Hasil untuk "Diseases of the digestive system. Gastroenterology"

Shirin Yousefi, Mahsa Sadeghi-Adl, Samira Tarashi et al.

Abstract Background Opioid dependence, particularly morphine, has been linked to gut microbiota dysbiosis and systemic inflammation, yet the interplay between gut microbial alterations and hepatic inflammatory responses remains poorly understood. Methods Fifty male Wistar rats were separated into two groups, one received escalating morphine doses (5 to 30 mg/kg over 10 days), while the other acted as a saline control. Fecal samples were collected at baseline, on days 5 and 10 of treatment, and after a 10-day withdrawal. DNA was extracted for qPCR analysis of Lactobacillus, Bifidobacterium, Clostridium, Bacteroides, and Faecalibacterium. Liver tissues were examined for inflammatory markers (TNF-α, IFN-γ, IL-6, NF-κB) using RT-qPCR after treatment and withdrawal. Results A significant decline in Lactobacillus (P = 0.011) and Bifidobacterium (P = 0.003) following morphine treatment, with partial recovery observed after withdrawal (P = 0.014; P = 0.0009), yet levels remained below baseline. Conversely, Clostridium levels increased significantly during treatment (P = 0.0001), persisting at elevated levels post-withdrawal (P = 0.0001). Bacteroides and Faecalibacterium also exhibited decreased abundances during morphine treatment (P > 0.05; P = 0.00009), with limited recovery thereafter (P > 0.05; P = 0.00008). Hepatic analysis revealed elevated levels of TNF-α (P < 0.0001), IL-6 (P = 0.005), and NF-κB (P = 0.41), alongside a significant reduction in IFN-γ (P < 0.001) expression in the morphine group compared to controls. After withdrawal, TNF-α (P < 0.01) and IFN-γ (P = 0.004) levels decreased, while NF-κB (P = 0.03) and IL-6 (P = 0.4(remained elevated, indicating persistent inflammatory responses. Conclusion Morphine causes lasting gut dysbiosis and liver inflammation, indicating disruption of the gut-liver axis in opioid dependence. These results emphasize morphine’s impact on gut microbiota and liver health, suggesting significant long-term effects of opioid use. Targeting microbiota modulation and anti-inflammatory approaches may offer therapeutic options for opioid-related conditions.

Bjørn Moum, Marte Lie Høivik, Benoit Follin-Arbelet et al.

The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) study group was initially established to ascertain the precise incidence of inflammatory bowel disease (IBD) within a specific region of Norway, thereby contributing to a global initiative aimed at elucidating the increasing prevalence of these conditions. The study was designed to foster close collaboration among national and international experts, including gastroenterologists, specialists, and private practitioners within the study area. Patients were enrolled prospectively over a 4-year period, from January 1, 1990, to December 31, 1993, based on established international diagnostic criteria and a follow-up protocol encompassing 1, 5, 10, 20, and 30-year intervals. The consortium operated through a bidirectional communication network connecting primary and secondary specialized hospitals, encompassing general hospitals and research laboratories. In 2017, the IBSEN III study was launched to facilitate a comparison of clinical and epidemiological outcomes with those of the original IBSEN study, involving an expanded catchment area and more extensive clinical and molecular assessments of the cohort. This narrative review reflects the consortium’s activities through 2024 and provides comprehensive details regarding the research areas and outcomes of national and international collaborations for both IBSEN study.

Kristian Paul Mallon, Kristian Paul Mallon, Ciara McBride et al.

