Approximately 3-15% of patients who have undergone removal of bile duct stones with endoscopic sphincterotomy have recurrence of stones which often presents as acute cholangitis. Despite better understanding on the factors and mechanisms underlying the recurrence of bile duct stones achieved during the past few decades, endoscopic removal still remains the mainstay of management for recurrent bile duct stones. Recently investigated and suggested management of recurrent bile duct stones are highlighted in this review.
Cholangiopancreatography, Endoscopic Retrograde ; Cholangitis/pathology ; Gallstones/surgery/*therapy ; Humans ; Recurrence ; Risk Factors ; Sphincterotomy, Endoscopic ; Ursodeoxycholic Acid/administration & dosage

Omega (omega)-3 polyunsaturated fatty acids appear to be effective in preventing and treating parenteral nutrition-associated liver disease, and several mechanisms were proposed for this observation. An 8-week-old male infant with cholestasis and acholic stool was diagnosed non-syndromic intrahepatic interlobular bile duct paucity by open-wedge liver biopsy. Initially he was treated with usual supportive medical therapy, including ursodeoxycholic acid. However, the clinical status and laboratory tests did not improve. Omega (omega)-3 polyunsaturated fatty acids (initially intravenous administration and oral administration later), were started and his liver function, including aminotransferase level and bilirubin levels normalized, and the ivory stool color turned green. We report the possible effectiveness of omega-3 polyunsaturated fatty acids as a potent choleretic agent for non-syndromic intrahepatic interlobular bile duct paucity, a very rare structural pediatric hepatic disease.
Administration, Intravenous ; Administration, Oral ; Bile Ducts* ; Bilirubin ; Biopsy ; Cholestasis* ; Fatty Acids, Omega-3 ; Fatty Acids, Unsaturated ; Humans ; Infant ; Liver ; Liver Diseases ; Male ; Ursodeoxycholic Acid

PURPOSE: The aims of this study are to measure the serum levels of fat soluble vitamins (vitamin A and D) from bile duct ligated rats, and to evaluate the effect of oral bile acids administration to facilitate absorption of fat soluble vitamins. METHOD: We measured serum ALT, total bilirubin, vitamin A, and vitamin D of Sprague-Dawley rats 1 week before and 4 weeks after experimental bile duct ligation. Rats were consisted with 3 groups. Group 2 had been find bile acids and group 3 ursodeoxycholic acid after operation for 4 weeks. Multi-vitamin was given to all groups. RESULTS: 1) Base line (mean value before duct ligation): ALT 74.2 IU, total bilirubin 0.26 mg/dL; vitamin D 13.01 ng/mL vitamin A 0.87 microgram/mL, total bile acids 25.16 micron mol/L. 2) Four weeks after ligation: ALT 100.7 IU, total bilirubin 2.58 mg/dL; vitamin D 7.89 ng/mL vitamin A 1.37 microgram/mL, total bile acids 278.22 micron mol/L. 3) 4 weeks after ligation, each group (group 1, group 2 and group 3) showed vitamin D (7.62, 8.10 and 7.99) ng/mL, vitamin A (1.68, 1.06 and 1.33) microgram/mL, total bile acids (233.17, 345.80 and 268.57) micron mol/L, which were statistically not significant. CONCLUSION: Serum level of vitamin A is increased after bile duct ligation although vitamin D is decreased. Oral administration of bile acids does not affect the serum levels of vitamin A and D in bile duct ligated rats.
Absorption ; Administration, Oral ; Animals ; Bile Acids and Salts ; Bile Ducts* ; Bile* ; Bilirubin ; Cholestasis ; Ligation ; Rats* ; Rats, Sprague-Dawley ; Ursodeoxycholic Acid ; Vitamin A ; Vitamin D ; Vitamins*

OBJECTIVETo observe the efficacy of ursodeoxycholic acid (UDCA) combined with glucocorticoids in the treatment of autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome.

