MF VSI Bioinformatikos laboratorija (04.06.04)

Introducción: En la CBP, la HPCS puede presentarse incluso en fases precirróticas debido a un componente presinusoidal. Esto puede limitar la precisión de la rigidez hepática (RH) y los criterios de Baveno VII (BVII) para estimar el riesgo de várices esofágicas (VE). Objetivos: Determinar la utilidad de la medición de la RE para predecir la presencia de VE y varices con necesidad de tratamiento (VNT) en pacientes con CBP. Métodos: Estudio transversal en 12 centros de la ERN-Liver. Se incluyeron pacientes con CBP que tenían al menos uno de los siguientes criterios; RH ? 8 kPa, esplenomegalia, plaquetas ? 150 × 109/L o signos ecográficos de cirrosis y/o hipertensión portal. La RH y la RE se determinaron mediante FibroScan. Se recogieron los resultados de analítica, ecografía (± 6 meses respecto a la RE) y endoscopia digestiva (± 12 meses). Resultados: Se incluyeron 126 pacientes, 110 (87%) mujeres, con una mediana de edad 64 (RIQ 58-71) años, 89% (n = 113) tenían RH ? 8 kPa, 48% (n = 61) plaquetopenia, 49% (n = 62) esplenomegalia y 65% (n = 82) cirrosis. Las medianas de RH y RE fueron 13,6 kPa (RIQ 9,1-21,3) y 36,6 kPa (RIQ 25,2-48,6), respectivamente. El 39% (n = 49) de los pacientes tenían VE, de los cuales 28% (n = 14) eran VNT. La frecuencia de VNT fue significativamente mayor en pacientes con RH > 15 kPa (24%) que en aquellos con RH 8-15 kPa (4%) o < 8 kPa (0%; p = 0,002). Los criterios de BVII para descartar HPCS (RH ?15 kPa y plaquetas ? 150 × 109/L), mostraron una precisión moderada con AUC 0,71, sensibilidad (S) 85%, especificidad (E) 55% y falsos negativos (FN) 15%. BVII para confirmar HPCS (RH > 25 kPa) tuvo una capacidad limitada con AUC 0,53, S 20%, E 87% y FN 80%. El mejor punto de corte de la RH para confirmar VE fue 9,8 kPa (AUC 0,73). La RE fue el parámetro con mejor rendimiento diagnóstico (AUC 0,79, S 78%, E 74%, FN 22%). En pacientes con RH ?15 kPa, la RE superó a la RH y a las plaquetas por separado (AUC 0,78 vs. 0,75 y 0,77, respectivamente). La combinación de RE y plaquetas alcanzó la mayor precisión (AUC 0,81; S 47%; E 95%; FN 53%). Para el cribado de VNT, los criterios BVII (RH ? 20 kPa o plaquetas ?150×109/L) mostraron una capacidad predictiva moderada (AUC 0,68; S 86%; E 51%; FN 14%). Las plaquetas tuvieron mejor rendimiento (AUC 0,77; S 86%; E 56%; FN 14%) que la RH (AUC 0,74; S 43%; E 74%; FN 57%). La RE fue el mejor predictor de VNT (AUC 0,85; S 93%; E 65%; FN 7%) con un punto de corte óptimo de 39 kPa. La combinación de RE y plaquetas mejoró la precisión (AUC 0,86) aunque con un mayor porcentaje de FN (S 79%; E 75%; FN 21%). Conclusiones: La RE mostró una mayor capacidad diagnóstica para predecir VE y VNT en pacientes con CBP, superando a los criterios de Baveno VII y a sus componentes individuales. Además, permitió una identificación más precisa de la HPCS, incluso en pacientes en fases precirróticas.

Reported cases of acute liver injury with autoimmune features post-COVID-19 vaccination raise questions about whether this represents vaccine-triggered autoimmune hepatitis (AIH) or self-limiting drug-induced autoimmune-like hepatitis (DI-ALH). We report follow-up data to determine if the disease course is self-limiting or immunosuppression-dependent.

