Hymecromone Administration in Real Clinical Practice: Results of the Prospective Multicentre Observational Study in the Republic of Kazakhstan

Introduction. This multicentre prospective non-interventional observational study was conducted to obtain additional data about Odeston efficacy and safety in routine clinical practice. The objectives of the study included collection of clinical characteristics of patients, evaluation of Odeston effects in treatment of biliary pain and changes in the gallbladder emptying, evaluation of compliance to therapy, and treatment effect satisfaction.Materials and methods. The study was conducted from July 2020 to April 2021 at the premises of 60 study sites in 4 cities of the Republic of Kazakhstan. Patients having indications for Odeston administration according to the patient leaflet were enrolled. The study included 2 patient visits and an intermediate telephone contact. A visual analogue scale and RAPID questionnaire were used to characterise biliary pain; severity of associated symptoms, bowel habit and a quality of life according the SF-12 were also assessed. A rate of a ≥50 % reduction in symptom severity was used as a primary efficacy criterion; a rate of a ≥10 improvement in the SF-12 quality of life score was used as a secondary efficacy criterion. Compliance to treatment was evaluated using a number of days on Odeston. Treatment satisfaction was assessed using 5 grades.Results. 877 patients, 68.2 % of females and 31.8 % of males, were included in the study; the mean age was 46.0 ± 14.9 years. Primary functional biliary disorder was diagnosed in 65.3 % of patients, chronic non-calculous cholecystitis — 51.4 %, uncomplicated gallbladder disease — in 8.9 %, biliary sludge — 38.4 %, sphincter of Oddi functional disorder — 5.3 % of patients. A dose of Odeston was prescribed at the discretion of the physician. Group A patients received 600 mg (n = 89), group B received 1200 mg of Odeston a day (n = 788). In group B, an incidence of pronounced pain interference with daily living activities was higher. In both groups, the mean VAS scores were reduced to 1 point on treatment, a primary efficacy criterion was achieved in 77.3 % of patients in group A and in 79.8 % of patients in group B, р < 0.05. In both groups, a reduction in the incidence of constipation and diarrhea (р < 0,001) and an increase in the mean scores of physical and mental functioning were noted (р < 0.001, though a secondary efficacy criterion was not achieved (a ≥10 change in the SF-12 score). A prevalence of ultrasonographic sings of biliary sludge was reduced, and an increased gallbladder emptying was observed (p < 0.001). 77.4 % of patients in a total group of patients reported about drug administration for 21 days. A number of patients who were completely satisfied with treatment was higher in group B (p = 0.027).Conclusions. It was found that biliary pain interfered with daily living activities and commonly accompanied by other symptoms of gastrointestinal dysmotility. Odeston effectively reduces the severity of biliary pain, corrects dyspeptic disorders and normalizes stool pattern in patients with functional and organic diseases of the biliary system. Treatment satisfaction was higher with a dose of 1200 mg a day, particularly in more pronounced interference of pain with daily living activities.

Efficacy of Hymecromone in Post-Cholecystectomy Patients

Background. The cholecystectomy is the major cause of sphincter of Oddi dysfunction (SOD), that may be classified as post-cholecystectomy syndrome (PCES). Treatment of PCES requires in most of the cases application of selective antispasmodic drugs.Aim. To evaluate efficacy and safety of hymecromone in patients with post-cholecystectomy SOD, to compare standard and reduced doses of hymecromone.Methods. Overall, 26 patients were enrolled in non-interventional comparative study: 2 males, 24 females, aged from 25 to 74 years. All patients underwent cholecystectomy for symptomatic gallstone disease within 1 to 10 years prior to beginning of the study. All patients were diagnosed to have SOD according to Rome IV Diagnostic Criteria for functional biliary sphincter of Oddi disorder (E1b). All patients underwent hymecromone monotherapy for 3 weeks. Patients were randomized to group A and B to receive full-dose or half-dose of the drug respectively.Results. Abdominal pain completely subsided in 85 % of patients, significant improvement was found for bloating and diarrhea. Mild increase in fasting common bile duct (CBD) diameter after treatment (7.23 ± 0.99 vs 6.78 ± 1.01; p = 0.029) was attributed to choleretic action of hymecromone. Hymecromone resulted in significant improvement of CBD response to fatty meal stimulation (ΔCBD): –1.08 ± 0.46 mm vs –0.10 ± 0.33 mm pretreatment (p = 0.016). Degree of improvement was more pronounced in the group A (full-dose) as compared to group B (half-dose) for abdominal pain (Z = 2.74, p = 0.031), bloating (Z = 2.63, p = 0.035) and constipation (Z = 2.61, p = 0.038)Conclusion. Hymecromone demonstrated itself to be an effective and safe drug, that may be applied both in standard and half dose. However, the efficacy of full-dose is higher both for the treatment of biliary pain and dyspeptic symptoms. Transabdominal ultrasound may be applied as a reliable test for both prediction of treatment efficacy and to monitor patients state during treatment course.

