Evaluation of therapeutic effect of oral Ursodeoxycholic Acid on indirect hyperbilirubinemia in term neonates undergoing phototherapy: A randomized controlled clinical trial.

INTRODUCTION AND AIMS: Phototherapy is the most common treatment modality of neonatal hyperbilirubinemia. We aimed to evaluate the therapeutic effect of oral Ursodeoxycholic Acid (UDCA) on indirect hyperbilirubinemia in term neonates undergoing phototherapy. MATERIALS AND METHODS: This randomized controlled clinical trial was performed on 106 full-term neonates with jaundice who were admitted to the neonatal ward of 17 Shahrivar Hospital in Rasht, Iran. The neonates were randomly assigned to two groups of intervention (10 mg/kg UDCA+phototherapy) and control (phototherapy alone). Total serum bilirubin (TSB) was measured at the time of admission, during first 12, 24, and 48 hours after admission and at the time of discharge. The duration of hospitalization and side effects were also assessed in both groups. IBM SPSS Statistics for Windows, version 20 was used to analyze the data. RESULTS: Results showed that in the intervention group, 28 (52.8%) of neonates were boys with the mean age of 5.1±1.25 days. While, in the control group 29 (54.7%) of them were boys with the mean age of 5.19±2.26 days. Bilirubin levels in both groups decreased significantly after hospitalization (at 12, 24 and 48 hours) (P <0.001). The mean of bilirubin at 12, 24 and 48 hours in the intervention and control groups were 17.1, 13.2, 10.2 mg / dl and 17.1, 14.2 and 11.3 mg / dl, respectively. At the time of discharge, TSB in the former compared to the latter group was significantly reduced (7.74± 1.39 vs. 8.67±1.35) (P = 0.001). In addition, the duration of hospitalization was considerably shorter in the intervention compared to the control group (P = 0.038) and no side effects were observed. CONCLUSIONS: Administering UDCA plus phototherapy reduced TSB and length of hospital stay with proper safety and efficacy. Therefore, it seems that this combination can be an appropriate treatment modality in neonatal hyperbilirubinemia.

[Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond].

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond / 中国中药杂志

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Effect of S-adenosyl-L-methionine on liver biochemistry and quality of life in patients with primary biliary cholangitis treated with ursodeoxycholic acid. A prospective, open label pilot study.

BACKGROUND AND AIMS: Chronic liver disease induces an acquired deficiency of S-adenosyl-L-methionine (SAMe) leading to impairment of detoxifying processes in the liver. Ursodeoxycholic acid (UDCA) represents the standard treatment in primary biliary cholangitis (PBC). As both compounds exert their hepatoprotective effects by different mechanisms, it is conceivable that when used together their effect might be additive. The aim of this study was to analyse the effect of SAMe supplementation on liver biochemistry and health-related quality of life (HRQoL) in patients with PBC, treated with UDCA. METHODS: In this prospective pilot, proof of the principle, non-randomized and open label study we enrolled 24 patients with PBC treated with UDCA for at least 6 months. They had received both UDCA in a standard dose of 13-15 mg/kg b.w. and SAMe in the dose of 1200 mg daily over a period of 6 months. A group of 24 patients with PBC treated with UDCA served as control for liver biochemistry (Study registered on the platform ClinicalTrials.gov under ID: NCT02557360). RESULTS: We observed a significant decrease of ALP, GGT and total cholesterol in non-cirrhotic patients treated with SAMe. There was also a significant improvement of fatigue and pruritus in PBC-40 questionnaire and amelioration of anxiety in STAI 2 questionnaire in the SAMe group. Treatment with SAMe neither increased sulfation capacity of the liver nor had an effect on fibroblast growth factor-19 serum levels. CONCLUSIONS: Our pilot study demonstrates a positive effect of adding SAMe to UDCA in non-cirrhotic patients with PBC.

Long-Term Ursodeoxycholic Acid Therapy Does Not Alter Lithocholic Acid Levels in Patients with Cystic Fibrosis with Associated Liver Disease.