IntroductionThere is accumulating evidence that certain perinatal and prenatal factors may contribute to the onset of IBD, however evidence on some risk factors is inconsistent. The present study seeks to extend current knowledge on these risk factors and provide a comprehensive overview of which factors are associated with IBD onset and their direction of effect.MethodsA Systematic review and meta-analysis of case-control, cohort studies and randomised controlled trials (RCTs) investigating the association between parental and perinatal factors and onset of IBD was conducted. Studies were included if they reported details on patients with a diagnosis of IBD (including Crohn’s Disease [CD] and/or Ulcerative Colitis [UC]), defined and measured according to endoscopic, radiological, and histopathological findings, confirmed by a gastroenterologist or physician. Computerised bibliographic searches of Ovid MEDLINE, Web of Science, and the Cochrane Library were conducted from 01/01/2002 to the 01/01/2022. Where possible, summaries of the effects of perinatal and prenatal variables for each study were provided by calculating risk estimates using the DerSimonian and Laird random effects model. Levels of heterogeneity were evaluated using the I² statistic. Data were analysed using Stata version 17. Study protocol details are published on the International prospective register of systematic reviews (PROSPERO), registration number: CRD42022290798.ResultsFifteen eligible studies were identified, encompassing 9 case-control and 6 cohort studies, with no RCTs identified. A total of 6,507 patients with IBD were described in these studies (1,819 UC; 3,908 CD; 754 IBD; 4 IBD-unclassified patients). Three predictors of IBD risk were identified. Any poor maternal health or disease in mother during pregnancy (Pooled RR 1.78, 95% CI 1.24-2.31), maternal IBD (Pooled RR 4.59, 95% CI 1.68-7.50), and familial history (Pooled RR 2.87, 95% CI 1.80-3.93), were associated with an increased risk of overall IBD.DiscussionThis systematic review and meta-analysis suggests parental and perinatal factors may have a role in the onset of IBD. These findings highlight the importance of early-life exposures for later IBD development and indicate a requirement for further research in this area.Systematic Review RegistrationPROSPERO, identifier (CRD42022290798).

Gianenrico Rizzatti, Bertrand Napoléon, Fabrice Caillol et al.

Madelyn Agaciak, Molla M Wassie, Kalindra Simpson et al.

Abstract Background and Aim Surveillance colonoscopy for colorectal cancer (CRC) is generally not recommended beyond 75 years of age. The study determined incidence and predictors of advanced adenoma and CRC in older individuals undergoing surveillance colonoscopy. Methods This was a retrospective cohort study of asymptomatic older participants (≥75 years), enrolled in a South Australian CRC surveillance program who underwent colonoscopy (2015–2020). Clinical records were extracted for demographics, personal or family history of CRC, comorbidities, polypharmacy, and colonoscopy findings. The associations between clinical variables and advanced adenoma or CRC at surveillance were assessed with multivariable Poisson regression analysis. Results Totally 698 surveillance colonoscopies were analyzed from 574 participants aged 75–91 years (55.6% male). The incidence of CRC was 1.6% (11/698), while 37.9% (260/698) of procedures had advanced adenoma detected. Previous CRC (incidence rate ratio [IRR] 5.9, 95% CI 1.5–22.5), age ≥85 years (IRR 5.8, 95% CI 1.6–20.1) and active smoking (IRR 4.9, 95% CI 1.0–24.4) were independently associated with CRC diagnosis, while advanced adenoma at immediately preceding colonoscopy (IRR 1.6, 95% CI 1.3–2.0) and polypharmacy (IRR 1.2, 95% CI 1.0–1.5) were associated with advanced adenoma at surveillance colonoscopy in asymptomatic older participants (≥75 years). Conclusion Advanced neoplasia was found in more than one third of the surveillance procedures completed in this cohort. Continuation of surveillance beyond age 75 yeasrs may be considered in participants who have previous CRC or are active smokers (provided they are fit to undergo colonoscopy). In other cases, such as past advanced adenoma only, the need for ongoing surveillance should be considered alongside participant preference and health status.

Yaojie Liang, Xufeng Luo, Stefan Schefczyk et al.

