Biliary Dysfunction Research Articles

Cholestatic insult triggers alcohol-associated hepatitis in mice.

Alcohol-associated hepatitis (AH) is a severe, potentially life-threatening form of alcohol-associated liver disease with limited therapeutic options. Existing evidence shows that biliary dysfunction and cholestasis are common in patients with AH and are associated with poorer prognosis. However, the role of cholestasis in the development of AH is largely unknown. We aimed to examine the hypothesis that cholestasis can be an important etiology factor for AH. To study the interaction of cholestasis and alcohol, chronically ethanol (EtOH)-fed mice were challenged with a subtoxic dose of α-naphthylisothiocyanate (ANIT), a well-studied intrahepatic cholestasis inducer. Liver injury was measured by biochemical and histological methods. RNAseq was performed to determine hepatic transcriptomic changes. The impact of inflammation was assessed using an anti-LY6G antibody to deplete the neutrophils and DNase I to degrade neutrophil extracellular traps. ANIT synergistically enhanced liver injury following a 4-week EtOH feeding with typical features of AH, including increased serum levels of ALT, AST, and total bile acids, cholestasis, necrosis, neutrophil infiltration, and accumulation of neutrophil extracellular traps. RNAseq revealed multiple genes uniquely altered in the livers of EtOH/ANIT-treated mice. Analysis of differentially expressed genes suggested an enrichment of genes related to inflammatory response. Anti-LY6G antibody or DNase I treatment significantly inhibited liver damage in EtOH/ANIT-treated mice. Our results support the hypothesis that cholestasis can be a critical contributor to the pathogenesis of AH. A combined treatment of EtOH and ANIT in mice presents biochemical, histological, and molecular features similar to those found in patients with AH, suggesting that this treatment scheme can be a useful model for studying Alcohol-associated Cholestasis and Hepatitis (AlChoHep).

Functional Disorders of the Biliary Tract and Cholelithiasis: Analysis of a Possible Relationship

Aim: Diagnostic criteria for functional disorders of the biliary tract are presented in the materials of the Rome IV consensus, as well as expert councils of Russian and foreign specialists. Episodes of functional biliary pain are caused by a violation of bile outflow through the cystic duct and sphincter of Oddi. It has been suggested that there is a “biliary continuum” in which in some patients’ biliary dysfunction is transformed into cholelithiasis. Key points. Lithogenic bile is considered as the pathophysiological basis for the development of biliary dyskinesia and cholelithiasis. Lithogenic bile provokes inflammation of low grades in the mucous membrane of the biliary tract, decreased contractility of the gallbladder and impaired relaxation of the biliary sphincters, impaired physiological response to cholecystokinin. Changes in motility of the biliary tract may be associated with the influence of hydrophobic bile salts and impaired eicosanoid metabolism. Hyperplasia of the epithelium and muscle layer, hypersecretion of mucin and cholesterol precipitation further impair the outflow of bile. Experimental data and some clinical observations indicate the possibility of transformation of biliary dysfunction into cholelithiasis. Dysfunction of the sphincter of Oddi is one of the possible consequences of cholecystectomy and, in fact, acts as a variant of postcholecystectomy syndrome. The basis for the treatment of biliary dysfunctions are antispasmodics of different classes, which can be combined with ursodeoxycholic acid. The biliary tract-selective antispasmodic hymecromone has shown high effectiveness in relieving biliary pain, which also has a moderate choleretic effect and the ability to prevent the crystallization of cholesterol in bile and can be used both for functional diseases and for cholelithiasis. The domestic drug hymecromone “Odecromone” entered the pharmaceutical market. Conclusion. There is no doubt that the relevance of further study of the patterns of development of biliary dysfunctions and GI is obvious. The study of this problem will contribute to the development of effective preventive approaches, including in the field of nutraceuticals.

The Management of Dysfunctional Gallbladder Disease and the Role of Laparoscopic Cholecystectomy on Symptom Improvement: A Retrospective Cohort Study.

