U. Leuschner

Gallstone dissolution with ursodeoxycholic acid in patients with chronic active hepatitis and two years follow-up. A pilot study.

Chemical dissolution of cholesterol gallstones using ursodeoxycholic acid (UDCA) in six patients with histologically confirmed HBsAg-negative chronic active hepatitis was started after a minimum of one year of therapy with steroids, azathioprine, or chloroquine and a treatment-free period of 8–15 months. The treatment with UDCA lasted 3–20 months with a daily dose of 8–11 mg/kg. Four patients served as controls. A decrease in transaminases (P<0.05) occurred in all patients during the UDCA therapy. After completion of the treatment, the figures rose again, but did not return to the initial value. The stones dissolved in five patients. A second liver biopsy was carried out in two patients after UDCA therapy, and this showed no detectable deterioration. Four patients refused biopsy because the laboratory parameters had improved under UDCA. A stone recurred in one patient six months after the end of therapy; the others have remained free of stones for up to 24 months.

Gallstone dissolution with methyl tert-butyl ether in 120 patients--efficacy and safety.

Of 612 patients with cholesterol gallbladder stones, 120 were eligible for percutaneous transhepatic litholysis with methyltert-butyl ether (MTBE). Puncture of the gallbladder was successful in 117/120 (97.5%). In 113/117 (96.6%) the stones dissolved. With solitary stones, treatment lasted for an average of 4 hr, with multiple stones 10 hr. Mean hospitalization was 3.6 days. In 3/117 (2.6%) patients a bile leakage developed; 33% reported mild complaints. After the end of treatment 34% had some residue in the gallbladder; two of these patients developed recurrent stones. MTBE is exhaled, is distributed in fatty tissue, and is excreted renally together with its metabolitetert-butanol. Methanol was found only in traces. Gallbladder histology of six patients showed chronic cholecystitis. Since these findings were independent of treatment time and the interval between treatment end and operation, they are most consistent with stone-related changes rather than caused by MTBE.

Ursodeoxycholic Acid Therapy in Primary Biliary Cirrhosis

In a total of 1004 patients in 11 controlled trials, treatment with ursodeoxycholic acid (UDCA) 8-15 mg/kg bodyweight per day led to a decrease of pruritus in 30-60% of cases, a decrease in aminotransferases and cholestasis-indicating enzymes in serum by 20-80%, and a decrease of serum bilirubin by 3-40%. A statistically significant improvement in liver histology was found in only two of these studies; in three others there was a positive trend. In three more trials histology was not examined, and in three studies there was no improvement. In the four studies investigating the time elapsed before liver transplantation and the number of deaths, only one definitely found that this was prolonged by UDCA, although in two of the other three there was a positive trend. During treatment, UDCA constitutes 30-50% of the total bile acids in bile and serum; however, its influence on the toxic bile acids is debatable. Cholic acid decreases, but deoxycholic acid and chenodeoxycholic acid are reduced to a lesser degree. UDCA therapy has now been practiced for 12 years and all authors consider the treatment to be safe, but the mode of action of UDCA is still unknown.

Pigment Gallstone Dissolution in Vitro: Solubilization of Brown Bilirubinate and Black Polybilirubinate Stone Material by Buffered Solvents Containing Ethylenediaminetetraacetic Acid, Bile Salts, and Reducing Thiols

The efficacy of a buffered 1% ethylenediaminetetraacetic acid (EDTA)-2Na solution (pH 9.2) in solubilizing carefully pulverized material from brown bilirubinate and black polybilirubinate pigment stones can be intensified stepwise by admixtures of detergents and mucolytic active thiols. Solubilization effects were quantified either photometrically by measuring the dissolved calcium bilirubinate or gravimetrically by measuring the total weight loss of solids after a defined incubation period. Maximum effects were achieved when using a buffered solvent with 1 g/dl disodium-EDTA, 1 g/dl sodium taurocholate (NaTCA), and 2 g/dl N-acetylcysteine (NAC). Whereas admixtures of NAC enhanced the solubilization of brown bilirubinate stone material additionally by an average of 21.3% (related to the effect of an EDTA/NaTCA-containing solvent), black polybilirubinate material responded rather poorly and inconsistently to NAC (mean, 8.4 +/- 11.7%).

Cholic acid and ursodeoxycholic acid therapy in primary biliary cirrhosis

SummaryWe treated 6 patients with Stage II primary biliary cirrhosis with cholic acid (CA) 10 mg · kg−1 per day for 3 months and then with the same dose of ursodeoxycholic acid (UDCA). A matching group of 6 patients was observed for 3 months without any therapy. Liver function tests and serum and stool bile acids were investigated before, during and at the end of CA and UDCA therapy.The results of liver function tests deteriorated after 6–8 weeks of CA therapy and the changes were correlated (r=0.92) with an increase in α-dihydroxy-bile acids (chenodeoxycholic acid and deoxycholic acid) in the serum. The 24 h excretion of DCA in 24 h faeces was markedly increased.Ursodeoxycholic acid treatment improved liver function tests; after 4 weeks glutamate dehydrogenase (GLDH) had decreased. After 8–12 weeks of therapy ursodeoxycholic acid had increased to 50–60% of the total serum bile acids whereas the more apolar bile acids were significantly decreased. No changes in liver function tests or bile acid metabolism were found in the untreated group.Since CA and UDCA are non-toxic in man, this trial indicates that the apolar bile acids chenodeoxycholic acid and deoxycholic acid may be responsible for the deterioration of liver function in primary biliary cirrhosis. However, the therapeutic effect of UDCA cannot be explained merely by the decrease in α-dihydroxy-bile acids in the serum, since the laboratory results had improved prior to the decrease in the serum apolar bile acids.