Rising antimicrobial resistance of Helicobacter pylori is a public health challenge. Genomic-based susceptibility testing allows for the identification of resistance-associated mutations, complementing conventional diagnostics and advancing towards pathogen-based personalised therapies. Our study aimed to identify genes and mutations involved in antimicrobial resistance in H pylori and evaluate the extent to which these markers can be used as predictors of phenotypic resistance against clarithromycin and levofloxacin.

Pratarmė. Mieli studentai, Gastroenterologija yra viena įdomiausių ir greičiausiai besiplėtojančių medicinos sričių. Dėl mokslo ir technologijų pažangos XXI a. gastroenterologija apima vis platesnį kepenų ir virškinamojo kanalo ligų, gydymo metodų spektrą. Tai neabejotinai viena įvairiapusiškiausių specialybių, kur akivaizdi klinikinių įgūdžių, molekulinių ir ultragarsinių tyrimų bei sudėtingų endoskopinių intervencijų sąsaja. Uždegiminės žarnyno ligos, retos virškinamojo kanalo ligos, mikrobiotos ir kepenų transplantacija yra tik nedidelė dalis sričių, kurios yra patikėtos gydytojams gastroenterologams. Šis Lietuvos sveikatos mokslų universiteto Medicinos akademijos Medicinos fakulteto Gastroenterologijos klinikos (toliau - Gastroenterologijos klinika) kolektyvo parengtas vadovėlis yra skirtas studentams, siekiantiems susipažinti su gastroenterologijos pagrindais. Jau beveik 30 metų Gastroenterologijos klinika aktyviai dalyvauja rengiant tarptautines diagnostikos ir gydymo gaires, yra prestižinių tarptautinių mokslo projektų ir konsorciumų dalyvė, o 2020 m. klinika tapo ir asocijuota Europos retų kepenų ligų tinklo nare. Mūsų klinikos mokslinių tyrimų rezultatai yra publikuojami prestižiniuose mokslo leidiniuose: Nature, Lancet, New England Journal of Medicine, Nature Genetics ir kituose. Rengdami šį vadovėlį stengėmės perteikti visą klinikos sukauptą ilgametę pedagoginę ir klinikinę patirtį bei naujausius mokslo pasiekimus. Tikimės, kad šis vadovėlis ne tik suteiks Jums pagrindinių žinių apie gastroenterologiją, bet ir paskatins rinktis šią specialybę rezidentūros studijose. Autorių vardu prof. Juozas Kupčinskas

