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 ROLE OF CHOLUDEXAN IN THE TREATMENT OF LIVER DISORDERS 
Manana Makhviladze, Associated Professor,
Tbilisi State Medical University, Infectious Department
Depute General Director in medical part of
National Sepsis Centre named V. Bochorishvili
 
  
Ursodeoxycholic acid, main component of Choludexan, was isolated from the bile of bear, as expressed in its name. It represents the non-toxic tertiary bile acid. Ursodeoxycholic acid usage for destruction of cholesterol gallstones began in fifties of the last century. Clinical researches in subsequent years proved that therapeutic spectrum of Ursodeoxycholic acid is not confined only to this effect. According to U. Leuscher (1981) patients’ subjective conditions have been gradually improved, jaundice and pruritus decreased, biochemical measurements improved during the treatment process with Ursodeoxycholic acid (V. Mitsuyoshc H (1997)).
 
Bile acids are synthesized in hepatocytes, specifically in the smooth endoplasmic reticulum. Hepatocyte, as the main functional cell represents the universal "factory". The complex metabolic processes take place in it: bile formation and excretion, regulation of carbohydrate homeostasis, synthesis of plasma lipoproteins, cholesterol, steroids and main components of blood clotting factors. 250- 500 ml of bile acids are synthesized in liver and excreted in feces daily. Primary bile acids: cholic- and chenodesoxycholic acids are synthesized from cholesterol. They are conjugated with amino acids: glycine and taurine in the liver. Conjugation prevents their reabsorption in bile ducts and small intestine, but cannot prevent absorption in terminal portion of ileum. By the action of intestinal bacteria bile acids are dehydroxylated and secondary bile acids – desoxycholic and small quantity of lithocholic acids are formed. Tertiary bile acids, especially ursodeoxycholic acid, are formed in the liver, by isomerization of secondary bile acids. Absorbed bile acids reach liver by portal vein. Enterohepatic circulation of bile acids occurs 2-15 times a day.
 
Portion of ursodeoxycholic acid does not exceed 5 % of all bile acids, but in case of its regular usage blood concentration can be increased 10 times.   
 
Choludexan (Ursodeoxycholic acid) per oral usage decrease cholic and chenodesoxycholic acid absorption in small intestine. It is assumed that pruritus is caused by bile acid accumulation in the blood during jaundice. By inhibiting bile acid reabsorbtion Choludexan decreases this most inconvenient and irritable symptom of the patient. Ursodeoxycholic acid interacts with chenodeoxycholic acid and combined micelles are formed. They protect membranes of epithelic cells from damaging action of gastric contents in patients with billiary reflux-gastritis and reflux-esophagitis.
 
Choludexan interacts with liophilic structures of membranes, stabilizes them and protects from the action of cytotoxic micelles; protects patient’s liver from toxic effects of alcohol and of many hepatotoxic medication.
 
Important property of Choludexan is its ability to increase gallbladder motility and thus bile discharge and to decrease blood cholesterol level. It increases water, lecithin, cholesterol and bilirubin excretion in bile.  
 
Choludexan is a drug of choice in the treatment of cholelithiasis.  
 
Cholelithiasis is quite widespread disease. Its incidence increases with age. It is first manifested in 20-30 years of age and its prevalence is 20% of men and 30% of women in population of 65 years. Gallstones most commonly are composed of cholesterol. Normally bile is composed of cholesterol, bile acids and lecithin with 8%, 72% and 20 % respectively. Bile oversaturation with cholesterol, disturbance of enterohepatic circulation of bile acids, gallbladder functional disorders, and precipitation of cholesterol monohydrate crystals make billiary sediment (billiary sludge) and then stones. Besides ability to stimulate bile discharge and decrease bile cholesterol level, Chulodexan combines with cholesterol and phospholipids and makes solutions of micelles; it stimulates bile secretion and increase cholesterol precipitation time.
 
Researches made in last years describe immune-modulating action of Choludexan: Choludexan decreases antigen expression on membranes of hepatocytes and cholangiocytes with major histo-compatibility complex and stimulates synthesis of proinflammatory interleukine -2.  
 
There are some recommendations of Choludexan usage in the treatment of chronic hepatitis B and C in combination with interferon and nucleosides. According to randomized clinical trials there are also positive results of Choludexan treatment in patients with interferon resistance. 
And finally, it is important to carefully read instruction before usage of Choludexan.           
 
References:
 
1.      Мерк Шарп и Доум. Руководство по медицине. М. 1997.
2.      Соринсон С.Н. Вирусные гепатиты. С-П. 1998.
3.      Шерлок Ш., Дули Дж. Заболевания печени и жёлчных путей. М. 1999.
4.      Siegenthaler N, Kaufmann N, Hornbostel H, Waller N.D. Lehrbuch der Inneren Medizin. Stuttgart-New York. 1997.
5.      Kiso S., Kavata S., Tamura S. Efficacy of combination therapy in the treatment of interferon-a with ursodeoxycholic acid in chronic hepatitis C: A randomized controlled clinical trial. J. Gastroenterology, 1997 V 32 N1, p. 56-63.
6.      Ильченко А.А., Демокина О.В. Клиническое значение билиарного сладжа. Ж. Гастро-энтерология. Т. 7 /N2/ 2005.