Risk factors for recurrence of common bile duct stones after surgical treatment and effect of ursodeoxycholic acid intervention

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an accurate diagnostic method for choledocholithiasis and treatment option for stone removal.Additionally,ursodeoxycholic acid(UDCA)can dissolve cholesterol stones and prevent their development and reappearance by lowering the cholesterol concen-tration in bile.Despite these treatment options,there are still patients who experience stone recurrence.The clinical data of 100 patients with choledochal stones who were hospitalized at the Yixing People’s Hospital and underwent ERCP for successful stone extraction between June 2020 and December 2022 were retrospectively collected.According to the post-ERCP treatment plan,100 patients were classified into UDCA(n=47)and control(n=53)groups.We aimed to assess the clinical efficacy and rate of relapse in the two patient populations.We then collected information(basic demographic data,clinical characteristics,and serum biochemical indicators)and determined the factors contributing to relapse using logistic regression analysis.Our secondary goal was to determine the effects of UDCA on liver function after ERCP.Compared to the control group,the UDCA group demonstrated a higher clinical effectiveness rate of 92.45%vs 78.72%(P<0.05).No significant differences were observed in liver function indices,including total bilirubin,direct bilirubin,gamma-glutamyl transpeptidase,alanine aminotransferase,alkaline phosphatase,and aspartate aminotransferase,between the two groups before treatment.After treatment,all liver function indices were significantly reduced.Comparing the control vs UDCA groups,the UDCA group exhibited significantly lower levels of all indices(55.39±6.53 vs 77.31±8.52,32.10±4.62 vs 45.39±5.69,142.32±14.21 vs 189.63±16.87,112.52±14.25 vs 149.36±15.36,122.61±16.00 vs 171.33±22.09,96.98±10.44 vs 121.35±11.57,respectively,all P<0.05).The stone recurrence rate was lower in the UDCA group(13.21%)in contrast with the control group(44.68%).Periampullary diverticula(OR:6.00,95%CI:1.69-21.30),maximum stone diameter(OR:1.69,95%CI:1.01-2.85),stone quantity>3(OR:4.23,95%CI:1.17-15.26),and positive bile culture(OR:7.61,95%CI:2.07-27.91)were independent factors that influenced the relapse of common bile duct stones after ERCP(P<0.05).Furthermore,postoperative UDCA was identified as a preventive factor(OR:0.07;95%CI:0.08-0.09).CONCLUSION The intervention effect of UDCA after ERCP for common bile duct stones is adequate,providing new research directions and references for the prevention and treatment of stone recurrence.

Effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine on pregnancy outcomes in intrahepatic cholestasis

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes.The condition is typically marked by pruritus(itching)and elevated levels of liver enzymes and bile acids.The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate,but the efficacy of this approach remains less than optimal.Recently,polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects.AIM To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate on bile acid levels,liver enzyme indices,and pregnancy outcomes in patients with ICP.METHODS From June 2020 to June 2021,600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via randomnumber table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(control group,n=300)or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(combined group,n=300).Outcome measures included bile acids levels,liver enzyme indices,and pregnancy outcomes.RESULTS Prior to treatment,no significant differences were observed between the two groups(P>0.05).Post-treatment,patients in both groups had significantly lower pruritus scores,but the triple-drug combination group had lower scores than the dual-drug combination group(P<0.05).The bile acid levels decreased significantly in both groups,but the decrease was more significant in the triple-drug group(P<0.05).The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group(P<0.05).CONCLUSION Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP,providing a positive impact on pregnancy outcome and a high safety profile.Further clinical trials are required prior to clinical application.