Background Biliary dyskinesia (BD) is a disorder characterised by abdominal pain of biliary origin (i.e., sudden steady pain at the right upper quadrant of the abdomen or the epigastrium, the absence of gallstones on ultrasound (US)), and a decreased gallbladder ejection fraction (GBEF) on a cholecystokinin-cholescintigraphy hepatobiliary iminodiacetic acid (CCK-HIDA) scan. Patients experiencing symptoms suggestive of biliary obstruction, but lacking gallstones, yet exhibiting abnormal gallbladder emptying, may find therapeutic benefit from laparoscopic cholecystectomy. Common symptoms include recurrent, intense, and enduring pain, often exacerbated by fatty food consumption, localised in the upper right quadrant or epigastric region. This pain may radiate to the back or shoulder, persisting for at least 30 minutes but not exceeding several hours, and it is sometimes accompanied by nausea and vomiting. Abnormal gallbladder emptying is typically indicated by a GBEF below 35% on cholescintigraphy following cholecystokinin administration. Objective This study represents a single-centric review focusing on 88 patients over a five-year period who presented with features of dysfunctional gallbladder and underwent cholescintigraphy. The primary aim was to identify whether there is any role for laparoscopic cholecystectomy in symptom improvement among these patients. Methods This was a retrospective cohort study involving data collection using electronic medical records. Eighty-eight patients who underwent the HIDA scan between January 2019 and December 2023 at Wirral University Teaching Hospital NHS Foundation Trust (WUTH) were identified and separated into two groups, either hypofunctioning gallbladder (EF<35% ) or hyperfunctioning gallbladder (EF>80%). Normal HIDA scan patients (EF between 35%-80%) were excluded. The frequency of laparoscopic cholecystectomy and subsequent symptom improvement were recorded. Results Fifty-one patients were diagnosed with gallbladder dyskinesia (BD). Of these, 36 patients (30 females, mean age 43) were diagnosed with hypofunctional gallbladder (EF<35%), where 17 patients underwent laparoscopic cholecystectomy, resulting in symptom improvement in 10 patients (58.8%). Conversely, 15 patients were diagnosed with hyperfunctional gallbladder (13 females, mean age 48.6). Only two patients (13%) underwent laparoscopic cholecystectomy with 100% symptom improvement in both patients. Conclusions In conclusion, our retrospective study highlights the significance of the HIDA scan in identifying gallbladder hypofunction among patients presenting with biliary symptoms. The findings establish the efficacy of laparoscopic cholecystectomy as a management approach, with a notable proportion of patients experiencing symptom improvement (58.8%). These results contribute to our understanding of biliary dysfunction management and emphasise the importance of individualised treatment strategies for optimal patient outcomes. Further, randomised controlled trials (RCTs) are warranted to validate these findings and explore additional factors influencing symptom resolution in this patient population.

GVHD targets organoid-forming bile duct stem cells in a TGF-β–dependent manner

AbstractGraft-versus-host disease (GVHD) is a major life-threatening complication that occurs after allogeneic hematopoietic cell transplantation (HCT). Although adult tissue stem cells have been identified as targets of GVHD in the skin and gut, their role in hepatic GVHD is yet to be clarified. In the current study, we explored the fate of bile duct stem cells (BDSCs), capable of generating liver organoids in vitro, during hepatic GVHD after allogeneic HCT. We observed a significant expansion of biliary epithelial cells (BECs) on injury early after allogeneic HCT. Organoid-forming efficiency from the bile duct was also significantly increased early after allogeneic HCT. Subsequently, the organoid-forming efficiency from bile ducts was markedly decreased in association with the reduction of BECs and the elevation of plasma concentrations of bilirubin, suggesting that GVHD targets BDSCs and impairs the resilience of BECs. The growth of liver organoids in the presence of liver-infiltrating mononuclear cells from allogeneic recipients, but not from syngeneic recipients, was significantly reduced in a transforming growth factor-β (TGF-β)–dependent manner. Administration of SB-431542, an inhibitor of TGF-β signaling, from day 14 to day 28, protected organoid-forming BDSCs against GVHD and mitigated biliary dysfunction after allogeneic HCT, suggesting that BDSCs are a promising therapeutic target for hepatic GVHD.

