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 STUDY OF CLINICAL EFFECTIVENESS OF CHOLUDEXAN IN PATIENTS WITH CHRONIC ACALCULOUS CHOLECYSTITIS 
Professor G.G. Gurgenidze
Acad. O. Gudushauri National Medical Centre, Tbilisi, Georgia
Department of Internal Medicine.
 
According to the recent literature, chronic cholecystitis is one of the most common disorders of a gall bladder. Regarding statistical data from various authors approximately 23-27% of the world’s population suffer from it today (1,2). Usually the chronic inflammation of the gall bladder can be either result and/or complication of acute cholecystitis, although not infrequently it can develop in the absence of acute, painful attacks even in the presence of concrements. With this regard the clinical forms of acalculous cholecystitis are especially interesting to highlight, for which development of chronization of inflammatory process is the main factor. The chronic process of inflammation evolved in the presence of dyskinetic (mainly hypokinetic) gall bladder, pathologic chemical changes in the congested bile and secondary concommitant infections all lead to: increased lithogenicity, stratification of the gall bladder’s fluid media with micellium and formation of the crystallization centers between mucosa and submucosa [1, 4], which finally by itself lately can contribute to concrement formation. So chronic acalculous clinical forms of cholecystitis can be considered as the forerunners of cholestasis, even in early stages of the disease (according to some authors [4,5]). From the clinical point of view hyperkinetic forms of chronic cholecystitis are also significant, which in addition to described above are also mostly accompanied by development of duodenogastric reflux disease. The latter one by itself in the presence of chronicity causes reflux gastritis and not infrequently reflux esophagitis which even more worsens clinical picture and subjective feelings in the patients [3,6]. From everything described above, the rapid diagnosis and establishing of effective methods of treatments are crucialy important in preventive measures as well as in the treatment of accompanied gastrointestinal complications of the chronic acalculous cholecystitis.
 
Today, traditional conservative treatment of the chronic cholecystitis consists of specific nutrition modifications as well as of various groups of pharmaceutical medications. Especially analgetics, M-cholinolitics, selective and nonselective spasmolytics, antibacterial and antiprotozoal, also choleretic and cholekinetic medications are most widely used today. According to the pharmacologic mechanisms of action of the medications described above, it is obvious that the traditional treatment methods are directed to pain management, spasmolysis, antimicrobial action, and to bile flow modifications. Less attention is paid to correct such important factor as the unity of bile’s physico-chemical composition, because it is the disbalance in the bile’s composition that disregulates solubilization process of the firm particles and their crystallization, promote increase in bile density and so called biliary “sludge" formation. Accordingly it is quite logical that in the treatment of acalculous cholecystitis, medications successively affecting bile’s solubilization process (that increase its fluidity) should be extensively included.
 
This is why we have decided to conduct a study of clinical efficiency of the classic cholelitholytic substance – ursodeoxycholic acid ("Choludexan", “World Medicine", UK) in patients having chronic acalculous cholecystitis.
 
Material and methods. By using common clinical, ultrasonographic and endoscopic methods, 25 patients (15 women and 10 men) 36-53 years of age suffering from chronic acalculous cholecystitis were studied in the open controlled clinical trial. This so called treatment group was treated with Choludexan, while control group consisting of 15 patients (9 women and 6 men) 37-61 years of age were using only traditional conservative medications (Table No1).
 
In the population chosen by random selection, only those patients were included in trial who were diagnosed by medical history, clinical-laboratory data and instrumental methods of having mild to moderate and severe course of chronic acalculous cholecystitis [1,4]. For the assessment of severity of the clinical course special attention was payed to collection of medical history: namely, duration and sequence of disease exacerbation and remission phases; 6 month frequency history of ambulatorial or inhospital admissions. Detailed study was performed to explore remission phase stability and maintenance therapy course, indications for using: (M-cholinolytics, selective and nonselective spasmolytics, choleretics and cholekinetics during exacerbations), their dosages and clinical benefits.
 
Table No1. Demographic data of the studied (experimental) group.
 
Group
Data
Study Group
N=25
Control group
N =15
Men
10
6
Women
15
9
Age in years (M ± m)
42.7 ± 6.8
44.9 ± 7.4
Duration of the disease
(M ± m)
9.1 ± 3.6
11.2 ± 4.5
Disease course
Mild
9
6
Moderate
12
6
Severe
4
3
 
Study design: The study provided was open and unidirectional, duration of the studied group treatment was 60 days. Initially the patients were chosen according to detailed clinical history, complete blood count and urine analysis, abdominal ultrasonography, ECG and gastro-duodenoscopy with pH – metry. After this initial selection process, the chosen patients were treated with peroral Choludexan ("World Medicine",UK) for 60 days by 300mg once daily doses. Duration of treatment of the control group was also 60 days long, and the patients were treated by once a month Amoxicillin (10days long) regimen and also with procinetics and choleretics; no one was taking H2-blockers or antacids, besides usage of prokinetic and spasmolytic medications wasn’t prohibited.
 