Introduction: Over recent decades, the study of the bacterial microbiome has gained increasing attention due to its vital role in human health. The development of the gut microbiome is especially critical during infancy, as it supports nutrient absorption, metabolic regulation, and immune system maturation. Several perinatal factors, including delivery mode, gestational age, and health status, have been shown to influence micro -biome establishment. Preterm and low-birth-weight infants, in particular, face heightened vulnerability to disruptions in microbiome development, which may contribute to adverse health outcomes. Aims & Methods: This study aimed to analyze the longitudinal development of the gut microbiome in preterm, low-birth-weight neonates over the first two months of life and to identify microbial patterns and alterations associated with delivery mode, gestational age, and clinical conditions. The study cohort included 115 low-birth-weight preterm infants and 99full-term, normal-weight controls. Stool samples from preterm infants were collected at multiple time points between day 1 and day 61 of life and grouped into six age categories for analysis. In total, 819 stool samples were examined. DNA was extracted and amplified targeting the V3–V4 region of the 16S rRNA gene, followed by sequencing on the Illumina MiSeq platform. Microbiome data were analyzed using bioinformatic and statistical tools to assess taxonomic composition, alpha diversity, and beta diversity. Results: Significant differences in microbiome profiles were associated with gestational age, mode of delivery, postnatal age, maternal medication, and the presence of necrotizing enterocolitis (NEC). Bacterial com-munities began to stabilize between days 26 and 35. A total of 56 bacterial genera — including Bifidobacterium, Clostridium, Escherichia-Shigella, Gemella, Klebsiella, Lactobacillus, and Streptococcus — showed a positive correlation with infants’ age in days, while 31 genera — including Bacillus, Cutibacterium, Flavobacterium, Macrococcus, Pseudomonas, and Staphylococcus — were negatively correlated. Eighteen bacterial genera were associated with the mode of delivery at various time points. Genera such as Fusobacterium, Bacteroides, Entero-coccus, Streptococcus, Gemella, and Corynebacterium were more commonly associated with vaginal birth, while Staphylococcus, Rahnella, Yokenella, Millisia, Negativicoccus, Finegoldia, Haemophilus, Acinetobacter, Conservatibacter, Serratia, Stenotrophomonas, and Peptoniphilus were associated with Caesarean section delivery. Moderate differences in early-life microbiome composition were also ob -served between low-birth-weight preterm and full-term infants. Conclusion: Gut microbiome development in preterm, low-birth-weight newborns is strongly influenced by clinical and perinatal factors, particularly during the first month of life. Mode of delivery, gestational maturity, and disease presence such as NEC contribute to microbial variability and delayed community stabilization. These findings highlight the importance of early-life monitoring and tailored interventions to support healthy microbiome development in vulnerable neonates.

Introduction: Microscopic colitis (MC) refers to two pathologies – Collagenous colitis (CC) and Lymphocytic colitis (LC) that cause chronic watery diarrhoea, urgency, incontinence leading to significantly decreased quality of life 1.It is thought that MC develops due to a pathological immune response to intestinal luminal antigens in genetically predisposed individuals, with microbiota playing an important role2, 3. However, the pathogenesis of MC is still unclear. Aims & Methods: The aim of this study was to identify and characterize changes in bacterial composition of MC patients in terminal ileum and different colonic segments and determine its relation to the clinical course of disease. Biopsies from terminal ileum and six segments of the colon were collected during diagnostic colonoscopies. DNA extraction was performed using All Prep DNA/RNA Micro Kit (Qiagen) following the manufacturer’s instructions. To determine bacterial composition, sequencing of the 16S rRNA variable region V3-V4 was conducted using the 27F and 338R polymerase chain re-action primers and sequenced on a MiSeq (2×250 bp; Illumina, Hayward, CA). Bioinformatic analysis was performed using DADA2, and taxonomic classification was carried out with the RDP classifier. Results: Biopsy samples from 20 active CC patients, 20 active LC patients, and 50 controls demonstrated distinct microbial profiles across different intestinal segments, as revealed by beta-diversity and differential com-positional analyses. Compared with controls, CC patients had consistent alterations in three bacterial families throughout the entire colon, with Erysipelato clostridiaceae and Coriobacteriaceae decreased and Pasteurellaceae increased. Additionally, 35 families had segment-specific changes, and 25 families displayed altered abundance in the terminal ileum.LC patients exhibited a consistent increase in Erisypelotrichaceae across the entire colon, with 38 other families showing segmental changes, and12 families displaying altered abundance in the terminal ileum. Com-paring LC and CC revealed a significantly different bacterial profile. LC showed lower abundance across many families, particularly in the right colon and terminal ileum. After sample collection, 15 CC patients and 12 LC patients received budesonide, with 3 CC and 2 LC patients having incomplete response. Beta diversity analysis revealed significant differences in the ascending colon and left side of the colon of CC patients based on response to budesonide. Patients with incomplete response to budesonide had an increased abundance of the genus Paucibacter. Similar tendencies were not observed in LC.1 CC patient exhibited a quiescent disease course, 6 reached a sustained remission after treatment, 7 had a relapsing and 6 had a chronic active dis-ease. Significant differences in beta diversity were observed in transverse, descending colon and rectum. Beta diversity of the descending colon had a medium correlation with disease behaviour. In the LC group 6 patients had a quiescent disease, 8 had a sustained remission after treatment, 3 exhibited a relapsing and 4 had a chronic active disease. No significant correlation between microbiota and disease behaviour was observed in LC. Conclusion: This study showed significant differences in bacterial com-position between CC, LC and controls in the terminal ileum and colon. In both CC and LC, bacterial alterations were not consistent throughout the entire colon but varied between different colonic segments. Microbiome differences based on response to budesonide and disease behaviour were observed in CC, but not LC.