METHODS19 patients with AIH-PBC overlap syndrome were divided randomly into two groups: initiate combined group and initiate UDCA-monotherapy group. Biochemical responses and pathological features before and after treatment were analyzed retrospectively with student's t test, Wilcoxon rank sum test and Fisher's exact method.

RESULTSIn the initiate combination group, biochemical responses in terms of AIH features (ALT decline to normal, IgG is less than or equal to 16 g/L) and PBC features (ALP decline ≥ 40% or to normal) were achieved. In UDCA-monotherapy group, no statistical difference existed in biochemical responses before adding glucocorticoids, whereas the levels of ALT, AST, GLB and IgG decreased significantly when combined with glucocorticoids. No statistical difference of rates of biochemical responses eixted between the two groups, whereas variance could be seen in different pathological stages. Alleviation of inflammatory infiltration after therapy appeared in 3 patients.

CONCLUSIONCombination therapy of UDCA with glucocorticoids could be suitable for AIH-PBC overlap syndrome. Early treatment is of benefit for achieving better biochemical response and pathological improvement.

Adult ; Alanine Transaminase ; analysis ; Drug Therapy, Combination ; Female ; Glucocorticoids ; administration & dosage ; therapeutic use ; Hepatitis, Autoimmune ; complications ; drug therapy ; Humans ; Immunoglobulin G ; analysis ; Liver Cirrhosis, Biliary ; complications ; drug therapy ; Male ; Middle Aged ; Treatment Outcome ; Ursodeoxycholic Acid ; administration & dosage ; therapeutic use

OBJECTIVETo conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) that have assessed the effect and safety of ursodeoxycholic acid (UDCA), S-adenosylmethionine (SAMe) and UDCA-SAMe combination therapies for intrahepatic cholestasis of pregnancy (ICP).

METHODSUsing searching protocols and assessment methods recommended by the Cochrane Collaboration to reduce bias in systematic reviews, the databases of Medline, EMBASE, Cochrane Central Register of Controlled Trials (CCRT), China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature (CBM) and Wanfang China Online Journals were searched to identify relevant RCTs published from database inception to December 2011.

RESULTSTen RCTs (of 727 pregnant women) were included in the study and represented a low risk for bias. Compared to the patients who received UDCA monotherapy, those who received UDCA-SAMe combination therapy had significantly lower rates of Cesarean section (odds ratio (OR) =0.45, 95% confidence interval (CI):0.24-0.86), preterm birth (OR=0.36, 95% CI:0.20-0.63), and fetal asphyxia (OR=0.27, 95% CI:0.13-0.56) (all P less than 0.05); however, the UDCA-SAMe therapy did not provide better rates of amniotic fluid pollution (OR=0.38, 95% CI:0.14-1.01) or better new bom weight (mean difference (MD) =397.36, 95% CI:-96.17-890.89). Compared to the patients who received SAMe monotherapy, those who received UDCA-SAMe combination therapy had significantly lower rates of preterm birth (OR=0.39, 95% CI:0.21-0.73), fetal asphyxia (OR=0.23, 95% CI:0.07-0.75), and amniotic fluid pollution (OR=0.41, 95% CI:0.20-0.85) (all, P less than 0.05); however, the UDCA-SAMe therapy did not provide better rates of Cesarean section (OR =0.62, 95% CI:0.27-1.44) or better new bom weight (MD =445.95, 95% CI:-143.51-1035.42). Comparison of the two monotherapies (UCDA vs.SAMe) showed no statistical differences in rates of Cesarean section (OR=0.91, 95% CI:0.47-1.78), preterm birth (OR =0.79, 95% CI:0.49-1.38), fetal asphyxia (OR=0.90, 95% CI:0.38-2.12), and amniotic fluid pollution (OR=1.14, 95% CI:0.61-2.13), as well as of new born weight (MD =-62.86, 95% CI:-157.81-32.09). Six studies reported no side effects.None of the included studies reported use of allocation concealment or blinding.

CONCLUSIONUDCA-SAMe combination therapy is better than either UDCA or SAMe monotherapy for improving the outcome of ICP without adverse effects. Large-scale trials with adequate sample sizes and higher quality study design are needed to further confirm the efficiency and safety of UDCA and SAMe for treating ICP.