Impact of Ursodeoxycholic Acid on Gall Stone Formation Post Bariatric Surgery

Introduction: Bariatric surgery is identified as highly effective therapy for obesity and help to loss wight that is become important public health priority because it increases the risk of condition including diabetes, cardiovascular disease, and several types of cancer whether by accomplishing mini-gastric bypass, Gastric bypass (Roux-en-Y) and sleeve gastrectomy [1] rapid weight loss increased incidence risk of gall stone formation [2]. Ursodeoxycholic acid is a bile acid which affect a reduction in cholesterol in biliary fluid primary by dispersing the cholesterol and forming a liquid-crystal phase [2], it’s can play a significant role in preventing of gall stone formation. Objective: Study potential effect of Ursodeoxycholic acid (UDCA) on gall stone formation after bariatric surgery. Methods: This study Cross-sectional Trials, review of all patient underwent bariatric surgery November 2021-Jun 2022, Taif Military Hospital in the department of surgery, the sample of study will be around 143 participants or more, data collection all patient underwent bariatric surgery. Results: A Total of 160 patients underwent bariatric surgery in Taif Armed Forces Hospitals from 2015 to 2021. Of these, 53 were male (33.1%) and 107 were female (66.9%). only 33 patients (20.6%) received Ursodeoxycholic acid, and 127 patients (79.4%) weren’t proscribed for them. However, 40 patients (25%) develop gall stone and underwent cholecystectomy, three of them were on Ursodeoxycholic acid (9%) and 37 patients weren’t on Ursodeoxycholic acid (29%). which shows that Ursodeoxycholic acid remarkable reduce the risk of gall stone formation post wight reduction surgery. Conclusion: In conclusion, bariatric procedures come with the risk of leading to the formation of gallstones. This is especially in the stage when a patient experiences rapid loss of weight. This is why a preventive measure is necessary and UDCA have been considered for this purpose. This study has shown that patients who use UDCA are less bound to have gallstone formations.

Efficacy and Safety of Tauroursodeoxycholic Acid in the Treatment of Liver Cirrhosis: A Double-blind Randomized Controlled Trial

No direct comparison of tauroursodeoxycholic acid （TUDCA） and ursodeoxycholic acid （UDCA） has yet been carried out in the treatment of liver cirrhosis in China. We designed a double-blind randomized trial to evaluate the potential therapeutic efficacy of TUDCA in liver cirrhosis, using UDCA as parallel control. The enrolled 23 patients with liver cirrhosis were randomly divided into TUDCA group （n=12） and UDCA group （n=l 1）, and given TUDCA and UDCA respectively at the daily dose of 750 mg, in a randomly assigned sequence for a 6-month period. Clinical, biochemical and histological features, and liver ultrasonographic findings were evaluated before and after the study. Ac- cording to the inclusion criteria, 18 patients were included in the final analysis, including 9 cases in both two groups. Serum ALT, AST and ALP levels in TUDCA group and AST levels in UDCA group were significantly reduced as compared with baseline （P〈0.05）. Serum albumin levels were significantly increased in both TUDCA and UDCA groups （P〈0.05）. Serum markers for liver fibrosis were slightly decreased with the difference being not significant in either group. Only one patient in TUDCA group had significantly histological relief. Both treatments were well tolerated and no patient complained of side effects. It is suggested that TUDCA therapy is safe and appears to be more effective than UDCA in the treatment of liver cirrhosis, particularly in the improvement of the biochemical expression. However, both drugs exert no effect on the serum markers for liver fibrosis during 6-month treatment.

Ursodeoxycholic acid combined with percutaneous transhepatic balloon dilation for management of gallstones after elimination of common bile duct stones

AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct(CBD) stones.METHODS From April 2014 to May 2016, 15 consecutive patients(6 men and 9 women) aged 45-86(mean, 69.07 ± 9.91) years suffering from CBD stones associated with gallstones were evaluated. Good gallbladder contraction function was confirmed by type B ultrasonography. Dilation of the CBD and cystic duct was detected. Percutaneous transhepatic balloon dilation of the papilla was performed, ursodeoxycholic acid was administered, and all patients had a high-fat diet. All subjects underwent repeated cholangiography, and percutaneous transhepatic removal was carried out in patients with secondary CBD stones originating from the gallbladder. RESULTS All patients underwent percutaneous transhepatic balloon dilation with a primary success rate of 100%. The combined therapy was successful in 86.7% of patients with concomitant CBD stones and gallstones. No remaining stones were detected in the gallbladder. Transient adverse events include abdominal pain(n = 1), abdominal distension(n = 1), and fever(n = 1). Complications were treated successfully via nonsurgical management without long-term complications. No procedure-related mortality occurred. CONCLUSION For patients with concomitant CBD stones and gallstones, after percutaneous transhepatic removal of primary CBD stones, oral ursodeoxycholic acid and a high-fat diet followed by percutaneous transhepatic removal of secondary CBD stones appear to be a feasible and effective option for management of gallstones.