OBJECTIVE: To evaluate the fasting and postprandial serum bile acid composition in patients with cystic fibrosis-associated liver disease (CFLD) after chronic administration of ursodeoxycholic acid (UDCA) (20 mg/kg/day). The aim was to specifically focus on the extent of biotransformation of UDCA to its hepatotoxic metabolite, lithocholic acid, because of recent concerns regarding the safety of long-term, high-dose UDCA treatment for CFLD. STUDY DESIGN: Twenty patients with CFLD (median age 16 years, range: 2.4-35.0) prescribed UDCA therapy for at least 2 years were studied. Total and individual serum bile acids were measured by stable-isotope dilution mass spectrometry, in fasting and 2-hour postprandial samples taken during chronic UDCA (20 mg/kg/day) administration. RESULTS: During chronic UDCA administration (median duration 8 years, IQR: 6-16), UDCA became the predominant serum bile acid in all patients (median, IQR: 3.17, 1.25-5.56 µmol/L) and chenodeoxycholic acid concentrations were greater than cholic acid (1.86, 1.00-4.70 µmol/L vs 0.40, 0.24-2.71 µmol/L). The secondary bile acids, deoxycholate and lithocholate, were present in very low concentrations in fasted serum (<0.05 µmol/L). After UDCA administration, 2-hour postprandial concentrations of both UDCA and chenodeoxycholic acid significantly increased (P < .01), but no significant changes in serum lithocholic acid concentrations were observed. CONCLUSION: These data do not support recent suggestions that enhanced biotransformation of UDCA to the hepatotoxic secondary bile acid lithocholic occurs when patients with CFLD are treated with relatively high doses of UDCA.

Efficacy and Safety of "URSA Complex" in Subjects with Physical Fatigue: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Fatigue is a common symptom both in diseases status and in healthy subjects. Various supplements and nutraceuticals for relieving of fatigue have been used. However, there are a few studies to evaluate the efficacy and the safety of the drug for fatigue alleviation, we conducted using URSA Complex to evaluate the efficacy on physical fatigue via score changes in the checklist individual strength (CIS). METHODS: The study was designed as a multicenter, randomized, double-blind, placebo-controlled trial, with subjects randomized to one of the two arms, receiving either placebo or URSA Complex administered as identical capsules. The primary efficacy endpoints of this clinical trials are the ratio of improving CIS scores < 76 points in patients at the end (4 weeks). Secondary efficacy variables are as follows one is an improvement of fatigue and the other is an improvement of the liver enzyme. RESULTS: The fatigue recovery rate in who had improved CIS scores of < 76 points were 70.0%, 50.9% in the therapy group and placebo group, respectively (P = 0.019). The fatigue recovery rate in CIS score was higher in URSA Complex therapy group than placebo group. The difference between therapy group and placebo group was statistically significant at 4 weeks later, but not 2 weeks. CONCLUSIONS: Our results provided that the URSA Complex was effective in alleviating physical fatigue. The adverse event frequency in the therapy groups was similar to that in the placebo group.

High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis.

BACKGROUND: Ursodeoxycholic acid (UDCA) in a dose of 28-30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. AIM: To compare the risk of adverse clinical endpoints in patients with varying disease status. METHODS: We reviewed records from patients previously enrolled in a study evaluating the effects of high dose (28-30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histological stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, oesophageal varices and cholangiocarcinoma was sought. RESULTS: A total of 150 patients were included of whom 49 patients developed endpoints. There was an increased development of endpoints among patients using UDCA vs. placebo (14 vs. 4, P=0.0151) with early histological disease (stage 1-2, n=88) but not with late stage (stage 3-4, n=62) disease (17 vs. 14, P=0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, P=0.0008) with normal bilirubin levels (total bilirubin ≤1.0 mg/dL) but not in patients with elevated bilirubin levels (15 vs. 16, P=0.6018). Among patients not reaching endpoints 31.7% had normalisation of their alkaline phosphatase levels when compared to 14.3% in patients who reached endpoints (P=0.073). CONCLUSION: The increased risk of adverse events with UDCA treatment when compared with placebo is only apparent in patients with early histological stage disease or normal total bilirubin.

High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis.

UNLABELLED: Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long-term, randomized, double-blind controlled trial of high-dose UDCA (28-30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n = 76) and placebo (n = 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]). CONCLUSION: Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events.

Ursodeoxycholic acid treatment in preterm infants: a pilot study for the prevention of cholestasis associated with total parenteral nutrition.

In a prospective, double-blind, placebo-controlled trial, the efficacy and safety of ursodeoxycholic acid (UDCA) was evaluated in preterm infants, in terms of its potential impact on fat absorption, advancement of enteral feeding, development of cholestasis, growth, nutritional status, and metabolic status. Although fecal fat excretion slightly decreased and achievement of full enteral feeding was earlier in the UDCA group, these differences were not significant. Interestingly, whereas serum gamma-glutamyl transferase activity increased during the parenteral nutrition period in the placebo group, we observed a constant and significant decrease in the UDCA group. This observation warrants further investigation to determine the utility of prophylactic UDCA in preventing cholestasis in infants with prolonged parenteral nutrition.

Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment.

BACKGROUND/AIMS: Despite a proposed role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis, antioxidant approaches have not been investigated sufficiently in the therapy of nonalcoholic steatohepatitis. Our aim was to determine whether vitamin E plus C therapy is effective in normalization of liver enzymes compared to ursodeoxycholic acid treatment in patients with fatty liver disease. METHODS: This was an open-labeled, prospective, randomized study enrolling patients with histologically proven fatty liver disease who had chronically elevated alanine aminotransferase, despite a three-month reducing diet. Patients consuming alcohol (more than 20 g/day) were excluded. The patients were randomly prescribed either oral vitamin E (600 IU/day) plus vitamin C (500 mg/day) or ursodeoxycholic acid (10 mg/kg/day). Patients were randomized as two groups to receive vitamin E plus vitamin C combination (28 patients, 10 F) or ursodeoxycholic acid treatment (29 patients, 13 F). RESULTS: There was no significant change in body mass index before and after the treatment in both groups. At the end of six months of therapy, serum aspartate aminotransferase and aminotransferase levels significantly decreased in both treatment options. Vitamin E and C combination was more efficacious on serum aminotransferase levels than ursodeoxycholic acid, but the difference was not significant. Alanine aminotransferase decreased to normal levels in 17 of 27 (63%) and in 16 of 29 patients (55%), respectively, in the two groups. Gamma-glutamyl transpeptidase decreased in patients receiving ursodeoxycholic acid, but no change was obtained in the vitamin-treated patients. CONCLUSIONS: Vitamin E plus C combination treatment is a safe, inexpensive and effective treatment option in patients with fatty liver disease, with results comparable to those obtained with ursodeoxycholic acid. Since more effective new therapeutic options are lacking, patients with fatty liver disease should be encouraged to take vitamin E and C supplements, which are safe and affordable.

[Menthol in the adjuvant treatment of gallbladder stones fragmented by ESWL as an option for reducing doses of urso- and chenodeoxycholic acid]. / Mentholsubstitution als Option zur Dosisreduktion von Urso- und Chenodeoxycholsäure in der adjuvanten Therapie nach ESWL von Gallenblasensteinen.

BACKGROUND: Assessments of the litholytic activity of terpenes in the conservative treatment of gallstone disease vary. Achievement of a stone-free state through dissolution of residual fragments after extracorporeal shock wave lithotripsy (ESWL) is a suitable model for investigating the litholytic activity of menthol. PATIENTS AND METHODS: After ESWL in patients with symptomatic gallbladder stones, the litholytic efficacy of the standard therapy of 125 mg urso-/chenodeoxycholic acid (UDC/CDC) per 25 kg body weight (UDC + CDC) was compared with that of 62.5 mg UDC/CDC plus 125 mg menthol (M) per 25 kg body weight (M + UDC + CDC). 70 patients were treated with M + UDC + CDC (n = 36) or UDC + CDC (n = 34) in a double-blind design. RESULTS: 19 of 34 patients (55.9%) in the UDC + CDC group became stonefree in an average period of 5.9 months, compared with 17 out of 36 patients (47.2%) in the M + UDC + CDC group in 8.8 months. Although the patients on UDC + CDC became stone-free significantly more quickly (p = max [p1,p2] = 0.4717), there was no relevant statistical difference in the total number of stone-free patients between the two treatment groups. After subtraction of the patients who terminated the study prematurely, significantly larger numbers of stone-free patients under the standard therapy were found at 9 and 12 months (16 : 9 and 19 : 12, respectively), while at the other time points no significant difference was found. Before ESWL, seven of 25 patients in the menthol group had two or more stones, while in the group treated with the standard therapy this was only the case in two patients. Five patients had mild calcification on admission to the study, four of whom received M + UDC + CDC. CONCLUSION: Overall, patients become stone-free more quickly on the standard UDC + CDC therapy. However, after subtraction of the patients who discontinued the study prematurely it can be seen that this results from significantly higher numbers of stone-free patients at 9 and 12 months, so that over the entire observation period-and in consideration of the less favorable stone parameters in the menthol group-there is no substantial statistically relevant difference in the efficacy of the two treatments.