Background &amp; Aims: Hepatitis B surface antigen (HBsAg) drives hepatocarcinogenesis. Factors and mechanisms involved in this progression remain poorly defined, hindering the development of effective therapeutic strategies. Therefore, the mechanisms involved in the HBsAg-induced transformation of normal liver into hepatocellular carcinoma (HCC) were investigated. Methods: Hemizygous Tg(Alb1HBV)44Bri/J mice were examined for HBsAg-induced carcinogenic events. Gene set-enrichment analysis identified significant signatures in HBsAg-transgenic mice that correlated with endoplasmic reticulum (ER) stress, unfolded protein response, autophagy and proliferation. These events were investigated by western blotting, immunohistochemical and immunocytochemical staining in 2-, 8- and 12-month-old HBsAg-transgenic mice. The results were verified in HBsAg-overexpressing Hepa1-6 cells and validated in human HBV-related HCC samples. Results: Increased BiP expression in HBsAg-transgenic mice indicated induction of the unfolded protein response. In addition, early-phase autophagy was enhanced (increased BECN1 and LC3B) and late-phase autophagy blocked (increased p62) in HBsAg-transgenic mice. Finally, HBsAg altered lysosomal acidification via ATF4- and ATF6-mediated downregulation of lysosome-associated membrane protein 2 (LAMP2) expression. In patients, HBV-related HCC and adjacent tissues showed increased BiP, p62 and downregulated LAMP2 compared to uninfected controls. In vitro, the use of ER stress inhibitors reversed the HBsAg-related suppression of LAMP2. Furthermore, HBsAg promoted hepatocellular proliferation as indicated by Ki67, cleaved caspase-3 and AFP staining in paraffin-embedded liver sections from HBsAg-transgenic mice. These results were further verified by colony formation assays in HBsAg-expressing Hepa1-6 cells. Interestingly, inhibition of ER stress in HBsAg-overexpressing Hepa1-6 cells suppressed HBsAg-mediated cell proliferation. Conclusions: These data showed that HBsAg directly induces ER stress, impairs autophagy and promotes proliferation, thereby driving hepatocarcinogenesis. In addition, this study expanded the understanding of HBsAg-mediated intracellular events in carcinogenesis. Impact and implications: Factors and mechanisms involved in hepatocarcinogenesis driven by hepatitis B surface antigen (HBsAg) are poorly defined, hindering the development of effective therapeutic strategies. This study showed that HBsAg-induced endoplasmic reticulum stress suppressed LAMP2, thereby mediating autophagic injury. The present data suggest that restoring LAMP2 function in chronic HBV infection may have both antiviral and anti-cancer effects. This study has provided insights into the role of HBsAg-mediated intracellular events in carcinogenesis and thereby has relevance for future drug development.

Mercè Soler-Font, I. Aznar-Lou, L. Basile et al.

This study aimed to estimate the cost and factors associated with severe hospitalized patients due to influenza in unvaccinated and vaccinated cases. The study had a cross-sectional design and included three influenza seasons in 16 sentinel hospitals in Catalonia, Spain. Data were collected from a surveillance system of influenza and other acute respiratory infections. Generalized linear models (GLM) were used to analyze mean costs stratified by comorbidities and pregnancy. Multivariate logistic models were used to analyze bacterial coinfection, multi-organ failure, acute respiratory distress syndrome, death and ICU admission by season and by vaccination status. Costs of ICU, hospitalization and total mean costs were analyzed using GLM, by season and by vaccination status. All models were adjusted for age and sex. A total of 2742 hospitalized cases were included in the analyses. Cases were mostly aged ≥ 60 years (70.17%), with recommended vaccination (86.14%) and unvaccinated (68.05%). The ICU admission level was statistically significant higher in unvaccinated compared to vaccinated cases. Costs of cases with more than or equal to two comorbidities (Diff = EUR − 1881.32), diabetes (Diff = EUR − 1953.21), chronic kidney disease (Diff = EUR − 2260.88), chronic cardiovascular disease (Diff = EUR − 1964.86), chronic liver disease (Diff = EUR − 3595.60), hospitalization (EUR 9419.42 vs. EUR 9055.45), and total mean costs (EUR 11,540.04 vs. 10,221.34) were statistically significant higher in unvaccinated compared to vaccinated patients. The influenza vaccine reduces the costs of hospitalization. There is a need to focus strategies in recommended vaccination groups.