Mass-Like Extreme Wall Thickening of the Entire Common Bile Duct in a Case of Portal Cavernoma Cholangiopathy

Portal cavernoma cholangiopathy (PCC) refers to the cholangiographic abnormalities that occur in patients with portal cavernoma. These abnormalities may be either due to chronic portal vein thrombosis or extrahepatic portal vein occlusion. These abnormalities occur due to enlargement of the bridging tortuous paracholedochal, epicholedochal, and cholecystic veins exerting pressure on the bile ducts. Ischemic changes can also occur in the bile duct due to portal vein thrombosis, which affects the microvascular circulation or associated hepatic artery thrombosis. These may be either reversible with shunt procedures such as transjugular intrahepatic portosystemic shunt (TIPS) or irreversible in the advanced stage, leading to recurrent episodes of biliary pain, cholangitis, and cholestasis. Occasionally it may present as mass-like diffuse common bile duct (CBD) wall thickening, which may be confused with mimickers like primary CBD lymphoma, immunoglobulin G4-related sclerosing cholangitis, and even cholangiocarcinoma on imaging. Thus, we need to be aware of the mass-forming PCC imaging findings to avoid unnecessary invasive procedures like biopsy or surgical intervention. Here, we present a case of PCC, which presented as mass-like diffuse CBD wall thickening with patent lumen on ultrasound that led to further workup with contrast-enhanced computed tomography and magnetic resonance imaging. The wall thickening showed persistent delayed enhancement, no significant diffusion restriction, and there was also associated superior mesenteric vein thrombosis with multiple mesenteric collaterals. A positron emission tomography-CT scan also ruled out malignant disease as there was no uptake. Finally, a diagnosis of mass-forming PCC was made by combining imaging features and excluding other causes.

The biliary continuum: an up-to-date look at biliary tract diseases

In the structure of gastrointestinal diseases, the pathology of the hepatobiliary system currently ranks second in frequency of occurrence. The stages of diseases of the biliary system can be combined into the so-called “biliary continuum”, when one patient has a consistent development of pathogenetically related diseases of the biliary tract. The progressive course of functional motility disorders of the biliary tract gradually leads to the development of organic pathology, including chronic cholecystitis, the subsequent development of gallstone disease and possible postcholecystectomy complications. Among the diseases of the biliary system, one of the most frequently used diagnoses is chronic cholecystitis. The development of chronic cholecystitis is associated with repeated attacks of acute inflammation or prolonged irritation of large gallstones. The clinical aspects of chronic cholecystitis and other pathologies included in the the «biliary continuum» largely depends on concomitant dyskinesia. There are several directions for the treatment of pathologies of the biliary system: diet therapy, medication, endoscopic and surgical treatment. According to the latest guidelines, the most important direction in modern therapy of diseases of the biliary system is the restoration of the motility of the biliary tract and the normalization of the physicochemical properties of bile. The central place in the treatment of diseases of the “biliary continuum” is given to antispasmodic drugs. The administration of antispasmodics is recommended in order to relieve biliary pain and dyspeptic symptoms caused by spasm of smooth muscles, as well as to control the inflammatory process due to a decrease in the release of pro-inflammatory substances. This article describes in detail the importance of the recovery of the biliary tract motor activity and the improvement of the physico-chemical properties of bile acids.