Background: Cirrhosis is increasing in prevalence but is hard to diagnose in the compensated stage. Gut microbiota are altered in cirrhosis, but studies find greatest differences centered on the easily diagnosable decompensated cirrhosis. Also there are major countrylevel variations. Aim: determine a gut metagenomic signature separating compensated cirrhosis from healthy controls across a global cohort. Methods: Compensated cirrhosis (comp) patients & healthy controls were recruited from seven countries. Clinical data, including demographics, cirrhosis severity (MELD, complications, medications), & dietary were collected. Stool samples underwent deep metagenomic sequencing & analysis using MetaPhlAn & MaAsLin2. Model evaluation was performed using repeated stratified 3-fold cross-validation with SMOTE applied within each training fold to address class imbalance. Models were trained on 70% of the full dataset & internally validated on the remaining 30%. Random forest (RF) model performance was assessed on the held-out test folds only. The final model was also tested separately in each country cohort. Results: We enrolled 618 participants (Comp =299; controls = 319) from 7 countries (USA n = 109, Türkiye n =95, South Korea n = 99, Denmark n= 66, Lithuania n =72, Brazil n =101, & Mexico n= 85) . Comp pts were older (59 ± 9 vs 50 ± 16, p <0.001) & more likely to be men (57 vs 42%, p< 0.001) consistently across countries. Major etiologies were alcohol 25%, HCV 24%, MASH 21% & HBV 16%. Microbiome analysis: Shannon diversity & richness (FigA) were lower in comp in all countries except Türkiye & Denmark (where only richness showed a significant decrease). β-diversity adjusting for demographics showed significant differences in microbial community structure between comp & controls. Microbial differences: In the entire cohort, 381 species were significantly different between controls and comp. 6 species were significantly different in five of seven countries. A set of 182 bacteria, significantly different in ≥2 countries, was selected as input features for RF model development. The final RF model, consisting of 40 species (Erysipelatoclostridium ramosum, Streptococcus anginosus, Veillonella parvula, Rothia mucilaginosa, Eubacterium rectale, Coprococcus catus, Bifidobacterium dentium, & Parabacteroides goldsteinii among others), achieved an AUC of 80.6% with an NPV of 83.2% (Fig B). Country-specific testing of the globally trained model demonstrated consistently strong within-cohort performance across all seven countries (Fig C). Conclusion: Gut metagenomic profiles effectively distinguish compensated cirrhosis from healthy controls across diverse geographic populations with granular metadata. Despite inter-country variability, a shared subset of bacterial features enabled robust and consistent model performance. These findings support the potential of microbiome-based tools for early detection of cirrhosis.