I.V. Koshurba, F.V. Hladkykh, M.O. Chyzh

Background. Peptic ulcer disease has a leading place in the overall structure of digestive diseases: its prevalence is 6.00–10.0 % of the population in developed countries, and mortality ranges from 6 to 9.7 per 100 thousand population. An important etiological factor of this pathology is the neuropsychological background, prima­rily stress, which under repeated exposure becomes the initiating factor of physiological imbalance between the elements of aggression and protection of the gastric mucosa. The purpose was to establish the mechanisms of the protective activity of placental cryoextract based on the biochemical indicators of lipid peroxidation and antioxidant protection in the gastric mucosa on a model of stress-induced erosive-ulcerative damage. Materials and methods. Stu­dies were performed on 28 nonlinear laboratory male rats weig­hing 200–220 g. Stress-induced gastric ulcer was modeled under water-immobilization stress in rats according to the K.Y. Takagi et al. In the gastric mucosa, the content of reactants with thiobarbituric acid was determined spectrophotometrically by the method of T. Asakawa et al., catalase acti­vity — spectrophotometrically by the method of M.A. Korolyuk et al., the content of reduced glutathione — spectrophotometrically by the method of E.D. Beutler et al., the level of adenyl nucleotides was determined using chromatographic me­thod. Energy charge was calculated by D.E. Atkinson equation. ­Results. The prophylactic five-day use of placental cryoextract led to a decrease in the severity of stress-induced lipid peroxidation and ener­gy imbalance in the gastric mucosa. Thus, it was found that rats who received placental cryoextract had a statistically significant (p < 0.001) increase in adenosine triphosphate content by 73.3 %, an increase in adenosine diphosphate (p < 0.001) by 37.3 % and a decrease in adenosine monophosphate (p < 0.001) by 47.6 % that led to an increase in energy charge (p < 0.001) by 35.1 % compared to rats exposed to water-immobilization stress without correction (control group). It was shown that the use of placental cryoextract led to a statistically significant (p < 0.001) increase in the antioxidant-prooxidant index by 3.1 times versus control group, which was (26.60 ± 0.96) and (8.60 ± 0.43), respectively. Conclusions. Prophylactic five-day administration of placental cryoextract leads to the restoration of balance in the system of adenyl nucleotides and, accor­dingly, to a statistically significant (p < 0.001) increase in the ener­gy charge by 35.1 % compared to the control animals. Inhibition of stress-induced hyperactivation of lipid peroxidation in the gastric mucosa is one of the mechanisms of its antiulcer activity.

M. Fujii, M. Kobayakawa, Kiyoshi Saito et al.

Simple Summary Neurofibromatosis type 2 (NF2) is a rare genetic hereditary disease characterized by multiple central nervous system tumors, most frequently bilateral vestibular schwannomas (VSs). No chemotherapeutic agents are available for clinical use, and surgery and radiotherapy are the only therapeutic options available now. Still, neither treatment option alleviates hearing loss in patients with NF2 and VS; they may even exacerbate it. However, bevacizumab has been reported to be effective in suppressing the tumor’s growth and has shown unprecedented efficacy in improving hearing. We describe a new ongoing and novel clinical trial, BeatNF2, a randomized, double-blinded, placebo-controlled, multicenter trial to assess bevacizumab’s efficacy and safety in patients with NF2. The study’s primary endpoint is improved hearing function 24 weeks after the beginning of the treatment protocol. Abstract Neurofibromatosis type 2 (NF2) causes bilateral vestibular schwannomas (VSs), leading to deafness. VS is treated by surgery or radiation, but neither treatments prevent hearing loss. Bevacizumab was found to be effective in suppressing the tumor’s growth and may help to improve hearing. We are conducting a randomized, double-blind, multicenter clinical trial to verify the efficacy and safety of bevacizumab in NF2-related VS. The primary objective is to evaluate the efficacy of bevacizumab in improving hearing in the affected ear. One of the secondary objectives is to evaluate bevacizumab’s efficacy in rechallenge treatment in relapsed cases. Sixty patients will randomly receive either bevacizumab or a placebo and will be clinically observed for 48 weeks in the initial intervention phase. In the first half (24 weeks), they will receive either 5 mg/kg of bevacizumab or a placebo drug. In the second half, all patients will receive 5 mg/kg of bevacizumab. If hearing function deteriorated in a patient who had shown improvement during the first phase, a rechallenge dose with bevacizumab would be offered.

