common gastrointestinal symptoms, abnormal laboratory findings and risk factors relevant to post-COVID syndrome. METHOD: In this retrospective study, we included 79 patients admitted to Semmelweis University Department of Surgery, Transplantation and Gastroenterology between October 2020 and September 2022. We investigated clinical data, laboratory findings and determined the major risk factors. RESULTS: Most of the patients were women (46/79), their mean age was 47.6 years and patients were overweight (BMI: 26.3 kg/m2). The most common comorbidities were cardiovascular diseases (21/79), hypertension (20/79), diabetes (11/79) and malignant diseases (9/79). Typical indications for gastroscopy were dyspepsia (16/79) and epigastric pain (10/79). The most common indications for colonoscopy were diarrhea (29/79) and weight loss (28/79). Among abnormal laboratory findings, liver enzymes levels (GOT: 83.5 U/L, GPT: 85 U/L, GGT: 70 U/L) and ferritin (351.5 ng/mL) were higher in post-COVID patients. Typical conditions diagnosed by gastroscopy, colonoscopy and abdominal ultrasound were gastroesophageal reflux disease (11/26), irritable bowel syndrome (2/19) and diffuse hepatic lesions, respectively. The number of unvaccinated patients was higher compared to those receiving any COVID-19 vaccines (58% vs. 29%). Of the vaccinated patients, 12 patients received mRNA vaccines (10 Pfizer-BioNTech, 2 Moderna) and 6 patients received viral vector vaccines (2 AstraZeneca, 4 Sputnik V). CONCLUSION: We identified female gender, obesity, cardiovascular diseases, cancer, hypertension and diabetes as major risk factors of post-COVID syndrome. Vaccinated status may prevent post-COVID gastrointestinal symptoms. Orv Hetil. 2023; 164(31): 1206-1212.

[Comparison of outcome of rigid and self-expanding stents for palliation of malignant dysphagia]. / A malignus eredetu dysphagia palliatív kezelésére használt merev és öntáguló sztentek eredményeinek összehasonlító vizsgálata.

INTRODUCTION: Between 1984 and 2019, 1005 rigid prostheses and 423 self-expanding stents were inserted for palliation of malignant esophageal stenosis. OBJECTIVE: The aim of this study was the comparison of the treatment results using the two types of prosthesis. METHOD: Retrospective analysis has been performed comparing the characteristics and treatment results of the two patients groups referring to the technical success of the procedures, procedure-related complications, change in the quality of life, and survival time. RESULTS: A comparison of average ages, duration time of dysphagia, quantity of weight loss, and the progress of the malignancy proves that palliation with self-expanding stents made it possible to treat more patients in worse condition. The number of complications in the patient group treated with stents was significantly higher at 29.3%/20.9%. Endoscopic intervention was performed to treat complications in 68.6% of cases with rigid prostheses and in 53.2% of patients treated with stents. Relevant improvement of dysphagia and the patients' quality of life was observed in 97% of those who were treated with a rigid prosthesis and in 91.3% of those who were treated with self-expanding stents. The survival time in the group of patients treated with stents was significantly shorter by 4.3/5.4 months than in the other group. CONCLUSION: The use of self-expanding stents in palliative treatment of malignant strictures have brought significant changes in everyday practice with increasing the possibilities. The treatment results were not improved by their application as much as the worse condition of the patient group worsened them. Orv Hetil. 2022; 163(49): 1952-1961.

The Elevated De Ritis Ratio on Admission Is Independently Associated with Mortality in COVID-19 Patients.

Liver damage in COVID-19 patients was documented as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or an elevated AST/ALT ratio, known as the De Ritis ratio. However, the prognostic value of the elevated De Ritis ratio in COVID-19 patients is still unknown. The aim of our study was to evaluate the prognostic value of the De Ritis ratio compared to other abnormal laboratory parameters and its relation to mortality. We selected 322 COVID-19 patients in this retrospective study conducted between November 2020 and March 2021. The laboratory parameters were measured on admission and followed till patient discharge or death. Of the 322 COVID-19 patients, 57 (17.7%) had gastrointestinal symptoms on admission. The multivariate analysis showed that the De Ritis ratio was an independent risk factor for mortality, with an OR of 29.967 (95% CI 5.266-170.514). In ROC analysis, the AUC value of the the De Ritis ratio was 0.85 (95% CI 0.777-0.923, p < 0.05) with sensitivity and specificity of 80.6% and 75.2%, respectively. A De Ritis ratio ≥1.218 was significantly associated with patient mortality, disease severity, higher AST and IL-6 levels, and a lower ALT level. An elevated De Ritis ratio on admission is independently associated with mortality in COVID-19 patients, indicating liver injury and cytokine release syndrome.