Manual and automatic gallstone dissolution with methyl tert-butyl ether.

The aim of the study was to establish the efficiency of cholesterol gallstone dissolution with methyltert-butyl ether in a large group of patients and to compare the results of patients treated manually by a nurse or using an automatic pump. Gallbladder puncture was successful in 228 patients (99%). After 9 hr, 211 patients (91%) were stone-free; 144 (68%) of them left the hospital on the fourth day. In radiolucent stones not isodense with bile on a CT scan, dissolution rate decreased by 10%, treatment time was prolonged by 40%. Forty-two of the 228 patients were selected for the hand-syringed group, 42 patients, who matched these patients in stone size and number, were treated with an automatic pump (Baxter). Stone burden in matched pairs was comparable. Stones dissolved in 96% of the patients in both groups. Sludge remained in the gallbladder in 52% after manual treatment and 60% after automatic therapy. Side effects were identical in both groups. None of the side effects were pump-related. Automatic therapy reduced the time needed by the nurse to treat each patient by 70%.

Blind liver biopsy or guided biopsy ? A prospective study

SummaryBlind liver biopsy is sufficient for patients with diffuse-parenchymatous liver diseases. The accuracy rate of guided, laparoscopic liver biopsy is not enhanced.Laparoscopy is to be preferred to blind liver biopsy in focal disorders, since it provides with more information in patients with solitary carcinoma, cysts and other findings.The laparoscopist is being influenced by the knowledge of clinical data in making his diagnosis. The accuracy rate of laparoscopy is improved.The pathologist is but little or not at all influenced by clinical data.RésuméLa biopsie à l’aveugle est suffisante dans les altérations hépatiques parenchymateuses diffuses. La biopsie dirigée sous laparoscopie ne présente pas d’avantages.La laparoscopie est préférable à biopsie à l’aveugle dans les altérations focales et ne fournit pas d’informations supplémentaires chez les patients porteurs de lésions néoplasiques isolées, de kystes ou d’autres anomalies.Le laparoscopiste est influencé par la connaisssance des données cliniques et la précision de la laparoscopie s’en trouve majorée.Le pathologiste est peu ou pas influencé par les données cliniques.

Diurnal Rhythm of Bile Lipid Composition after Cholecystectomy and Papillotomy: Postpapillotomy Biliary Lithogenicity

The influence of the gallbladder and the sphincter of Oddi on the diurnal rhythm of bile lipid composition was assessed by determining the lithogenic index at 4-h intervals over a period of 24 h in 29 cholecystectomized and papillotomized patients with a nasobiliary tube receiving a normal hospital diet and in 9 during 1-day fast. With a normal diet, biliary cholesterol concentrations dropped during the daytime (p less than 0.05), and total biliary lipid, bile acid, phospholipid, and cholesterol concentrations rose at night (p less than 0.05). During fasting, total biliary lipid, phospholipid, and cholesterol concentrations rose continuously (p less than 0.01). Even with loss of function of the gallbladder and sphincter of Oddi, a diurnal rhythm of biliary lithogenicity persisted, caused mainly by cholesterol increases during fasting. Concomitant increases in phospholipids and, to a lesser extent, bile acids modulated these changes.

Clinical examination, laparoscopy and histology in the diagnosis of liver diseases : A prospective study in 900 patients

SummaryThe prospective study performed in 900 patients has shown that histological examination of liver tissue is most important in the diagnosis of diffuse-parenchymatous disorders. The accuracy rate reaches over 90%.On the other hand laparoscopy is superior to histological examination in focal-nodular disorders. In this group of diseases the inspection of the peritoneum and the abdominal cavity may contribute valuable informations.Based on clinical examinations only the definite diagnosis may be established in only approx. 30%.The positive evidence of such prospective studies is considerably influenced by the degree of severity of the disorders examined. In classical cases all correlations are excellent.RésuméL’étude prospective effectuée sur 900 patients montre l’importance de la biopsie hépatique dans les affections parenchymateuses diffuses avec un taux de précision supérieur à 90%.La laparoscopie est supérieure à l’histologie dans les lésions focales. Dans ce groupe, l’inspection du péritoine et de la cavité abdominale peuvent être contributives.Sur des bases uniquement cliniques le diagnostic définitif n’est obtenu que dans environ 30% des cas.Le degré de positivité des résultats de ce type d’étude prospective est très influencé par la sévérité des affections explorées. Dans les cas classiques, toutes les corrélations sont bonnes.

Medical Treatment of Cholesterol Gallstones: Present and Future

For 15 years it has been possible to dissolve cholesterol gallstones with chenodeoxycholic acid or ursodeoxycholic acid. There are now about 30 different chenodeoxycholic and ursodeoxycholic acid preparations available worldwide [10].