Shin Ju Oh, Ga Young Shin, Hosim Soh et al.

Background/Aims Infliximab (IFX) has proven effective as rescue therapy in steroid-refractory acute severe ulcerative colitis (ASUC), however, the long-term real-world data are scarce. Our study aimed to assess the long-term treatment outcomes of IFX in a real-life cohort. Methods We established a multicenter retrospective cohort of hospitalized patients with ASUC, who met Truelove and Witt’s criteria and received intravenous corticosteroid (IVCS) or IFX during index hospitalization between 2006 and 2016 in 5 university hospitals in Korea. The cohort was systematically followed up until colectomy, death or last follow-up visit. Results A total of 296 patients were followed up for a mean of 68.9 ± 44.0 months. During index hospitalization, 49 patients were treated with IFX; as rescue therapy for IVCS failure in 37 and as first-line medical therapy for ASUC in 12. All patients treated with IFX avoided colectomy during index hospitalization. The cumulative rates of rehospitalization and colectomy were 20.4% and 6.1% at 3 months and 39.6% and 18.8% at the end of follow-up, respectively. Patients treated with IFX presented with significantly shorter colectomy-free survival than IVCS responders (P=0.04, log-rank test). Both cytomegalovirus colitis and Clostridioides difficile infection (CDI) were the significant predictors of colectomy in the overall study cohort (hazard ratios of 6.57 and 4.61, respectively). There were no fatalities. Conclusions Our real-world cohort study demonstrated that IFX is an effective therapeutic option in Korean patients with ASUC, irrespective of IFX indication. Aggressive vigilance for cytomegalovirus colitis and CDI is warranted for hospitalized patients with ASUC.

D. Loconsole, M. Giordano, F. Centrone et al.

Shiga toxin-producing Escherichia coli (STEC) infections result in a significant public health impact because of the severity of the disease that, in young children especially, can lead to hemolytic–uremic syndrome (HUS). A rise in the number of HUS cases was observed in the Apulia region of Italy from 2013 to 2017, and so, in 2018, a symptom-based surveillance system for children with bloody diarrhea (BD) was initiated in order to detect and manage STEC infections. The objective of the study was to describe the epidemiology of STEC infections in children from June 2018 to August 2019. Children <15 years old with BD were hospitalized and tested for STEC. Real-time PCR for virulence genes (stx1, stx2, eae) and serogroup identification tests were performed on stool samples/rectal swabs of cases. STEC infection was detected in 87 (10.6%) BD cases. The median age of STEC cases was 2.7 years, and 60 (68.9%) were <4. Of these 87 cases, 12 (13.8%) came from households with diarrhea. The reporting rate was 14.2/100,000, with the highest incidence in cases from the province of Bari (24.2/100,000). Serogroups O26 and O111 were both detected in 22/87 (25.3%) cases. Co-infections occurred in 12.6% of cases (11/87). Twenty-nine STEC were positive for stx1, stx2, and eae. Five cases (5.7%) caused by O26 (n = 2), O111 (n = 2), and O45 (n = 1) developed into HUS. A risk-oriented approach based on the testing of children with BD during the summer may represent a potentially beneficial option to improve the sensitivity of STEC surveillance, not only in Italy but also in the context of Europe as a whole.