First record of the brown marmorated stink bug, Halyomorpha halys (Hemiptera: Heteroptera: Pentatomidae), in Hungary, with description of the genitalia of both sexes.

The brown marmorated stink bug, Halyomorpha halys (Stål, 1855) (Hemiptera: Heteroptera: Pentatomidae) is recorded for the first time from Hungary. The circumstances of finding this species and a detailed description of both male and female genitalia are given. The currently known distribution, biology and significance of the species are briefly reviewed.

Expansion of hepatic stem cell compartment boosts liver regeneration.

The hepatic stem cells reside periportally forming the canals of Hering in normal liver. They can be identified by their unique immunophenotype in rat. The oval cells, the progenies of stem cells invade deep the liver parenchyma after activation and differentiate into focally arranged small-and eventually trabecularly ordered regular hepatocytes. We have observed that upon the completion of intense oval cell reactions narrow ductular structures are present in the parenchyma, we propose to call them parenchymal ductules. These parenchymal ductules have the same immunophenotype [cytokeratin (CK)7-/CK19+/alpha-fetoprotein (AFP)-/delta-like protein (DLK)-] as the resting stem cells of the canals of Hering, but different from them reside scattered in the parenchyma. In our present experiments, we have investigated in an in vivo functional assay if the presence of these parenchymal ductules has any impact on a progenitor cell driven regeneration process. Parenchymal ductules were induced either by an established model of oval cell induction consisting of the administration of necrogenic dose of carbontetrachloride to 2-acetaminofluorene pretreated rats (AAF/CCl4) or a large necrogenic dose of diethylnitrosamine (DEN). The oval cells expanded faster and the foci evolved earlier after repeated injury in the livers with preexistent parenchymal ductules. When the animals were left to survive for one more year increased liver tumor formation was observed exclusively in the DEN treated rats. Thus, repeated oval cell reactions are not necessarily carcinogenic. We conclude that the expansion of hepatic stem cell compartment conceptually can be used to facilitate liver regeneration without an increased risk of tumorigenesis.

Structural analysis of oval-cell-mediated liver regeneration in rats.

UNLABELLED: We have analyzed the architectural aspects of progenitor-cell-driven regenerative growth in rat liver by applying the 2-acetaminofluorene/partial hepatectomy experimental model. The regeneration is initiated by the proliferation of so-called oval cells. The oval cells at the proximal tips of the ductules have a more differentiated phenotype and higher proliferative rate. This preferential growth results in the formation of a seemingly random collection of small hepatocytes, called foci. These foci have no clonal origin, but possess a highly organized structure, which shows similarities to normal hepatic parenchyma. Therefore, they can easily remodel into the lobular structure. Eventually, the regenerated liver is constructed by enlarged hepatic lobules; no new lobules are formed during this process. The foci of the Solt-Farber experimental hepatocarcinogenesis model have identical morphological features; accordingly, they also represent only regenerative, not neoplastic, growth. CONCLUSION: Progenitor-cell-driven liver regeneration is a well-designed, highly organized tissue reaction, and better comprehension of the architectural events may help us to recognize this process and understand its role in physiological and pathological reactions.

Development of arterial blood supply in experimental liver metastases.