For assessing the coarse of the disease specific daily questionaries were used, observing each symptom and complaint in detail. Special attention was payed to such complaints as were: pain in subscapular area (1), nausea (2), vomiting (3) and heartburn (4). The severity of each symptom was assesd via 0-3 score system scale (0=no symptom, 1=mild, 2=moderate, 3=severe). During the treatment period, assessing the general health status of the patients was performed by (-2 - +2) scoring system (-2=strong exaserbation,-1=mild exacerbation, 0=no change, +1=mild improvement, +2=marked improvement). Special attention was payed to the results of endoscopic studies wich were provided before and at the end of the clinical trial: pH metry for assessing intragastric acidity and detailed endoscopic analysis for discovery of the presence of bile reflux, changes in gastric mucosa and its spreading patterns. The probable side efffects of the medication was also monitored at the end of the each treatment course.
 
The Study Results.
From the 25 patients chosen for the experimental group only 24 individuals finished the study, one patient was dropped out from the study at the 3rd week of the trial because of noncompliance. Efficiency of the treatment plan was analysed only for those 24 patients who had finished the whole study regimen, but safity factors were studied for the whole 25 patients. During the observational period of the trial subjective scorring data collected from study and control group patients are provided in the tables 2 and 3.
According to these study results, Choludexan used according to the stated treatment protocol showed marked, statistically significant improvement in all of the four symptoms of the disease, including lessened pain and heartburn episodes. Assessmemt of the general health state of the patients also showed marked progress, during the treatment period statistically significant decrease in gastric acidity was also observed (pH increase from 2.8 to 3.5 units; 23.7% improvement); such results were not observed in the control group patients.
 
Table No 2. Symptoms of the patients in the experimental (study) group,
                         results of the sonographic and pH monitoring studies
Symptoms (N = 24)
Average score
(Before the treatment)
Average score
(After the treatment)
p value
Pain
2.11
0.67
< 0.01
Heartburn
2.42
0.85
< 0.01
Nausea
1.54
0.34
< 0.01
Vomiting
1.12
0.06
< 0.01
General state
----
1.87
---
pH units
2.8
3.5
< 0.05
Biliary sludge density( mm)
2.7
1.8
< 0.05
 
 
 
 
Table No 3. Symptoms of the patients in the control group,
                      results of the sonographic and pH monitoring studies
Symptom
(N = 15)
Average score
(Before the treatment)
Average score
(After the treatment)
p value
Pain
1.68
1.27
< 0.05
Heartburn
2.13
2.09
> 0.05
Nausea
1.22
1.31
>0.05
Vomiting
1.03
1.05
>0.01
General state
----
1.87
---
pH units
2.1
3.1
< 0.05
Billiary sludge density (mm).
2.9
2.4
< 0.05
 
During the treatment process in addition to marked clinical relief in patients from the study group, the results of the sonographic studies (billiary sludge density, kinetic parameters) also showed much better results. Such marked level of improvements wasn’t observed in the control group. And finally it must be stated that during the 8 week treatment course with Choludexan neither of it’s side effects were observed in the patients studied.
 
 
Summary
 
According to the results of the clinical trial we state that using of Choludexan’s 300mg daily doses during two months (stated by standard treatment protocol) for the treatment of chronic acalculous cholecystitis, is associated with significant clinical benefits. In addition Choludexan shows reduction in biliary sludge, normalizes gall bladder’s motoric functions, markedly reduces gastric acidity, and consequently lessens and ameliorates clinical symptoms and further complications of the reflux gastritis and reflux esophagitis.
 
Literature.
 
1. Маев И.В. "Холецистит: алгоритм диагностики и лечебной тактики", Москва, 2006, 64 стр.
2. Сулаберидзе Г., Гургенидзе Г. "Аутоиммунные нарушения при хроническом инфицировании желчного пузыря"; "Аллергология и иммунология", т.6, №4, 514-516, 2005.
3. Толпегина Т., Бурнашева Р. "Аллергия и заболевания желчного пузыря", Казань, 1988г., 110 стр.
4. Яковенко Е., Григорьев П. "Хронические заболевания внепеченочных желчевыводящих путей". Методические рекомендации, М.: Медицина, 2001.
5. "Gall bladder disorders" – A manual for practice. Dr. Falk Foundation, Freiburg, 2004.
6. "Cholesterol Gallstones and Ursofalk" Dr. Falk Foundation, Freiburg, 2005.