A. Sulaiman, Juferdy Kurniawan, C. Jasirwan et al.

By late December 2019, a novel beta-coronavirus, named as COVID-19 (2019-nCoV), was discovered in Wuhan, Hubei Province, China which epidemiologically linked to a Huanan seafood market in Wuhan. Coronavirus Disease 2019 or COVID-19 cases are growing rapidly from Wuhan to many countries, finding the health care system unprepared to face this threat. No effective drugs are clinically approved to manage the disease and strategies to protect the most vulnerable from developing severe illness and infection is still unclear. Information on how COVID-19 virus infection may affects many organs, especially the liver and the relevance of pre-existing liver disease in patients as a risk factor for the infection or disease severity are still scarce and inconclusive. Besides, the recommendation and consideration in liver transplant patients, hepatocellular carcinoma, or patient on immunosuppressive therapy still need further analysis Therefore, the information on the mechanism and treatment of COVID-19 related liver injury in patients with or without pre-existing liver disease should be considered.

Patricia Paredes Lascano, Paul Josué Ruiz Chávez, Lorena Monserrat Izurieta Mera et al.

Introduction: Probiotics were described in the 18th century AD, they are living non-pathogenic microorganisms, have been studied since ancient times thanks to their healing and preventive properties. Over time, it has been possible to determine more accurately the mechanism of action by which they cause a beneficial effect on organisms, especially in respiratory, digestive, urinary and allergic diseases. The present work focuses on the usefulness of probiotics as an adjuvant therapy in pediatric pathologies. Objectives: Critically evaluate the recent scientific literature on the clinical uses of probiotics in pediatrics. Material and methods: A systematic review of the scientific literature published in the period 2015-2020 was carried out. A search was conducted on the sites below using the following terms: ''probiotics,'' ''therapeutic uses of probiotics,'' ''clinical uses of probiotics,'' ''uses of probiotics,'' ''Lactobacillus,'' ''Bifidobacterium,'' ''Saccharomyces,'' '' '' probiotics in children,'' history of prebiotics", "probiotics in diarrhea", "probiotics in urinary tract infection", "probiotics in respiratory infections", "Pediatric uses of probiotics", in databases: Medline, Cochrane Database of Systemic Review, New England Journal of Medicine, American Journal of Gastroenterology, Journal of Pediatric Gastroenterology Nutrition, BMJ, Oxford academic, Elsevier, US National Library of Medicine National Institutes of Health. Results:The theoretical references analyzed allowed to determine the most relevant aspects of clinical applications of probiotics in pediatrics: viral acute gastroenteritis, persistent diarrhea, antibiotic-associated diarrhea, prevention of diarrhea by Clostridium difficile, adjuvant treatment for eradication of Helicobacter pylori, Inflammatory bowel disease: reservoritis and Necrotizing Enterocolitis. Conclusions: Probiotic administration has been increased as an adjuvant treatment in multiple pathologies and the few or no adverse effects have been demonstrated in paediatric patients, it is estimated that the risk of developing bacteremia by ingested lactobacilli is less than one million consumers, which reinforces their high safety of use in paediatric patients. Research on probiotics and their relationships with the microbiota continue to provide new knowledge about their mechanisms and their impact on health, which has allowed to delve into their main potential, based on antagonism antimicrobial, microbiota balance restoration and improvement to immune response. There is serious recommendation about its benefit in acute infectious diarrhoea, antibiotic-associated diarrhea, necrotizing enterocolitis in the low-weight, prematurity newborn, its influence on the immune system and other intestinal diseases, improve resistance to infections and allergy states, especially in infants and young children. However, in urinary tract infection and respiratory infections there is no conclusive evidence to recommend the use of probiotics. It is suggested to incorporate probiotics into the national drug table, because as shortened in the duration of acute diarrhoeal disease is demonstrated, this would reduce the hospital stay of paediatric patients, with the consequent reduction in health sector spending

Atike Atalay

G. Labate, P. Modi, A. Timoney et al.

Sang Hyoung Park

A. Komori, A. Tanaka, H. Takikawa et al.

T. Matsumoto

G Thiruvikrama Prakash, Ashok Kumar Das, Syed Habeebullah et al.