Late liver allograft dysfunction: definition, risk factors and outcomes

Introduction. Impaired liver transplant function in the long term often leads to graft loss and the recipient death. There are many causes for the development of a late liver allograft dysfunction and different types of its clinical presentation, but there is no generally accepted definition. This hinders its timely diagnosis, analysis of its prevalence, and also makes it difficult to compare the performance of transplantation programs.Objective. To determine the clinical and prognostic value of late liver allograft dysfunction.Material and methods. The study included 103 cases of cadaveric liver transplantation from donors diagnosed with brain death to 100 recipients, of whom 36% were men, aged 48 years old (40;56) (18–68) at the time of transplant, having MELD score 17 (14;21) (7–41). The follow-up period was 52 months (20;77) (8–180). The cases where the graft loss occurred earlier than 3 months were excluded.The late liver allograft dysfunction was defined as a dysfunction of the transplanted liver, which was manifested by at least one of three following signs and occurred at more than 3 months after transplantation: 1) increased aspartate aminotransferase, alanine aminotransferase and/or gamma glutamyl transferase, alkaline phosphatase, bilirubin; 2) impaired synthetic function (increased international normalized ratio, decreased antithrombin III, cholinesterase); 3) liver cirrhosis complications (signs of portal hypertension, ascites, encephalopathy). The following limits were chosen as a diagnostic threshold for laboratory parameter abnormalities: more than 2 upper limits of normal for total bilirubin, more than 1.5 upper limits of normal for the levels of alanine or aspartic aminotransferases, more than 1.5 upper limits of normal for gamma-glutamyltransferase or alkaline phosphatase, more than 1.6 of normal for international normalized ratio.Results. Late liver allograft dysfunction was diagnosed at least once in 64% of recipients. Through the postoperative course, the proportion of patients with late dysfunction varied from 22% to 40%. The etiology of late liver allograft dysfunction was viral (38%), unknown (25%), biliary (19%), immune (17%), and vascular (1%). Late liver allograft dysfunction was reversible in 75% of cases, persistent in 17%, progressive in 8% of cases. Progressive late liver allograft dysfunction led to a graft loss in all cases observed.Recipients with late liver allograft dysfunction were found to have had a 33% higher incidence of early allograft dysfunction (OR 4.7, 95% CI [1.8–12.3]); the incidence of biliary dysfunction was 3.1 times higher with distant choledochojejunostomy (OR 3.9, 95% CI [1.1–13.9]); in patients with autoimmune and cholestatic disease, the incidence of immune dysfunction was 4.8 times higher (OR 5.8, 95% CI [1.7–20.3]).Conclusion. The progressive nature of late liver allograft dysfunction negatively affects the results of transplantation and therefore should be considered as an indication for retransplantation. Reversible and persistent variants of late liver allograft dysfunction have favorable) prognosis. If the etiology of late dysfunction is not established, the regular surveillance with monitoring for fibrosis and repeated attempts to clarify the diagnosis should be continued.

Features of the management of patients with biliary dysfunctions with spasm of the sphincter of Oddi

The aim. Assessment of clinical manifestations of biliary dysfunction, duodenal hypertension. The analysis of data on the effect of drugs of various pharmacological groups on the motor function of the gallbladder is carried out.Materials and methods. We were examined 60 patients (18–50 years old, mean age 41±4.6 years), mostly women (44). All patients underwent a general clinical examination, including blood and urine tests, biochemical blood parameters, ultrasound examination of the abdominal organs and monitoring of gallbladder contractility, esophagogastroduodenoscopy. The examined patients were divided into 2 groups of 30 patients.Results and conclusion. The use of choleretics for spasm of the sphincter of Oddi and symptoms of duodenal hypertension is not always justified. The leading link in the treatment of this type of biliary dysfunction are antispasmodics, which eliminate spasm of the sphincter zones, which restores the passage of bile through the biliary tract and reduces the phenomena of biliary insufficiency. Mebeverine hydrochloride also eliminates the phenomena of duodenal hypertension, which facilitates the removal of bile from the biliary tract. When choleretics are prescribed for the treatment of patients with biliary dysfunction with spasm of the sphincter of Oddi, it is quite possible that the course of this pathology will worsen.

Using artificial intelligence to predict choledocholithiasis: can machine learning models abate the use of MRCP in patients with biliary dysfunction?

Prompt diagnosis of choledocholithiasis is crucial for reducing disease severity, preventing complications and minimizing length of stay. Magnetic resonance cholangiopancreatography (MRCP) is commonly used to evaluate patients with suspected choledocholithiasis but is expensive and may delay definitive intervention. To optimize patient care and resource utilization, we have developed five machine learning models that predict a patients' risk of choledocholithiasis based on clinical presentation and pre-MRCP investigation results. Inpatients admitted to the Royal Hobart Hospital from 2018 to 2023 with a suspicion of choledocholithiasis were included. Exclusion criteria included prior hepatobiliary surgery, known hepatobiliary disease, or incomplete records. Variables related to clinical presentation, laboratory testing, and sonographic or CT imaging were collected. Four machine learning techniques were employed: logistic regression, XGBoost, random forest, and K-nearest neighbours. The three best performing models were combined to create an ensemble model. Model performance was compared against the American Society for Gastrointestinal Endoscopy (ASGE) choledocholithiasis risk stratification guidelines. Of the 222 patients included, 113 (50.9%) had choledocholithiasis. The most successful models were the random forest (accuracy: 0.79, AUROC: 0.83) and ensemble (accuracy and AUROC: 0.81). Every model outperformed the ASGE guidelines. Key variables influencing the models' predictions included common bile duct diameter, lipase, imaging evidence of cholelithiasis, and liver function tests. Machine learning models can accurately assess a patient's risk of choledocholithiasis and could assist in identifying patients who could forgo an MRCP and proceed directly to intervention. Ongoing validation on prospective data is necessary to refine their accuracy and clinical utility.