Ursodeoxycholic acid therapy in gallbladder disease,a story not yet completed

Gallstone disease represents an important issue in the healthcare system.The principal non-invasive nonsurgical medical treatment for cholesterol gallstones is still represented by oral litholysis with bile acids.The first successful and documented dissolution of cholesterol gallstones was achieved in 1972.Since then a large number of investigators all over the world,have been dedicated in biochemical and clinical studies on ursodeoxycholic acid(UDCA),demonstrating its extreme versatility.This editorial is aimed to provide a brief review of recent developments in UDCA use,current indications for its use and,the more recent advances in understanding its effects in terms of an antiinflammatory drug.

Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT/mTOR/SREBP-1 signaling pathway

BACKGROUND Nonalcoholic fatty liver disease(NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis(NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeoxycholic acid(UDCA)play an essential role in the pathogenesis of NAFLD by regulating the level of sterol regulatory element-binding protein(SREBP) 1 c, but the underlying regulatory mechanism remains elusive. Increased evidence indicates that the AKT/mTOR/SREBP-1 signaling pathway is a key pathway to regulate hepatic cellular lipid metabolism. UDCA may regulate the AKT/mTOR/SREBP-1 signaling pathway to ameliorate hepatic lipid metabolism.AIM To investigate the functional mechanism of UDCA in an oleic acid(OA)-induced cellular model of NAFLD.METHODS The cellular model of NAFLD was established using OA and treated with UDCA.First, the best concentration of UDCA was selected. For the best time-dependent assay, cells were stimulated with OA only or co-treated with OA and 2 mmol/L UDCA for 24 h, 48 h, and 72 h. Oil red O staining was used to observe the accumulation of intracellular lipids, while the intracellular contents of triglyceride, alanine aminotransferase(ALT), gamma-glutamyl transpeptidase(GGT), and aspartate aminotransferase(AST) were detected by enzymatic methods. Meanwhile, the expression levels of AKT/mTOR/SREBP-1 signaling pathway-related proteins were detected by real-time PCR and Western blot.RESULTS In the NAFLD cell model established with LO2 cells induced using OA, lipid accumulation was obvious. UDCA significantly inhibited lipid accumulation at different concentrations(especially 2 mmol/L) and decreased cell growth ability at different time points. The biochemical parameters like ALT, AST, and GGT were significant improved by UDCA. UDCA treatment vividly repressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in LO2 cells induced with OA.CONCLUSION Our findings demonstrate the effect of UDCA in improving NAFLD. UDCA attenuates OA-induced hepatic steatosis mainly by regulation of AKT/mTOR/SREBP-1 signal transduction.

Ursodeoxycholic acid as a means of preventing atherosclerosis,steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD therapy.Ursodeoxycholic acid(UDCA),which is one of the first-line therapeutic agents for treatment of NAFLD,is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIM To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests,lipid profile,hepatic steatosis and fibrosis,atherogenesis,and ASCVD risk in men and women with NAFLD,as well as to assess the impact of>5%weight reduction on these parameters.METHODS An open-label,multicenter,international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise.The efficacy criteria were liver enzymes,lipid profile,fatty liver index(FLI),noninvasive liver fibrosis tests(nonalcoholic fatty liver disease fibrosis score and liver fibrosis index),carotid intima-media thickness(CIMT),and ASCVD risk score.To test statistical hypotheses,the Wilcoxon test,paired t-test,Fisher’s exact test,and Pearson's chi-squared test were used.RESULTS The alanine aminotransferase(ALT)level changed by-14.1 U/L(-31.0;-5.3)from baseline to 3 mo and by-6.5 U/L(-14.0;0.1)from 3 to 6 mo.The magnitude of ALT,aspartate transaminase,and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo(P<0.001,P<0.01,P<0.001,respectively).At 6 mo,in the total sample,we observed a statistically significant decrease in body weight and levels of FLI:84.9±10.4 vs 72.3±17.6,P<0.001,total cholesterol:6.03±1.36 vs 5.76±1.21,Р<0.001,lowdensity lipoprotein:3.86±1.01 vs 3.66±0.91,Р<0.001,and triglyceride:3.18(2.00;4.29)vs 2.04(1.40;3.16),Р<0.001.No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found.The CIMT decreased significantly in the total sample(0.985±0.243 vs 0.968±0.237,P=0.013),whereas the highdensity lipoprotein(Р=0.036)and 10-year ASCVD risk(Р=0.003)improved significantly only in women.Fifty-four patients(31%)achieved>5%weight loss.At the end of the study,the FLI decreased significantly in patients with(88.3±10.2 vs 71.4±19.6,P<0.001)and without>5%weight loss(83.5±10.3 vs 72.8±16.7,P<0.001).The changes in ALT,aspartate transaminase,glutamyltransferase,total cholesterol,and low-density lipoprotein levels were similar between the subgroups.CONCLUSION UDCA normalizes liver enzymes greatly within the first 3 mo of treatment,improves lipid profile and hepatic steatosis independent of weight loss,and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.