Efficacy of trimebutine in the treatment of functional gastrointestinal disorders: an observational multicenter study

Aim. Evaluation of the practice of using trimebutine (tablets, 300 mg, extended release), for the treatment of patients with functional gastrointestinal disorders (FGID) in primary health care. Materials and methods. A prospective observational multicenter non-interventional study was carried out, which included patients of both sexes aged 18 to 60 years with a verified diagnosis of functional gastrointestinal disorders (functional dyspepsia, irritable bowel syndrome, biliary tract dysfunction, sphincter of Oddi dysfunction, postcholecystectomy syndrome). Trimebutine was prescribed in accordance with the instructions for medical use: orally, 300 mg twice per day for 28 days. The severity of simptoms was evaluated by five-point rating scale. Results. The study included 4433 patients, the per protocol sample consisted of 3831 people. The proportion of patients with a significant decrease in the severity of abdominal pain after treatment was 74.73% (95% confidence interval CI 73.3276.11). At the and of the study a statistically significant decrease in the severity of FGID` simptoms was observed: epigastric pain/burning (mean score at the 1st visit was 1.21 [95% CI 1.181.25], at the 2nd visit 0.22 [95% CI 0.20.23]; p0.001), abdominal pain (1st visit 2.01 [95% CI 1.982.04), 2nd visit 0.33 [95% CI 0.310.35]; p0.001), biliary pain (1st visit 1.22 [95% CI 1.181.26], 2nd visit 0.2 [95% CI 0.190.22]; p0.001), postprandial fullness and early satiation (1st visit 1.29 [95% CI 1.251.32], 2nd visit 0.21 [95% CI 0.190.22]; p0.001), severity of heartburn (1st visit 0.92 [95% CI 0.880.95], 2nd visit 0.18 [95% CI 0.170.20]; p0.001), belching (1st visit 1.13 [95% CI 1.091.16], 2nd visit 0.22 [95% CI 0.210.24]; p0.001), as well as abdominal distention (1st visit 1.99 (95% CI 1, 96, 2.03), 2nd visit 0.43 [95% CI 0.410.45]; p0.001). Conclusion. The present prospective observational multicenter non-interventional study has demonstrated that trimebutine is an effective approach to treating FGID.

Dysfunction of Sphincter of Oddi

Sphincter of Oddi Dysfunction (SOD) is a smooth muscle valve disorder regulating the flow of biliary and pancreatic secretions into the duodenum. SOD is categorized into three different types based on the Milwaukee classification system, with a prevalence of 1.5% in the general population. Type I patients have pain as well as abnormal liver enzymes and a dilated common bile duct. Type II SOD consists of pain and only one objective finding, and Type III consists of biliary pain only. The link between SOD and dyslipidemia is underappreciated. Increased biliary absorption of cholesterol in the form of biliary salts can increase the excretion and ultimately result in decreased serum cholesterol levels. It is important to consider SOD in patients with pain, elevated LFT’s and dyslipidemia despite statin therapy. In this article, a case of Type I SOD with recurrent pancreatitis is reviewed. This patient was initially diagnosed with acute pancreatitis secondary to hypertriglyceridemia. He had an additional episode of pancreatitis despite being on statin therapy with an improvement of triglycerides. SOD was then diagnosed with sphincterotomy after his second admission to the hospital. This resulted in the resolution of the patient’s symptoms and improvement of LFT’S. Manometry has long been considered the gold standard for diagnosis; however, it is not always available in low-resource settings. Therefore, endoscopic sphincterotomy is being considered for diagnosis as it can be diagnostic and therapeutic.

Chronic acalculous cholecystitis and biliary dysfunction: how does clinical diagnosis affect management?

Similar abdominal pain of biliary type in functional disorders of biliary tract and chronic acalculous cholecystitis causes objective difficulties to differentiate not only between each other, but also with other diseases of gastrointestinal tract. The clinical picture is so homogeneous and difficult to distinguish from cholelithiasis that some patients undergo unreasonable surgical interventions for CAC and FDBT. Individual publications pushing for such an aggressive strategy are sporadic and need to be clarified in larger studies. The first choice drugs for treatment of FDBT are spasmolytics; ursodeoxycholic acid drugs are used as adjuvant agents. In CAC, the initial therapy will be similar, but the treatment regimen can be expanded with targeted etiotropic (if the cause of cholecystitis is identified – giardiasis, opisthorchiasis, etc.) or empirical antimicrobial/antiparasitic therapy. The greatest interest today is caused by hymecromone – a drug with proven by both experimental and controlled studies combined choleretic, selective spasmolytic action, mediated effect of reducing bile lithogenicity and possible anti-inflammatory action. Hymecromone effectively relieves biliary pain without causing gallbladder contractions, which determines the possibility of its wide application both in CAC and FDBT, both in monotherapy and in combination with other agents, primarily with UDCA. In this article the issues of optimization of diagnostic and therapeutic strategy of management of patients with biliary pain to avoid unreasonable cholecystectomies in acalculous diseases of the biliary tract are considered.