In this study, we present a mechanism for the development of arterial blood supply in experimental liver metastases. To analyze the arterialization process of experimental liver metastases, we elucidated a few key questions regarding the blood supply of hepatic lobules in mice. The microvasculature of the mouse liver is characterized by numerous arterioportal anastomoses and arterial terminations at the base of the lobules. These terminations supply one hepatic microcirculatory subunit per lobule, which we call an arterial hepatic microcirculatory subunit (aHMS). The process of arterialization can be divided into the following steps: 1) distortion of the aHMS by metastasis; 2) initial fusion of the sinusoids of the aHMS at the tumor parenchyma interface; 3) fusion of the sinusoids located at the base of the aHMSs, which leads to the disruption of the vascular sphincter (burst pipe); 4) incorporation of the dilated artery and the fused sinusoids into the tumor; and 5) further development of the tumor vasculature (arterial tree) by proliferation, remodeling, and continuous incorporation of fused sinusoids at the tumor-parenchyma interface. This process leads to the inevitable arterialization of liver metastases above the 2000- to 2500-mum size, regardless of the origin and growth pattern of the tumor.

Architectural and immunohistochemical characterization of biliary ductules in normal human liver.

The canals of Hering or biliary ductules have been described to connect the bile canaliculi with the interlobular bile ducts, and thus forming the distal part of the biliary tree. Studies in the last two decades suggested that the cells constructing these ductules could behave as hepatic progenitor cells. The canals of Hering are confined to the periportal space in the rat, while they have been reported to spread beyond the limiting plate in human liver. The distribution of the distal biliary ductules in normal human hepatic tissue has been investigated in our recent experiments. We could demonstrate the presence of interlobular connective tissue septa in a rudimentary form in healthy livers. The canals of Hering run in these septa in line with the terminal branches of the portal vein and hepatic arteries. This arrangement develops in the postnatal period but regresses after early childhood. The canals of Hering can be identified by the unique epithelial membrane antigen (EMA)-/CD56+/CD133+ immunophenotype. The canals of Hering leave the periportal space and spread into the liver parenchyma along rudimentary interlobular septa outlining the hepatic lobules. Our observations refine the original architectural description of the intraparenchymal portion of the canals of Hering in the human liver. The distinct immunophenotype supports their unique biological function.

Architectural changes during regenerative and ontogenic liver growth in the rat.

Although liver architecture has a major impact on function, morphological aspects of liver growth are relatively neglected. In our recent experiments, the architectural changes of the rat liver were compared during 2 basic processes: ontogeny and regenerative liver growth. The hepatic tissue is constructed as structural/functional units, and probably the most established and well-defined such unit is the classic lobule. The extent and orientation of the lobules are variable in the liver, and this renders their accurate size determination more difficult. The filling of the liver vasculature by a colored resin nicely outlined the surface lobules, enabling an analysis of the alterations of these structures during liver growth. There are 3 structural components of postnatal physiological liver development: enlargement of the hepatocytes and expansion and multiplication of the liver lobules. However, the enlargement of the lobules is exclusively responsible for the regenerative liver growth following partial hepatectomy. The number of hepatic lobules does not change during this latter reaction, but they gain a more complex, irregular structure.

Triiodothyronine accelerates differentiation of rat liver progenitor cells into hepatocytes.

The 2-acetaminofluorene/partial hepatectomy (AAF/Phx) model is widely used to induce oval/progenitor cell proliferation in the rat liver. We have used this model to study the impact of a primary hepatocyte mitogen, triiodothyronine (T3) on the liver regenerating by the recruitment of oval/progenitor cells. Administration of T3 transiently accelerates the proliferation of the oval cells, which is followed by rapid differentiation into small hepatocytes. The oval cell origin of the small hepatocytes has been proven by tracing retrovirally transduced and BrdU marked oval cells. The differentiating oval cells become positive for hepatocyte nuclear factor-4 and start to express hepatocyte specific connexin 32, alpha1 integrin, Prox1, cytochrom P450s, and form CD 26 positive bile canaliculi. At the same time oval cell specific OV-6 and alpha-fetoprotein expression is lost. The upregulation of hepatocyte specific mRNAs: albumin, tyrosine aminotransferase and tryptophan 2,3-dioxygenase detected by real-time PCR also proves hepatocytic maturation. The hepatocytic conversion of oval cells occurs on the seventh day after the Phx in this model while the first small hepatocytes appear 5 days later without T3 treatment. The administration of the primary hepatocyte mitogen T3 accelerates the differentiation of hepatic progenitor cells into hepatocytes in vivo, and that may have therapeutic potential.