Gallstone disease: drug treatment

Oral litholytic therapy is the only effective conservative treatment for cholelithiasis.

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

Indications

Oral therapy with bile acids is usually prescribed in cases where patients are not shown surgery or they do not agree to it. The patient must meet the selection criteria and be ready for a long (at least 2 years) treatment course. The selection criteria include mild or moderate symptoms (no treatment is prescribed for "mute" stones), X-ray negative stones, especially "floating" and small, with a diameter of up to 15 mm, preferably less than 5 mm, an open bladder duct.

Unfortunately, there are no visualization methods by which the composition of the stones could be accurately determined. In this respect, CT is more indicative than ultrasound, therefore, given the high cost of treatment with bile acids, its use justifies itself. More likely the dissolution of stones with an attenuation coefficient below 100 units. By Hounsfild (low in calcium).

Contraindications to the use of conservative therapy of cholelithiasis:

1. Complicated cholelithiasis, including acute and chronic cholecystitis, as the patient is shown a rapid sanation of the biliary tract and cholecystectomy.
2. Disconnected gallbladder.
3. Frequent episodes of biliary colic.
4. Pregnancy.
5. Pronounced obesity.
6. An open ulcer of the stomach or duodenum.
7. Concomitant liver diseases - acute and chronic hepatitis, cirrhosis.
8. Chronic diarrhea.
9. Carcinoma of the gallbladder.
10. The presence in the gallbladder of pigment and calcified cholesterol stones.
11. Stones with a diameter of more than 15 mm.
12. Multiple stones that occupy 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. With severe obesity, an increase in the cholesterol content in bile is observed, so the dose is increased to 18-20 mg / kg per day. The most effective evening reception of the drug. Since the side effect of therapy is diarrhea, the dose is increased gradually, starting at 500 mg / day. Other side effects include a dose-dependent increase in ACAT activity, which subsequently usually decreases. It is necessary to monitor ACAT activity by monthly detection in the first 3 months and then at 6, 12, 18 and 24 months after the start of treatment.

Ursodeoxycholic acid

It was isolated from the bile of a Japanese brown bear. It is a 7-p-epimer of chenodeoxycholic acid and is used at a dose of 8-10 mg / kg per day with an increase in it with pronounced obesity. The drug completely and faster than chenodeoxycholic acid dissolves about 20-30% of X-ray negative stones. There are no side effects.

During the treatment, the surface of the stones can be calcified, but this does not seem to affect its effectiveness.

Combination Therapy

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

results

Oral therapy with bile acids is effective in 40% of cases, and with careful selection of patients - in 60%. "Floating" stones with a diameter of up to 5 mm dissolve more quickly (complete disappearance in 80-90% of cases for 12 months), larger heavy ("sinking") stones require longer courses or do not dissolve at all. With the help of CT it is possible to determine the degree of calcification and avoid the not indicated therapy with bile acids.

Dissolution of gallstones can be confirmed with ultrasound or oral cholecystography. Ultrasound is a more sensitive method that allows visualization of residual small fragments that are not detected in cholecystography. These fragments can serve as the nucleus for the new formation of stones.

Duration and severity of the effect of oral therapy with bile acids vary. Relapses develop in 25-50% of patients (10% per year) with the greatest probability in the first two years and the smallest - in the fourth year after the end of the course of treatment at a more distant time.

There was reported a decrease in the frequency of recurrences of stone formation in the preventive administration of ursodeoxycholic acid in low doses (200-300 mg / day). In patients with multiple stones prior to treatment, relapses are more frequent.

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

• in the early stages of the disease;
• with uncomplicated course of cholelithiasis, rare episodes of biliary colic, mild pain syndrome;
• in the presence of pure cholesterol stones ("float" during oral cholecystography);
• if there are uncalcified stones in the bladder (weakening coefficient at CT is less than 70 units according to Hounsfield);
• when the size of the stones is not more than 15 mm (when combined with shock wave lithotripsy - up to 30 mm), the best results are noted with diameters of stones up to 5 mm; with single stones occupying not more than 1/3 of the gallbladder; with preserved contractile function of the gallbladder.

Rigid selection criteria for patients make this method available to a very small group of patients with uncomplicated course of the disease - approximately 15% with cholelithiasis. High cost also limits the use of this method.

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

After dissolution of stones, the use of ursodeoxycholic acid is recommended for 3 months at a dose of 250 mg / day.

The lack of positive dynamics according to ultrasound after 6 months of taking medications indicates the ineffectiveness of non -oral litholytic therapy and indicates the need for its cessation.

Antibacterial therapy. It is indicated for acute cholecystitis and cholangitis.

[1], [2], [3], [4], [5], [6], [7]