Clinical usefulness of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis

AIM To evaluate the therapeutic effects of ursodeoxycholic acid(UDCA) on autoimmune hepatitis(AIH).METHODS A total 136 patients who were diagnosed with AIH were included in our study. All of the patients underwent a liver biopsy, and had at least a probable diagnosis on the basis of either the revised scoring system or the simplified scores. Initial treatment included UDCA monotherapy(Group U, n = 48) and prednisolone(PSL) monotherapy(Group P, n = 88). Group U was further classified into two subgroups according to the effect of UDCA: Patients who had achieved remission induction with UDCA monotherapy and showed no sign of relapse(Subgroup U1, n = 34) and patients who additionally received PSL during follow-up(Subgroup U2, n = 14). We compared the clinical and histological findings between each groups, and investigated factorscontributing to the response to UDCA monotherapy.RESULTS In Group U, 34 patients(71%) achieved and maintained remission over 49(range: 8-90) mo(Subgroup U1) and 14 patients(29%) additionally received PSL(Subgroup U2) during follow-up. Two patients in Subgroup U2 achieved remission induction once but additionally required PSL administration because of relapse(15 and 35 mo after the start of treatment). The remaining 12 patients in Subgroup U2 failed to achieve remission induction during follow-up, and PSL was added during 7(range: 2-18) mo. Compared with Subgroup U2, Subgroup U1 had significantly lower alanine aminotransferase(ALT) levels at onset(124 IU/L vs 262 IU/L, P = 0.023) and a significantly higher proportion of patients with mild inflammation(A1) on histological examination(70.6% vs 35.7%, P = 0.025). When multivariate analysis was performed to identify factors contributing to the response to UDCA monotherapy, only a serum ALT level of 200 IU/L or lower was found to be associated with a significant difference(P = 0.013).CONCLUSION To prevent adverse events related to corticosteroids, UDCA monotherapy for AIH needs to be considered in patients with a serum ALT level of 200 IU/L or lower.

Protective effects of Balanites aegyptiaca extract, melatonin and ursodeoxycholic acid against hepatotoxicity induced by methotrexate in male rats

Objective: To compare the degree of ameliorative effects of Melatonin(MEL), Ursodeoxycholic acid(UDCA) and Balanites aegyptiaca(BA) against hepatotoxicity induced by MTX for one month. Methods: Eighty adult male rats(Sprague Dawely) weighing(190±10g), were randomly divided into eight equal groups: Control, MTX, MEL, BA, UDCA, MTX+MEL, MTX+BA, MTX+UDCA. Liver function biomarker enzymes, liver tissue oxidative stress parameters, together with total antioxidant capacity and tumor necrosis factor(TNF-α) were determined. Histopathological and immunohistochemistry examinations for TNF-α were also done. Results: MTX showed significant increase in alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), gamma glutamyl transferase(GGT), total and direct bilirubin, as well as TNF-α levels, oxidized glutathione(GSSG), malodialdehyde(MDA) and nitric oxide(NO). whereas, total protein, albumin, total antioxidant capacity, reduced glutathione(GSH), glutathione peroxidase(GPx), glutathione reductase(GR), glutathione S-transferase(GST), superoxide dismutase(SOD) and catalase(CAT) levels were significantly decreased in MTX treated group. These alterations were improved by MEL and BA treatment, whereas no improvement was noticed in UDCA treatment. Conclusions: BA may be as promising as MEL in the hepatoprotection against MTX toxicity through their antioxidant and radical scavenging activities. In addition, it is not recommended to co-administer UDCA with MTX as it enhanced inflammation and damage to the liver.