Assessment of the clinical effectiveness of use of hymecromone in combination with ursodeoxycholic acid in biliary pathology

The article presents the results of a clinical evaluation of the comparative effectiveness of monotherapy with urosodeoxycholic acid and its combination with himecromone at dosages of 600 mg and 1200 mg in 368 patients with biliary pathology. The study revealed a significant improvement in the indicators of the majority of patients in the observed groups (84.7% in the UDCA group, 85.9% in the UDCA + Gimecromone 600 mg group, 87.9% in the UDCA + Gimecromone 1200 mg group). Evaluation of the effectiveness of gimecromone at a dosage of 600 mg/day and 1200 mg/day in combination with UDCA showed that the relief of symptoms of biliary dysfunction had a dose-dependent effect and the use of gimecromone at a dose of 1200 mg /day had a more pronounced clinical effect.

Probable gastrointestinal disease factors in postmenopausal age women receiving antihypertensive therapy

The frequency of achieving control as a result of taking antihypertensive drugs in women in the age group 55-64 years reaches 78.9%, the frequency of gastrointestinal symptoms occurring during treatment of hypertension is up to 62%. The aim: to analyze the probable causes of the development of symptoms of diseases of the gastrointestinal tract in postmenopausal patients receiving antihypertensive therapy. Material and methods. A comprehensive clinical examination of out-patient and in-patient patients of health care institutions of the Smolensk region with hypertension aged 50 to 84 years, (group AG, n=160) mean age 67.4 ± 17.4 years. Results. Complex examination and observation on the basis of standard methods with high probability shows the formation of gastroesophageal reflux disease, gastritis, simple erosions of the gastric mucosa, biliary dysfunction, chronic pancreatitis steatohepatosis in the observed patients. Conclusions: In postmenopausal women receiving antihypertensive therapy, there are major gastrointestinal symptoms of varying severity, arising in conditions of irrational nutrition, psycho-emotional and physical stress on the background of irregular medication. Based on the analysis of modern scientific sources, it can be argued that complex rational antihypertensive, antiplatelet, hypolipidemic, antisecretory and eradication therapy and the correction of modifiable risk factors ensures the achievement of remission of gastrointestinal and cardiovascular disease in the optimal time, improves the quality, life expectancy of patients and improves disease prognosis.

Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention.

The COVID-19 pandemic has had a profound impact on global health, necessitating a comprehensive understanding of its diverse manifestations. Cholangiopathy, a condition characterized by biliary dysfunction, has emerged as a significant complication in COVID-19 patients. In this review, we report the epidemiology of COVID-19, describe the hepatotropism of SARS-CoV-2, and present the histopathology of acute liver injury (ALI) in COVID-19. Additionally, we explore the relationship between pre-existing chronic liver disease and COVID-19, shedding light on the increased susceptibility of these individuals to develop cholangiopathy. Through an in-depth analysis of cholangiopathy in COVID-19 patients, we elucidate its clinical manifestations, diagnostic criteria, and underlying pathogenesis involving inflammation, immune dysregulation, and vascular changes. Furthermore, we provide a summary of studies investigating post-COVID-19 cholangiopathy, highlighting the long-term effects and potential management strategies for this condition, and discussing opportunities for intervention, including therapeutic targets, diagnostic advancements, supportive care, and future research needs.