Possibilities of combined therapy in patients with functional biliary sphincter of Oddi disorder

Introduction. The prevalence of functional biliary disorders continues to increase with insufficient effectiveness of existing treatment approaches. Among them, functional biliary disorders of sphincter of Oddi account for at least 50%.Objective. To study efficacy, safety and tolerability of a fixed combination of glycyrrhizic acid and ursodeoxycholic acid (Fosfogliv Urso) in capsule form in patients with functional biliary disorders of sphincter of Oddi.Materials and Methods. The study included 32 patients diagnosed with functional biliary sphincter of Oddi disorders established according to the Rome Criteria IV revision (2016). Patients received Fosfogliv Urso (250 mg ursodeoxycholic acid and 35 mg glycyrrhizic acid) 1 capsule 3 times a day for 8 weeks. Prior to treatment, all study participants underwent a standard set of laboratory and instrumental examinations.Results. Against the background of Fosfogliv Urso treatment, statistically significant decrease of biliary pain prevalence up to 48.3% (p < 0.001); intense biliary pain up to 11.4% (p < 0.0001); intensity of pain syndrome on visual analogue scale down to 1.7 ± 0.9 cm was registered (p < 0.0001). Alanine aminotransferase activity significantly decreased to 34.0 ± 4.0 U/L (p < 0.001). There was a tendency of choledochal diameter decrease to 0.57 ± 0.01 cm. Treatment efficacy was rated by patients as very good and good in 83.4% of cases. The safety profile was assessed as favorable and tolerability as satisfactory.Discussion. The results obtained were superior to those previously obtained for ursodeoxycholic acid monotherapy and confirmed the data of the previously conducted phase III study. The rationality of the combination is due to the mutual complementation and possible synergism of the pharmacological effects of glycyrrhizinic and ursodeoxycholic acids.Conclusion. The results obtained allow to recommend the prescription of Fosfogliv Urso in the complex scheme of treatment and prophylaxis of functional biliary disorders of sphincter of Oddi.

A CRITICAL EVALUATION OF CLINICOPATHOLOGICAL STUDY ON LIVER FUNCTIONS IN POSTCHOLECYSTECTOMY CASES COMPARED TO PREOPERATIVE STATUS

INTRODUCTION: Gallstones [cholelithiasis] are the most common biliary pathology. It is estimated that gallstones affect 10-15% of the population in Western societies. They are asymptomatic in majority of cases (780). In the UK, the prevalence of gallstones at the time of death is estimated to be 17% and may be increasing. Approximately 1-2% of asymptomatic patients will develop symptoms requiring surgery per year, making cholecystectomy one of the most common operations performed by general surgeon. Gallstones are quite common in the general populations and women are affected more often in the ratio of 4:1. AIMS AND OBJECTIVES: Assessment of hepatic status in pre- operative patients in comparison with postoperative patients. Comparative evaluations of derangement of hepatic parameters in the preoperative period of patient undergoing different forms of gallbladder operations (conventional or laparoscopic cholecystectomy). To evaluate the usual time required for return of deranged hepatic function, if any, to normal levels. To analyse the outcome of cholecystectomies in patients with symptomatic cholelithiasis for improvement in the preoperative symptoms. MATERIALS AND METHODS: The study was conducted in a series of 60 cases of chronic calculus cholecystitis.Patients were selected from surgical outpatient Department of Darbhanga Medical College and Hospital. Laheriasarai. The tenure of study was from April 2019 to December 2020. Adetailed clinical history was taken from every patient to ascertain the diagnosis of chronic calculus cholecystitis. RESULTS AND ANALYSIS: The lump was localised in the right hypochondrium extending to the epigastrium or right lumbar region in some cases. The lump was tender and moves with respiration. Dowdy in 1969 described lump abdomen in 11.7% cases. The present ndings corroborated with that of the other research groups. CONCLUSION: Cholecystectomy appears to relieve most of the symptoms of gall stone disease. Biliary pain, nausea, vomiting and fatty food intolerance had better outcome compared to dyspepsia, atulence and heart burn. Some patients tend to develop de novo symptoms in the postoperative period. Despite the persistence or appearance of new symptoms, most of the patients feel satised with the outcome of surgery.