Ursodeoxycholic Acid in the Treatment of Intraheptic Cholestasis of Pregnancy

In order to observe the effect of ursodeoxycholic acid （UDCA） in the treatment of intrahepatic cholestasis of pregnancy （ICP）, 68 patients with ICP were equally divided into treatment group and control group at random. The patients in treatment group were administered with UDCA 300 mg three times every day and those in control group received a combination of 10 % glucose, Vitamin C and Inosine. Itching scores, serum ALT and total bile acids （TBA） were measured before, during and after treatment. The results showed that as compared with those before treatment, itching scores, serum ALT and TBA were significantly reduced after treatment （P〈0.05）. The occurrences of premature labor, fetal asphyxia and meconium staining in amniotic fluid were significantly lower in treatment group than in control group （P〈0. 05）. It was suggested that UDCA was an effective drug in the treatment of ICP.

The therapeutic efficiency of ursodeoxycholic acid on Gilbert syndrome complicated by aplastic anemia: a series of case reports

Objective:To reduce the potential risk in aplastic anemia patients complicated with Gilbert syndrome,and find an effective treatment for the unconjugated hyperbilirubinemia.Material and Methods:The mutation of UGT1A1 gene was identified first via sequencing in patients with Gilbert syndrome complicated by aplastic anemia.Before the treatment for aplastic anemia,bilirubin and phenobarbitone tests were conducted.Patients were then treated for their primary disease and given ursodeoxycholic acid(UDCA)either with or without phenobarbitone.Results:The clinical practice of UDCA,which can alleviate increased bilirubin levels,did not affect the key treatments for aplastic anemia.Conclusions:These results indicate that Gilbert syndrome should be addressed when treating aplastic anemia.Furthermore,abnormal bilirubin levels can be controlled effectively by the UDCA treatment.

Anti-Tuberculosis Drug Induced Liver Injury and Ursodeoxycholic Acid

Hepatotoxicity induced by standard anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide) can result in significant morbidity and, rarely, even mortality. This major adverse side-effect of anti-tuberculosis treatment has a negative impact on patient adherence and patient outcomes as well as on tuberculosis control. Early recognition and prompt withdrawal of the offending drugs are the most critical interventions in the management of anti-tuberculosis drug-induced liver injury. No drug or herbal extract has been shown until recently to prevent or reverse anti-tuberculosis drug-induced hepatotoxicity. Ursodeoxycholic acid is the only FDA approved drug for the treatment of primary biliary cholangitis and has also been successfully used in various cholestatic liver diseases. Although still experimental, recent controlled clinical studies suggested that oral administration of ursodeoxycholic acid may prevent the onset of anti-tuberculosis drug-induced liver injury and accelerate the recovery of liver injury. These clinical data are supported by experimental models of anti-tuberculosis drug-induced hepatotoxicity. There is an urgent need for further randomized clinical trials to document the promising hepatoprotective properties of ursodeoxycholic acid.

Effect of ursodeoxycholic acid combined with bifidobacterium quadruple preparations on myocardial enzyme, immune function and inflammatory response of hyperbilirubinemia neonatal

Objective: To investigate the effects of myocardial enzyme, immune function and inflammatory response by ursodeoxycholic acid combined with bifidobacterium quadruple preparations on hyperbilirubinemia neonatal. Methods: A total of 100 cases of neonatal hyperbilirubinemia in our hospital from June 2016 to May-2017 were selected and divided into control group and observation group by random number table, 50 cases in each group. Two groups of neonatal were given routine symptomatic treatment. The control group was treated with ursodeoxycholic acid and the observation group was treated with Bifidobacterium tetralogy of live bacteria on the basis of the control group. The two groups of neonatal were both treated for 7 d. The serum levels of CK-MB, CK, LDH, AST, CD3+, CD4+, CD4+/CD8+, CD8+, CRP and TNF-α were measured before and after the treatment of the two groups. Results: Before treatment, there was no significant difference in serum CK-MB, CK, LDH, AST, CD3+, CD4+, CD4+/CD8+, CD8+, CRP and TNF-α levels between the 2 groups. After treatment: 2 groups of serum CK-MB, CK, LDH, AST, CD8+, CRP, TNF-α levels significantly decreased compared with the group before treatment, CD3+, CD4+ and CD4+/CD8+ levels were significantly increased after treatment, and the observation group with serum CK-MB, CK, LDH, AST, CD8 +, CRP, TNF-α levels were significantly lower than the control group, CD3+, CD4+ and CD4+/CD8+ levels were significantly higher than the control group, the differences were statistically significant. Conclusion: Ursodeoxycholic acid combined with Bifidobacterium quadruple viable tablets can can reduce the activity of myocardial enzyme, improve the state of spectrum index of neonatal hyperbilirubinemia.