Assessing risks of hepatobiliary disorders in children under combined exposure to persisting herpes and technogenic chemicals

Chronic persistent viral infection leads to developing immune deficiency and may induce lesions in many organs, the hepatobiliary system included. This, in its turn, may facilitate the onset of diseases of the digestive system under exposure to technogenic chemicals, especially those able to produce hepatotoxic effects. In this study, our aim was to examine risks of developing hepatobiliary disorders in children under combined exposure to persisting herpes infection and technogenic chemicals. We conducted a clinical examination of 324 children aged between 6 and 17 years living either in a large industrial city or on a territory where the sanitary-hygienic situation was favorable. The examination included a clinical checkup, laboratory diagnostic tests identifying herpes markers, chemical analyses aimed at establishing levels of technogenic chemicals in blood, and ultrasound scanning of hepatobiliary organs. We established that exposure to airborne technogenic chemicals created elevated levels of aromatic hydrocarbons and formaldehyde in 64.9–97.6 % of the exposed children; elevated manganese and chromium levels, in 20.8–34.6 % of them. Markers of cytomegalovirus (CMV) and Epstein Barr virus (EBV) were detected in 75 % of the exposed children; each second child had HSV-1 or HSV-2; each third child had human herpesvirus 6. Hepatobiliary disorders occurring under combined exposure to persistent herpes and echnogenic chemicals were represented by structural liver changes in 30.8 % of the examined children; abnormally shaped gallbladder or reactive changes in its walls and dyscholia, in 15.7–48.8 %. These disorders entail elevated levels of direct bilirubin and greater ALT against imbalance of oxidant and antioxidant systems and manifest themselves as biliary pathology in 69.5 % of cases. Exposed children with persistent herpes infection have 1.2–2.3 times higher likelihood of developing structural changes in the liver and gallbladder pathology and up to 4.3 times higher risks of biliary dysfunction and chronic gastroduodenitis.

PostCOVID biliary dysfunctions: causes and treatment

The novel coronavirus infection (COVID-19) is accompanied, among others, by the damage of the digestive system, in particular, the formation of biliary dysfunctions. The article presents the data of observation and treatment of patients with post-covid phenomena of biliary insufficiency.

КЛИНИЧЕСКАЯ ОЦЕНКА ЭФФЕКТИВНОСТИ ТЕРАПИИ СОПРОВОЖДЕНИЯ ПРИ ОРТОДОНТИЧЕСКОМ ЛЕЧЕНИИ ПОДРОСТКОВ С ХРОНИЧЕСКИМИ ЗАБОЛЕВАНИЯМИ ВЕРХНИХ ОТДЕЛОВ ЖЕЛУДОЧНО-КИШЕЧНОГО ТРАКТА

The aim of the work is to provide a clinical assessment of the efficacy of therapy for accompanying orthodontic treatment of adolescents with chronic diseases of the upper part gastrointestinal tract. Material and methods. There were 109 adolescents at the age of 12–15 years with dental anomalies and gastroduodenal pathology (chronic gastritis, chronic gastroduodenitis, biliary dysfunction) were taken for orthodontic treatment. The state of oral hygiene, periodontal tissues and hard tooth tissues in the dynamics of orthodontic treatment was evaluated. We used the Silness-Loe and Stallard hygiene indexes, periodontal indexes – PMA, stomatorrhagia, Schiller-Pisarev, dental calculus, and calculated the reduction of caries.&#x0D; Results. Phased application of accompanying therapy (a calcium preparation with vitamin D3 and trace elements (Calcemin), magnesium (Magne B6), an immunostimulating drug of bacterial origin (Imudon) for the orthodontic treatment of adolescents with chronic pathology of the digestive tract shows an anti-inflammatory and caries static effect.

Combined endoscopic mAnagement of BiliaRy and gastrIc OutLET obstruction (CABRIOLET Study): A multicenter retrospective analysis.