Cholestasis, Intrahepatic ; drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Pregnancy ; Pregnancy Complications ; drug therapy ; Pregnancy Outcome ; Randomized Controlled Trials as Topic ; S-Adenosylmethionine ; administration & dosage ; adverse effects ; therapeutic use ; Ursodeoxycholic Acid ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUND/AIMS: Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms. METHODS: A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter < or =15 mm, GB ejection fraction > or =50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated. RESULTS: A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients. CONCLUSIONS: Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.
Adult ; Aged ; Antacids/*administration & dosage ; Chenodeoxycholic Acid/*administration & dosage ; Cholagogues and Choleretics/*administration & dosage ; Drug Administration Schedule ; Drug Combinations ; Female ; Gallstones/*drug therapy ; Humans ; Magnesium Hydroxide/*administration & dosage ; Male ; Middle Aged ; Prospective Studies ; Severity of Illness Index ; Solubility/drug effects ; Ursodeoxycholic Acid/*administration & dosage

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1beta (IL-1beta), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-1beta, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-1beta-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.
Administration, Oral ; Animals ; Cartilage* ; Cartilage, Articular ; Chondrocytes ; Extremities ; Humans ; Immunohistochemistry ; Injections, Intra-Articular ; Interleukin-1beta ; Interleukin-6 ; Joint Diseases ; Knee ; Knee Joint ; Liver Diseases ; Nitric Oxide Synthase Type II ; Nociception ; Osteoarthritis* ; Osteoclasts ; Oxidative Stress ; Rats* ; RNA, Messenger ; Ursodeoxycholic Acid*

To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial.
Administration, Oral ; Amyotrophic Lateral Sclerosis/*drug therapy ; Cholagogues and Choleretics/pharmacology/therapeutic use ; Cross-Over Studies ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Placebo Effect ; Severity of Illness Index ; Ursodeoxycholic Acid/pharmacology/*therapeutic use ; Vital Capacity/drug effects

BACKGROUND/AIMS: Chronic hepatocellular damage is closely associated with hepatic fibrosis and fatal complication in most liver diseases. The aim of this study is to compare the efficacy and safety of biphenyl dimethyl dicarboxylate (DDB) and ursodeoxycholic acid (UDCA) in patients with abnormal ALT. METHODS: One-hundred thirty-five patients with elevated ALT were randomized to receive either 750 mg/day of DDB or 300 mg/day of UDCA for 24 weeks in 4 referral hospitals. Ninety-three (69%) patients had non-alcoholic steatohepatitits, 27 (20%) had alcoholic hepatitis, and 15 (11%) had chronic hepatitis. The primary end point was the rate of ALT normalization at week 24. The secondary endpoints were changes in AST, liver stiffness, and the incidence of adverse events. RESULTS: A total of 101 patients completed 24 weeks of therapy. ALT normalization at week 24 was observed in 44 (80.0%) patients in DDB group and 16 (34.8%) in UDCA group (p<0.001). Higher mean reduction of ALT levels from baseline to 24 weeks was seen in DDB group compared with UDCA group (-70.0% vs. -35.9%, p<0.001). Normalization of AST level (p=0.53) and change in the liver stiffness (p=0.703) were not significantly different between the two groups. Severe adverse drug reaction occurred in 1 patient in DDB group but the subject continued therapy during the study period. CONCLUSIONS: DDB was not inferior to UDCA for normalizing ALT level. Furthermore it was safe and well tolerated by patients with abnormal ALT.
Adolescent ; Adult ; Aged ; Alanine Transaminase/*blood ; Cholagogues and Choleretics/*therapeutic use ; Dioxoles/*therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Hepatitis, Alcoholic/*drug therapy ; Hepatitis, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*drug therapy ; Tertiary Care Centers ; Treatment Outcome ; Ursodeoxycholic Acid/*therapeutic use ; Young Adult