Thermal Decomposition Kinetics of Ursodeoxycholic Acid Drug Crystal

The crystallization of ursodeoxycholic acid drug crystals in gel by reduction of solubility method is the first of its kind to be reported in literature. Monoclinic crystalline form of the structure was confirmed using single crystal X-ray diffraction analysis. This report deals with the kinetic analysis made from the thermogravimetric analysis/differential thermal analysis (TGA/DTA) data using Coats-Redfern (CR) relation. Thermodynamic parameters were also determined. Arrhenius equation for ursodeoxycholic acid was derived as k = 3.10 × 1010 e&minus;172581/RT mol&minus;1&bull;s&minus;1.

Efficacy of ursodeoxycholic acid as an adjuvant treatment to prevent acute cellular rejection after liver transplantation: a meta-analysis of randomized controlled trials

BACKGROUND： Acute cellular rejection（ACR） after liver transplantation（LT） is one of the most common problems faced by transplant recipients in spite of advances in immunosuppressive therapy. Recently, clinical trials reported that ursodeoxycholic acid（UDCA） reduced the incidence of ACR significantly.However, others have shown contradictory conclusion. Therefore,we performed a meta-analysis of rigorous randomized controlled trials（RCTs） to determine the efficacy of UDCA in reducing ACR after LT.DATA SOURCES： All RCTs that evaluated efficacy of UDCA as an adjuvant treatment to prevent ACR after LT were searched from PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect databases and Web of Science（from January 1981 to March 2012）. There was no language limitation in these searches. Relevant abstracts of international meetings were also searched. References of each included study were searched manually.RESULTS： A total of 234 patients from four high-quality RCTs（Jadad score 4 to 5） were included in this meta-analysis.Prophylactic use of UDCA did not decrease the incidence of ACR（RR： 0.94, 95% CI： 0.77-1.16, P0.05）, steroid-resistant rejection（RR： 0.77, 95% CI： 0.47-1.27, P0.05） and the number of patients with the multiple episodes of ACR（RR： 0.60, 95% CI：0.28-1.30, P0.05）. Different intervention programs（high-dose vs low-dose UDCA; early vs delayed UDCA treatment） also did not alter the outcomes.CONCLUSIONS： UDCA, as an adjuvant treatment, was not ableto prevent ACR and steroid-resistant rejection after LT. Further trials should be done to determine whether higher dose of UDCA will be beneficial.

Effects of low molecular heparin combined with ursodeoxycholic acid on liver function, immunologic function and pregnancy outcome in patients with intrahepatic cholestasis of pregnancy

Objective: To investigate the effects of low molecular heparin (LMWH) combined with ursodeoxycholic acid (UDCA) on liver function, immunologic function and pregnancy outcome in patients with intrahepatic cholestasis of pregnancy (ICP). Methods: A total of 110 patients with ICP were randomly divided into the observation group (n=55) and the control group (n=55). Patients in the control group received conventional therapy, while patients in the observation group were treated with LMWH hypodermic injection and UDCA orally on the basis of the treatment plan of the control group. Before and after treatment, the levels of serum total bile acid (TBA), glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP) and immunoglobulin (IgG, IgA, IgM) between the two groups were compared. The changes of T lymphocyte subsets of peripheral blood in the two groups were analyzed, and the pregnancy outcomes of the two groups were observed. Results: After treatment, the serum levels of TBA, ALT, AST, TBIL, DBIL and ALP in the two groups were significantly lower than those before treatment, and the change of each index in the observation group was more obvious than that in the control group. The serum levels of IgG, IgA and IgM in the observation group after treatment were significantly higher than those before treatment and those in the control group after treatment. However, the percentage of CD4+T cells and the ratio of CD4+/CD8+ in the observation group after treatment were significantly lower than those before treatment and those in the control group after treatment. Conclusions: LMWH combined with UDCA could effectively reduce serum bile acid level, improve liver function and regulate immune balance in patients with ICP, and improve outcomes of maternal and fetal.