ObjectivesCombined biliary obstruction and gastric outlet obstruction (GOO) represent a challenging clinical scenario despite developments in therapeutic endoscopic ultrasonography (EUS) as GOO might impair EUS‐guided biliary drainage. Little is known about the effectiveness of different therapeutic combinations used to treat double obstruction, especially regarding stent patency.MethodsAll consecutive patients with double obstruction treated between 2016 and 2021 in three tertiary academic centres were eligible for inclusion. Five combinations involving enteral stenting (ES), EUS‐guided gastroenterostomy (EUS‐GE), hepaticogastrostomy (EUS‐HGS), choledochoduodenostomy (EUS‐CDS), and transpapillary biliary stenting (TPS) were evaluated for dysfunction during follow‐up, either as proportions or dysfunction‐free survival (DFS) using Kaplan–Meier estimates.ResultsNinety‐three patients were included (male 46%; age 67 [interquartile range 60–76] years; pancreatic cancer 73%, metastatic 57%), resulting in 103 procedure combinations. Different combinations showed significantly different overall dysfunction rates (p = 0.009), ranging from the null rate of EUS‐GE+HG to the 18% rate of EUS‐GE+TPS, 31% of EUS‐GE+EUS‐CD, 53% of ES+TPS and 83% of ES+EUS‐CDS. Sub‐analyses restricted to biliary dysfunction confirmed these trends. A multivariate Cox proportional‐hazards regression of DFS, a stenosis distal to the papilla (HR 3.2 [1.5–6.9]) and ES+EUS‐CDS (HR 5.6 [2–15.7]) independently predicted dysfunction.ConclusionsDespite a lack of statistical power per combination, this study introduces new associations beyond the increased risk of GOO recurrence with ES versus EUS‐GE. EUS‐CDS showed reduced effectiveness and frequent dysfunction in the context of GOO, especially when combined with ES. EUS‐GE+HGS or EUS‐GE+TPS in this setting might result in superior patency. These results suggest that a prospective evaluation of the optimal endoscopic approach to malignant double obstruction is needed.

A Novel Murine Model for Studying Alcohol‐associated Biliary Dysfunction

Alcoholic hepatitis (AH) is a severe, potentially life‐threatening form of alcohol‐associated liver disease (ALD) with limited therapeutic options. Existing evidence indicates that cholestasis and biliary dysfunction are common in AH patients and can worsen the prognosis. However, most ALD murine models used today can only recapitulate hepatic steatosis with limited features of AH, which significantly curbs research related to ALD pathogenesis. To develop a murine model that is feasible and less time‐consuming, we included a subtoxic dose of α‐naphthylisothiocyanate (ANIT), a well‐studied intrahepatic cholestasis inducer, in an alcohol feeding model, as a second hit. Mice were fed with an ethanol diet (EtOH) for 10 days or 4 weeks, followed by ANIT administration 48 hours before sample collection. Our results showed that ANIT did not cause overt liver injury in pair‐fed mice, but an observable increase in serum levels of AST in mice fed EtOH for 10 days. Remarkably, in the 4‐week ALD model, serum levels of ALT, AST, total bile acids (TBA), and hepatic levels of TBA were all significantly increased in mice given EtOH and ANIT, indicating a synergistic effect of EtOH and ANIT on liver injury that is dependent on EtOH feeding. In the liver, 4‐week EtOH‐fed mice displayed cholangitis, lytic cell death, and neutrophil infiltration around the periportal area following ANIT treatment as shown by H&amp;E and LY6G staining. In contrast, pair‐fed mice did not show abnormal liver histology following ANIT treatment. Expression of several inflammation‐related genes that are increased in livers from AH patients were analyzed. Consistent with histological observations, hepatic expression of genes like Cxcl1, Ccl2, Ccl20, and Lcn2 were significantly increased in 4‐week EtOH‐fed mice following ANIT treatment, suggesting that ANIT synergistically enhanced EtOH‐induced immune response in the liver. Taken together, our results suggest that EtOH‐dependent changes in the liver can cause higher susceptibility to biliary injury and that a subtoxic dose of ANIT pushes alcohol‐associated liver damage towards a more severe phenotype in mice. Overall, our results support a treatment scheme for alcohol‐associated cholestasis that is feasible, less time‐consuming, cost‐effective, and with modulable severity of phenotypes.

Особливості клінічної симптоматики у хворих на гастроезофагеальну рефлюксну хворобу при поєднанні з дисфункцією сфінктера Одді

Стаття присвячена вивченню особливостей клінічної симптоматики в пацієнтів із поєднаними захворюваннями — гастроезофагеальною рефлюксною хворобою та дисфункцією сфінктера Одді (СфО). Дослідження проведено на 78 пацієнтах, які були розподілені на три групи залежно від характеру дисфункції сфінктера Одді. Такий підхід дозволив зробити низку важливих висновків, які свідчать про обтяжливий вплив дисфунції жовчовивідних шляхів на перебіг гастроезофагеальної рефлюксної хвороби незалежно від форми дисфункції, що підтверджується зростанням частоти та інтенсивності основних симптомів дис-пептичного та больового синдромів.