[Clinical features of primary biliary cirrhosis and treatment of it by integrated traditional Chinese and western medicine].

OBJECTIVE: To investigate the clinical features of primary biliary cirrhosis (PBC) and its treatment by integrated traditional Chinese and western medicine. METHODS: 16 PBC patients were observed. Ursodeoxycholic acid (UDCA) was used in the dose of 13 to 15 mg.kg(-1).d(-1), with some traditional Chinese herb prescription. Results (1) The proportion of women to men was 15:1, the mean age was 52.5 years. AMA-M2 was positive in 14 subjects (87.5%). Biliary tract enzymes and ESR were elevated in all subjects. The ratio of hypercholesterolemia (CHOL) and abnormality in IgM was high (62.5%). Fatigue, pruritus, arthralgia, jaundice, splenomegaly were noted in more than half cases. Every patient had one to four complications. (2) ALP, GGT and Glb declined evidently after 3 months' treatment by western medicine associated with traditional Chinese medicine, and declined markedly after 12 months' treatment (P<0.05 respectively). TBIL and CHOL declined gradually during the treatment course. Symptoms and signs were lightened. CONCLUSION: PBC has complicated and especial clinical features. UDCA therapy is effective in PBC, while traditional Chinese medicine has extraordinary effect in treating the symptoms and signs.

Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a randomized trial.

BACKGROUND/AIM: Ursodeoxycholic acid in doses of 13-15 mg x kg(-1) x day(-1), is a safe and cost-effective treatment for patients with primary biliary cirrhosis. However, very limited information exists regarding the most appropriate dose of ursodeoxycholic acid. The aim of the study was to compare three dosages of ursodeoxycholic acid with respect to changes in liver biochemistries, Mayo risk score, biliary enrichment with ursodeoxycholic acid and side effects over at least a 1-year period. METHODS: A total of 155 patients were randomized to receive low- (5-7 mg x kg(-1) x day(-1)), standard-(13-15 mg x kg(-1) x day(-1)), and high- (23-25 mg x kg(-1) x day(-1)) doses of ursodeoxycholic acid. RESULTS: The improvements in alkaline phosphatase (p = 0.0001), aspartate aminotransferase (p = 0.0001), Mayo risk score (p = 0.002), and ursodeoxycholic acid enrichment (p = 0.0001) were significantly greater in the standard- and high-dose groups compared to the low-dose group, but not between the standard- and high-dose groups. Changes in serum bilirubin were similar between the three groups (p = 0.07). No significant effects on symptoms were noted with any dose. No patients discontinued ursodeoxycholic acid because of side effects or toxicity. CONCLUSIONS: Ursodeoxycholic acid in doses of 5-25 mg x kg(-1) x day(-1) is safe and well tolerated. The dose of 13-15 mg x kg(-1) x day(-1) appears to be the preferred dose for patients with primary biliary cirrhosis.

Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis.

Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis (CF). Preliminary data suggest that ursodeoxycholic acid (UDCA) may be beneficial for treatment of this manifestation. We performed a double-blind, multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA. From June to December 1990, we enrolled in 12 centers 55 CF patients with liver disease (39 male subjects; median age, 13.8 years). They were randomly assigned to receive for 1 year one of the following treatments: UDCA (15 mg/kg body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or double placebo. Clinical and laboratory evaluations were performed every 3 months. After 1 year, deterioration of overall clinical conditions, as indicated by the Shwachman-Kulczycki score (SKS), occurred in patients who received placebo but not in those who received UDCA (P = .025). Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase (GGT) (P = .004) and 5'-nucleotidase (P = .006) levels. Treatment with taurine was followed by a significant increase in serum prealbumin levels (P = .053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical profile. No severe side effects occurred with any treatment. Thus, we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease. Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status.

Is ursodeoxycholic acid an effective therapy for total parenteral nutrition-related liver disease?

