Gallstone disease - Drug treatment

Oral litholytic therapy is the only effective conservative method of treating cholelithiasis.

In patients with cholelithiasis, a decrease in the pool of bile acids is observed. This fact served as an incentive to study the possibility of dissolving gallstones using oral administration of bile acids, the results of which were successful. The mechanism of litholytic action is not an increase in the content of bile acids, but a decrease in the level of cholesterol in bile. Chenodeoxycholic acid inhibits intestinal absorption of cholesterol and its synthesis in the liver. Ursodeoxycholic acid also reduces the absorption of cholesterol and inhibits the normal compensatory activation of cholesterol biosynthesis. When treated with these drugs, the secretion of bile acids does not change significantly, but a decrease in cholesterol secretion leads to desaturation of bile. In addition, ursodeoxycholic acid increases the time of cholesterol precipitation.

Indications

Oral bile acid therapy is usually prescribed when patients are not candidates for surgery or do not agree to it. The patient must meet the eligibility criteria and be willing to undergo long-term (at least 2 years) treatment. Eligibility criteria include mild to moderate symptoms (no treatment is prescribed for “silent” stones), radiolucent stones, especially “floating” and small ones, up to 15 mm in diameter, preferably less than 5 mm, and a patent cystic duct.

Unfortunately, there are no imaging methods that can accurately determine the composition of the stones. In this regard, CT is more indicative than ultrasound, so given the high cost of bile acid treatment, its use is justified. Stones with an attenuation coefficient below 100 Hounsfield units (low calcium content) are more likely to dissolve.

Contraindications to the use of conservative therapy for cholelithiasis:

1. Complicated cholelithiasis, including acute and chronic cholecystitis, since the patient requires rapid sanitation of the bile ducts and cholecystectomy.
2. Disconnected gallbladder.
3. Frequent episodes of biliary colic.
4. Pregnancy.
5. Severe obesity.
6. Open ulcer of the stomach or duodenum.
7. Concomitant liver diseases - acute and chronic hepatitis, liver cirrhosis.
8. Chronic diarrhea.
9. Gallbladder carcinoma.
10. The presence of pigmented and calcified cholesterol stones in the gallbladder.
11. Stones with a diameter greater than 15 mm.
12. Multiple stones occupying more than 50% of the gallbladder lumen.

Chenodeoxycholic acid

In people who are not obese, chenodeoxycholic acid is used at a dose of 12-15 mg/kg per day. In severe obesity, an increase in cholesterol content in bile is observed, so the dose is increased to 18-20 mg/kg per day. The most effective is evening administration of the drug. Since a side effect of therapy is diarrhea, the dose is increased gradually, starting with 500 mg/day. Other side effects include a dose-dependent increase in AST activity, which usually decreases subsequently. Monitoring of AST activity is necessary by determining it monthly in the first 3 months and then 6, 12, 18 and 24 months after the start of treatment.

Ursodeoxycholic acid

It was isolated from the bile of the Japanese brown bear. It is a 7-p-epimer of chenodeoxycholic acid and is used in a dose of 8-10 mg/kg per day, increasing it in cases of severe obesity. The drug completely and more quickly than chenodeoxycholic acid dissolves about 20-30% of radiolucent stones. There are no side effects.

During treatment, the surface of the stones may become calcified, but this does not appear to affect its effectiveness.

Combination therapy

The combination of chenodeoxycholic and ursodeoxycholic acids, prescribed at 6-8 mg/kg per day, is more effective than ursodeoxycholic acid monotherapy and avoids the side effects associated with chenodeoxycholic acid monotherapy in higher doses.

Results

Oral bile acid therapy is effective in 40% of cases, and with careful selection of patients - in 60%. "Floating" stones up to 5 mm in diameter dissolve faster (complete disappearance in 80-90% of cases within 12 months), larger heavy ("sinking") stones require longer courses or do not dissolve at all. CT can determine the degree of calcification and avoid unindicated bile acid therapy.

Dissolution of gallstones can be confirmed by ultrasound or oral cholecystography. Ultrasound is a more sensitive method, allowing visualization of residual small fragments that are not visible during cholecystography. These fragments can serve as a nucleus for new stone formation.

The duration and severity of the effect of oral bile acid therapy vary. Relapses develop in 25-50% of patients (10% per year) with the highest probability in the first two years and the lowest probability in the fourth year after completion of the course of treatment in more distant periods.

A reduction in the recurrence rate of stones has been reported with prophylactic administration of ursodeoxycholic acid in low doses (200-300 mg/day). Recurrence is more frequent in patients with multiple stones before treatment.

The most favorable conditions for the outcome of oral lithotripsy are:

• in the early stages of the disease;
• in uncomplicated cases of cholelithiasis, rare episodes of biliary colic, moderate pain syndrome;
• in the presence of pure cholesterol stones (“float up” during oral cholecystography);
• in the presence of non-calcified stones in the bladder (CT attenuation coefficient less than 70 Hounsfield units);
• for stones no larger than 15 mm (in combination with shock wave lithotripsy - up to 30 mm), the best results are observed for stones up to 5 mm in diameter; for single stones occupying no more than 1/3 of the gallbladder; with preserved contractile function of the gallbladder.

Strict patient selection criteria make this method available to a very small group of patients with uncomplicated disease - approximately 15% with gallstone disease. High cost also limits the use of this method.

The duration of treatment ranges from 6 to 24 months with continuous administration of drugs. Regardless of the effectiveness of litholytic therapy, it reduces the severity of pain syndrome and reduces the likelihood of developing acute cholecystitis. Treatment is carried out under the control of the condition of the stones according to ultrasound data every 3-6 months. After the stones dissolve, the ultrasound is repeated after 1-3 months.

After the stones have dissolved, it is recommended to take ursodeoxycholic acid for 3 months at a dose of 250 mg/day.

The absence of positive dynamics according to ultrasound data after 6 months of taking the drugs indicates the ineffectiveness of non-oral litholytic therapy and indicates the need to discontinue it.

Antibacterial therapy. Indicated for acute cholecystitis and cholangitis.

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