Specifics of functional activity of the immune system, carbohydrate and lipid metabolism in overweight and obese children with biliary dysfunction

Objective — to evaluate functional activity of the immune system, carbohydrate and lipid metabolism in children with biliary dysfunction against the background of overweight and obesity.&#x0D; Materials and methods. At the SI «Institute Gastroenterology of the National Academy of Medical Sciences of Ukraine» observations were performed on 108 children with the mean age 12.5 ± 2.51 years. Based on the results of investigation of motor and evacuator gallbladder (GB) function and body mass index, the pediatric patients were divided into three groups: group I included 52 overweight children with gallbladder hypofunction and obesity; group II consisted of 42 overweight children with normal gallbladder function and obesity; group III (comparison group) included 14 children with normal weight and biliary normokinesia. Investigations included anthropometric measurements and ultrasound imaging of the abdomen. ELISA was used to determine blood serum levels of insulin, interleukin‑6 (IL), IL‑10, tumour necrosis factor‑a (TNF‑a).&#x0D; Results. The following augmentation of the median levels was established when compared with group III: IL‑6 in 2.2 times (p &lt; 0.05) and TNF‑a in 4.5 times (p &lt; 0.05) in patients of group I, levels of IL‑6 in 2.3 times (p &lt; 0.05) and TNF‑a in 4.3 times (p &lt; 0.05) in patients of group II. The IL‑10 level in group I patients was lower in 2.5 times than in group II patients (p &lt; 0.05), and in 4.4 times vs group III patients (p &lt; 0.05). The serum insulin levels in children of groups I and II were in 2.2 times (p &lt; 0.05) and 1.5 times (p &lt; 0.05) lower, and HOMA‑IR index in 2.3 times (p &lt; 0.05) and in 1.8 times (p &lt; 0.05), respectively, in comparison with group III patients. The following blood serum levels vs group III were established: triglycerides (TG) increased in group I in 1.4 times (p &lt; 0.001) and in group II in 1.5 times (p &lt; 0.001); low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were increased both in I and II groups in 1.2 times, (p &lt; 0.01) and 1.5 times, (p &lt; 0.001), respectively. The atherogenic index (AI) raised in 1.6 times (p &lt; 0.001) in group I patients and in 1.5 times (p &lt; 0.05) in group II patients compared to group III, whereas high density lipoprotein (HDL) levels were decreased in the I and II groups in 1.2 times (p &lt; 0.01) in comparison with group III patients.&#x0D; Conclusions. Regardless of the gallbladder functional state in overweight and obese pediatric patients, the abnormalities of the immune system indices have been established and, consequently, carbohydrate metabolism disorders (increased levels of insulin and index HOMA‑IR). The lipid metabolism disturbances have been established in the overweight and obese children with gallbladder hypofunction (significant increase in the levels of TG, LDL, VLDL, AI and decreased HDL levels). Correlation analysis in the groups of overweight and obese children with gallbladder hypofunction showed the presence of significant relationships between biliary sludge and IL‑6, TNF‑a levels, gallbladder volume and insulin and glucose levels, gallbladder hypofunction and levels of total cholesterol, HDL, LDL and as well as between the gallbladder dimensions and atherogenic index.&#x0D;

Liver diseases at new coronavirus infection in pregnant women of Samara region

The new coronavirus infection (COVID-19) is a life-threatening condition. The features of the treatment of COVID-19 in pregnant women are not sufficiently studied and contradictory, therefore, research in this area is relevant.Objective. Assess the presence of liver disease in pregnant women with COVID-19 infection during pregnancy and after childbirth, taking into account the treatment.Methods. A retrospective analysis of medical records of 43 pregnant women aged 19 to 39 years (mean age 29.1 ± 5.4 years) who were hospitalized with laboratory-confirmed COVID-19 infection was performed. The selection was carried out by the method of continuous sampling.Results. 17 women (39.5%) had an acute respiratory viral disease, 26 people (60.5%) were diagnosed with bilateral polysegmental pneumonia with pulmonary tissue damage from 5 to 25%. In the structure of extragenital pathology, 46.5% of women had anemia and 23.3% of diseases of the hepatobiliary system, including chronic non-calculous cholecystitis (4.7%), biliary dysfunction (7%), chronic viral hepatitis B (2.3%) and chronic viral hepatitis C (9.3%). 6.9% were diagnosed with cholestatic hepatosis of pregnant women before admission to the hospital. An increase in the level of transaminases above the upper normal values was noted in 69.8% of cases, alkaline phosphatase – in 76.7%. In the structure of pregnancy complications in women with COVID-19 infection, fetal hypoxia prevailed in 15 women (34.9%). In second place is premature rupture of amniotic fluid (16.3%) and fetal malnutrition (16.3%).Conclusions. Pregnant women with diseases of the hepatobiliary system and anemia are most susceptible to new coronavirus infection. They have an increase in the level of transaminases and alkaline phosphatase, which can be caused by liver damage due to the increased tropism of the virus to cholangiocytes and hepatocytes, as well as hepatotoxic drugs. The most common complications of pregnancy in women with a new infection are premature birth, fetal hypoxia, and antenatal death.