Background: In Lithuania National HCV screening program started in May, 2022. General practitioners (GPs) received special promoting fee for serological HCV antibody testing: 1. For people born between 1945 and 1994 (once in a lifetime) and 2. For people who inject drugs (PWID) or HIV-positive people (annual testing). This initiative is the first in Central and Eastern Europe. The aim of this study was to assess the results of the first 34 months of the programme and evaluate the different scenarios for achieving the WHO 2030 targets. Methods: GPs invited people to perform a serum blood test for HCV antibodies. Anti-HCV+ patients were referred to a gastroenterologist or infectologist for HCV RNA testing, and if result was positive, direct-acting antiviral (DAA) therapy was prescribed. Information about patients was obtained from the National Health Insurance Fund. The Markov disease progression model elaborated by the CDA Foundation was used to assess HCV elimination progress. The data from the 2022-2023 screening were used as inputs. Three scenarios were developed: the ‘Base’ scenario - return to pre-screening program level in 2023 and 2 scenarios with different extents of treatment. Results: At the beginning of 2022, about 1.8 million people born in 1945-1994 lived in Lithuania. Between May 5, 2022 and February 28, 2025, from this population 1362472 people (75.7%) were tested for HCV antibodies. AntiHCV+ were found in 1.28% of cases. In the risk group, 8396 PWID and/or HIV+ people were screened, of whom 28.9 % were seropositive. Among anti-HCV+ persons 83.8% was from population and 16.2 % from risk groups. Specialists consulted 58% anti-HCV+ persons and viremia was detected in 53,1 %. Among anti-HCV+ persons from population specialist consulted 63%, but only 29% from risk group (p < 0.001). During 34-month (May 2022- February 2025) period 3 times more HCV patients were treated with DAA than during the same period before starting of the program (7577 vs 2470). The Markov disease progression model to assess HCV elimination progress showed the following scenarios: Scenario 1: if the same number of patients are treated as before the screening, the WHO targets will not be reached. Scenario 2: treating 70% of infected patients will meet most but not all WHO targets. Scenario 3: by treating all infected patients by 2030, the WHO target will be met by saving 150 lives and preventing 90 new cases of decompensated cirrhosis and 120 cases of hepatocellular carcinoma. Conclusion: In a European country with a moderate HCV seroprevalence, a population-based screening program is feasible and the number of patients treated has increased more than 3-fold in the first 34 months. Current status of the program predict that till 2030 country will meet most but not all WHO targets (the second scenario). Special measures to increase motivation and compliance of risk group patients to program logistic are necessary to achieve all WHO 2030 targets in Lithuania.

Fecal microbiota transplantation is an effective treatment method for recurrent Clostridioides difficile infection. Widely used enteric tube and colonoscopy methods demonstrate excellent efficacy and safety results. Recent data suggest that new fecal microbiota transplantation methods using oral capsules may provide a less invasive approach. In this study, we aimed to compare primary fecal microbiota transplantation efficacy as well as short- and long-term safety of two different administration routes: oral capsules and enteric tube.

Abstract Collagenous colitis (CC) and lymphocytic colitis (LC), subtypes of microscopic colitis (MC), are associated with inconvenient symptoms that significantly reduce patients’ quality of life. This study uses a novel murine model to explore gut microbiota’s role in MC pathogenesis. We hypothesize that specific alterations in the intestinal microbiome play a crucial role in MC development, marked by the suppression of beneficial bacterial populations and the proliferation of potentially harmful species Our research employs C57BL/6 mice (8 weeks old, n ¼ 10/group) across seven treatment groups, utilizing antibiotic treatment, bowel cleansing, and fecal microbiota transplantation(FMT) from MC patients. Through 16S rRNA sequencing and blood analysis at multiple time points, we aim to identify microbial signatures associated with MC and correlate gut microbiota changes with post-FMT MC symptoms. Results reveal significant microbial and host physiological alterations in the MC mouse model. Key findings include suppression of Helicobacter and Tyzzerella, alongside increased Parabacteroides across treatment groups. Immune cell analysis demonstrates a dynamic pattern, with white blood cell and lymphocyte counts initially declining, peaking at 8 weeks, and stabilizing by 24 weeks. Granulocytes exhibit significant fluctuations, peaking at 16 weeks, while monocyte levels remain stable. This study establishes a temporal model for MC, highlighting distinct changes in microbiome and immune cell dynamics. Our findings provide crucial insights into the interplay between FMT and host-microbe interactions in MC pathogenesis, potentially informing novel diagnostic and therapeutic strategies for the disease.