Can Ursodeoxycholic Acid Prevent SARS-CoV-2 Infection or Reduce the COVID-19 Severity? Current Knowledge and Unresolved Issues

A recent study revealed that the inhibition of the farnesoid X receptor using ursodeoxycholic acid(UDCA)significantly reduces angiotensin-converting enzyme 2(ACE2)expression.Therefore,considerable attention has been paid to the use of UDCA to prevent severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and reduce the severity of the disease.This review compre-hensively summarizes the role of ACE2 in SARS-CoV-2 infection and the potential role and mechanisms of UDCA in the prevention of SARS-CoV-2 infection or reinfection.It also discusses unresolved issues and the potential use of UDCA in the treatment of patients with coronavirus disease.

Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases

Most neurodegenerative disorders are diseases of protein homeostasis, with misfolded aggregates accumulating. The neurodegenerative process is mediated by numerous metabolic pathways, most of which lead to apoptosis. In recent years, hydrophilic bile acids, particularly tauroursodeoxycholic acid (TUDCA), have shown important anti-apoptotic and neuroprotective activities, with numerous experimental and clinical evidence suggesting their possible therapeutic use as disease-modifiers in neurodegenerative diseases. Experimental evidence on the mechanisms underlying TUDCA’s neuroprotective action derives from animal models of Alzheimer’s disease, Parkinson’s disease, Huntington’s diseases, amyotrophic lateral sclerosis (ALS) and cerebral ischemia. Preclinical studies indicate that TUDCA exerts its effects not only by regulating and inhibiting the apoptotic cascade, but also by reducing oxidative stress, protecting the mitochondria, producing an anti-neuroinflammatory action, and acting as a chemical chaperone to maintain the stability and correct folding of proteins. Furthermore, data from phase II clinical trials have shown TUDCA to be safe and a potential disease-modifier in ALS. ALS is the first neurodegenerative disease being treated with hydrophilic bile acids. While further clinical evidence is being accumulated for the other diseases, TUDCA stands as a promising treatment for neurodegenerative diseases.

Effect of ursodeoxycholic acid on TGF betal/Smad signaling pathway in rat hepatic stellate cells

Background Hepatic fibrosis is the key stage of the pathological progress from hepatic injury to cirrhosis. Ursodeoxycholic acid （UDCA） has been known as having significant clinical therapeutic effects on chronic liver diseases. Our research aimed to study the effect of UDCA on the signaling pathway of transforming growth factor beta1 （TGFβ1）/Smad and discuss its possible molecular mechanisms of inhibiting hepatic fibrosis. Methods Rat hepatic stellate cells were cultured in vitro and randomly assigned to 4 groups. Group A was control group with only DMEM culture medium applied, and groups B, C, D were experimental groups, with different doses of UDCA （1.0 mmol/L, 0.5 mmol/L and 0.25 mmol/L respectively） added into their DMEM culture medium for further culture of 24 hours and 48 hours. The protein expressions of TGFβ1, TGF type 1 receptor, Smad3, Smad4 and Smad7 were measured by Western blotting, as well as the expressions of TGFβ1, Smad3, Smad7 and cAMP response element （CREB） binding protein （CBP） mRNA by real-time PCR. SPSS 11.5 statistical package was adopted for data analyses. Results Compared with control group, the mRNA expressions of TGFβ1 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly decreased （P 〈0.05）, the protein expressions of TGFβ1 in the two above groups for 48 hours and in the high dose group for 24 hours significantly decreased （P 〈0.05）. The protein and mRNA expressions of Smad3 in each UDCA dose group for 24 hours and 48 hours significantly decreased, with significant difference among different UDCA dose groups and between that of 24 hours and 48 hours observed （P 〈0.05）. The protein and mRNA expressions of Smad7 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly increased. The CBP mRNA expression in each UDCA dose group for 24 hours and 48 hours significantly decreased （P 〈0.05）, with significant difference among different UDCA dose groups observed （P 〈0.05）. Conclusion UDCA could curb the development of hepatic fibrosis through affecting the signaling pathway of TGFβ1/Smad by inhibiting the expressions of TGFβ1, Smad3 and CBP and increasing the expression of Smad7.