Cholestasis is the predominant complication in patients with total parenteral nutrition-related liver disease. Ursodeoxycholic acid has been reported to be beneficial for patients with various chronic cholestatic liver diseases. The aim of this prospective study was to determine the effects of short-term administration of ursodeoxycholic acid in nine patients (mean age 54 years) treated with home total parenteral nutrition (31 +/- 2 (mean +/- SEM) kcal/kg per day) for 13.9 +/- 5.2 months for short bowel syndrome; all presented biological evidence of hepatic cholestasis (mean alkaline phosphatase activity 5.2 times the upper limit of the normal) which appeared during nutrition; there was no cause of hepatic dysfunction other than total parenteral nutrition. Patients received 11.2 +/- 0.8 mg/kg per day of ursodeoxycholic acid orally for 1 (n = 9) or 2 (n = 5) 2-month periods, each of which was followed by a 2-month wash-out period. Liver function tests were performed before and at the end of each period. Compared with non-treatment periods, the two periods of ursodeoxycholic acid administration induced a significant reduction in gamma-glutamyl transpeptidase (27.1% and 20.4% respectively; p = 0.001) and alanine aminotransferase serum activities (7.0% and 34.8% respectively; p = 0.01) from baseline values. Alkaline phosphatase activity (p = 0.09), aspartate aminotransferase (p = 0.11) and bilirubin (p = 0.75) serum activities underwent no significant change during the study. These preliminary results strongly suggest that short-term ursodeoxycholic acid administration leads to biochemical improvement in liver function tests in patients with total parenteral nutrition-related liver disease.

Oral bile acid treatment of biliary cholesterol stones.

Cholesterol gallbladder stones can be dissolved with chenodeoxycholic acid (CDCA) or ursodeoxycholic acid (UDCA). Response rate is 60-90%, dissolution rate 60% in stones not exceeding 1.5 cm in diameter. Mean treatment time amounts to 18 months. To improve oral litholysis: 1) UDCA was combined with the amino acid taurine, 2) CDCA and UDCA were administered in a single bedtime dose, 3) they were combined, each bile acid in half dosage, and 4) they were mixed with terpenes. Although there was some improvement with the combination therapy, final outcome is still suboptimal. Many investigations have been performed concerning gallbladder function, mucus production and nucleating factors, showing both that cholesterol supersaturation of bile is the conditio sine qua non for gallstone formation and that other factors play an additional, important role for the development of the first nidus. These factors have to be considered when therapy shall be improved. As yet oral litholysis has shown neither drug-related side effects nor lethality. It is not more expensive than surgery. Direct contact litholysis with methyl tert-butyl ether could reduce the indication for oral treatment to floating stones or patients who refuse gallbladder puncture. But although oral litholysis does not provide us with optimal results and needs further improvements, it will always keep its place in gallstone therapy.

Cytoprotection in the nineties: experience with ursodeoxycholic acid and silymarin in chronic liver disease.

The authors report their experience in the use of ursodeoxycholic acid and silymarin in patients with active cirrhosis of different aetiology. Both drugs seemed safe and ameliorated the biochemical indices of cytolysis; however, the former did not appear to be effective when hepatic dysfunction was associated to hepatitis C infection. The residual functional liver mass, as assessed by quantitative liver function tests, was not affected by either cytoprotective agent.

Efficacy and safety of a combination of chenodeoxycholic acid and ursodeoxycholic acid for gallstone dissolution: a comparison with ursodeoxycholic acid alone.

Chenodeoxycholic acid (CDC) and ursodeoxycholic acid (UDC) have distinct physicochemical and metabolic properties which, being complementary, should favor more rapid removal of cholesterol from gallstones when both bile acids are administered together. To see if the combination is more effective and well tolerated, we have compared 5 mg/kg of CDC plus 5 mg/kg of UDC with a 10-mg/kg dose of UDC alone in 120 patients with radiolucent, sonographically confirmed gallstones and characteristics favoring complete dissolution. Ursodeoxycholic acid was chosen as the reference because it dissolves stones faster and is better tolerated than CDC. To minimize the influence of stone size, the major determinant of dissolution, patients were divided, on admission, into two groups according to the maximum stone diameter: 50 had stones less than or equal to 5 mm, 70 had stones greater than 5 mm but less than 15 mm. The effects of treatment on stone dissolution evaluated by cholecystography and ultrasonography at 6, 12, and 24 mo, were analyzed by the actuarial life-table method. In the group with smaller stones, significantly more patients had obtained complete dissolution after treatment with the combination (52%) than after treatment with UDC alone (24%) at 6 mo. After longer periods, results were still better with the combination, although the differences from UDC alone became smaller. In the patients with larger stones, rates of complete and partial dissolutions were higher after treatment with the combination (51% vs. 24% with UDC) at 6 mo and again the differences had become smaller after longer treatment. Although not statistically significant, stone calcification occurred more often with UDC (7 cases) than with the combination (1 case). We conclude that CDC plus UDC is preferable to UDC alone because it dissolves stones more quickly, with a lower incidence of stone calcification, and may result in reduced cost of treatment.