Introduction: Gestational diabetes mellitus (GDM) is common and is accompanied with other comorbidities. Challenges to treatment exist at our institute as it serves women with low income. This study assessed the burden of comorbidities and the outcome of GDM. Methods: This was a prospective, observational study of women with gestational diabetes attending the obstetrics department from September 2012 to April 2014. GDM was diagnosed based on the International Association of Diabetes and Pregnancy Study Groups criteria. Medical comorbidities were noted, and lipid profile was done. All the women were followed up till delivery, and the complications were recorded. Age- and parity-matched pregnant women with normal oral glucose tolerance test were recruited as controls. Results: One hundred and thirty-nine women were followed up till delivery. The average age was 28 years. Eighteen percent had bad obstetric history. The average body mass index was 28.8. Twenty-five percent had gestational hypertension (HTN), and 6.4% had chronic HTN. Thirty percent had hypothyroidism. 65% women received insulin. The glucose values were within the recommended range in 60% of the women. Maternal hypoglycemia occurred in 7 (5%) women. Forty-four percent of the women required cesarean section and 34% had complications either during pregnancy or labor. Three neonates had macrosomia. Twenty-six neonates (20%) required admission to the Neonatal Intensive Care Unit. Four neonates (3%) died. Newborns of mothers whose GDM optimally treated had less complications. Conclusion: Gestational diabetes is associated with HTN, hypothyroidism, obesity, and lipid abnormalities. The majority of women required insulin for treatment and optimal control of blood glucose resulted in lower neonatal complications.

Roggeri DP, Roggeri A

Daniela Paola Roggeri,&nbsp;Alessandro Roggeri ProCure Solutions, Nembro, Bergamo, Italy Purpose: Hepatic encephalopathy (HE) is associated with a reduced survival, an increased risk of hospitalization for recurrences, and a reduced health-related quality of life. The purpose of the present economic analysis was to evaluate the impact on the Italian National Health Service (INHS) expenditure of the treatment with rifaximin 550 mg twice daily (Tixteller&reg;/Tixtar&reg;) for the reduction of the recurrences of overt HE, with respect to the current treatment approach. Patients and methods: Costs associated with patients treated with rifaximin 550 mg twice daily were estimated considering the reduction in hospitalizations for HE recurrences revealed by registrative clinical trial (&minus;50%) applied to the hospitalization rate (42.5%) emerging from an Italian observational real-world study; costs associated with patients not treated with rifaximin were estimated based on the hospitalization rate, resulting from the same Italian observational study. Sensitivity analyses considering possible different discount levels to INHS structures for rifaximin were performed. The INHS perspective for a period of 3 years was considered. Results: The treatment with rifaximin 550 mg twice daily, although increasing drug costs, is associated with a reduction in hospitalizations for HE recurrences that leads to an overall reduction of total costs charged to INHS, which could be estimated, based on the forecasted uptake of the treatment, at about &euro;130,000 in the first year, reaching ~&euro;260,000 in the third year. Considering a possible discount for rifaximin 550 mg to INHS structure of 20%, the total saving at the third year accounts for ~&euro;3,000,000. Moreover, a relevant reduction in the number of hospitalizations and bed days is associated with rifaximin treatment. Conclusion: The treatment with rifaximin 550 mg twice daily, even if associated with an increase in drug expenditure, results in a reduction in total health care costs charged to INHS due to a reduction in hospitalizations for HE recurrences. Keywords: overt hepatic encephalopathy recurrences, health care expenditure, costs, hospitalizations, budget impact