Стан панкреатобіліарної системи та інтестинальної мікрофлори в дітей із неалкогольною жировою хворобою печінки

Неалкогольна жирова хвороба печінки (НАЖХП) об’єднує такі патологічні стани, як стеатоз печінки, неалкогольний стеатогепатит, фіброз та цироз печінки, і вважається печінковим проявом метаболічного синдрому. Не лише печінка стає органом-мішенню в разі формування метаболічного синдрому: доведена можливість розвитку стеатозу жовчного міхура, підшлункової залози та біліарного тракту. Жирова інфільтрація панкреатобіліарного тракту асоційована з порушенням процесів травлення, що супроводжується розвитком дисбіотичних змін та інтестинальних розладів. Зміни кишкової мікробіоти, зі свого боку, можуть індукувати системну запальну реакцію та сприяти прогресуванню НАЖХП. Мета: вивчити структурно-функціональний стан панкреатобіліарної системи та зміни тонкокишечної мікрофлори в дітей із НАЖХП. Методи. У 34 дітей із патологією шлунково-кишкового тракту визначали контрольований параметр ультразвукового затухання із використанням апарата FibroScan. Оцінку функціонального стану біліарного тракту здійснювали за допомогою ультразвукового дослідження органів черевної порожнини із пробним сніданком для визначення скоротливої функції жовчного міхура й тонусу сфінктера Одді. Для характеристики стану тонкокишкової мікробіоти проводили водневий дихальний тест із навантаженням глюкозою або лактозою. Розподіл дітей на групи відбувався згідно з даними транзієнтної еластрографії печінки (FibroScan): контрольну групу становив 21 пацієнт без стеатозу печінки, основну групу — 13 пацієнтів із стеатозом печінки. Результати. Діти з неалкогольною жировою хворобою печінки мали ознаки ураження не тільки печінки, але й жовчовивідних шляхів та підшлункової залози. Патологія жовчовивідних шляхів у пацієнтів із НАЖХП частіше проявлялась у вигляді гіпотонії сфінктера Одді та гіпокінезії жовчного міхура. Ураження підшлункової залози в дітей із НАЖХП може пояснюватися наявністю функціонального розладу сфінктера Одді та проявами стеатозу підшлункової залози. Зміни в стані мікрофлори тонкої кишки спостерігалися у 27,6 % обстежених хворих. Синдром надмірного бактеріального росту вірогідно частіше відмічався в групі хворих зі стеатозом печінки.

Частота залучення в патологічний процес різних відділів шлунково-кишкового тракту в дітей із біліарною дисфункцією

The close anatomical and physiological connection of the digestive organs leads to a significant spread of functional disorders in various diseases. Purpose — to investigate the frequency and features of the clinical course of biliary dysfunction (BD) in children. Materials and methods. 66 children aged 10–18 years with BD were examined. The study included a complete clinical examination of children, laboratory and instrumental methods. To assess the severity of clinical symptoms in the examined patients was used traditional score scale of symptoms (0–3 points) and the frequency index (FI). Results. In most children, the database was combined with other functional and organic lesions of the digestive tract (n=56, 84.8%). The database was most often combined with chronic gastritis and duodenitis, as well as with functional motor disorders. FI in children with BD involved in the pathological process of the stomach and duodenum was the highest (0.59), and IR in children with BD and intestinal involvement was the lowest (0.23). The relationship between the frequency of combined pathology and the frequency of cases of increase in the size of the gallbladder (χ2=22.87 at a critical value of χ2=9.33 for the significance level p&lt;0.01). Hyper- or hypofunctions of the biliary tract occurred with the same frequency. Conclusions. Biliary dysfunction in children is significantly more often combined with chronic gastritis and duodenitis, as well as with other functional disorders of the gastrointestinal tract (duodenogastric reflux). In children with biliary dysfunction and involvement in the pathological process of other parts of the gastrointestinal tract there is an increase in the frequency of exacerbations, more pronounced signs of dyspeptic syndrome on the background of pain with the same intensity and more often ultrasound reveals signs of gallbladder dysformation. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: children, biliary dysfunction.