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Background: Ursodeoxycholic acid (UDCA), a bile acid, protects the liver through various mechanisms, including bile composition modulation and enhanced secretion. In ALL chemotherapy, 6MP is hepatotoxic, requiring dose reduction. UDCA is used to alleviate liver toxicity in ALL and other chronic cholestatic conditions. The study aims to evaluate the effectiveness of UDCA with chemotherapy in reducing 6MP treatment interruptions and its impact on treatment continuity in pediatric ALL.Methods: This randomized controlled trial study conducted at the Department of Pediatric Hematology and Oncology, BSMMU in pediatric ALL patients during chemotherapy from September 2018 to August 2019. Fifty children aged 1 to 18 years with ALL were enrolled, half receiving UDCA alongside chemotherapy and the rest forming the control group. Serum hepatic transaminases, total bilirubin, and CBC were monitored every 14 days. Statistical analysis was performed using SPSS, with significance set at p<0.05.Results: In this study of 50 pediatric ALL patients, there were no statistically significant age or gender differences between the "Case" (UDCA-treated) and "Control" groups. However, the UDCA group showed a significant decrease in abnormal liver function tests (32.0%) compared to controls (60.0%). Moreover, 6MP dose reduction was significantly lower in cases (4.0%) than controls (40.0%), indicating UDCA's potential hepatoprotective effects. Multivariate logistic regression revealed male gender and mean AST levels as significant factors associated with hepatotoxicity in pediatric ALL patients.Conclusions: Co-administration of UDCA with chemotherapy demonstrates a significant effect in treatment interruption by hepatotoxic drug specially 6 MP in pediatric ALL patients.

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Primary sclerosing cholangitis （PSC） is a cholestatic disease characterized by chronic progressive bile duct inflammation and has a low incidence rate and poor prognosis in China. There is still no drug therapy that can change the course of PSC， and liver transplantation is the only effective treatment for PSC， with a 5-year survival rate of 85% after transplantation. Drug therapy for PSC is facing great challenges based on the current status of PSC. At present， drugs for the treatment of PSC are in the stage of clinical trials and have shown certain application prospect， among which ursodeoxycholic acid is the most widely studied and commonly used drug. In addition， there are many emerging drugs in the pipeline. This article summarizes the latest advances in drug therapy for PSC.

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ObjectiveTo investigate the potential effect of ursodeoxycholic acid （UDCA） in the prevention and treatment of COVID-19 in patients with chronic hepatitis B. MethodsClinical data were collected from 324 patients with chronic hepatitis B who were treated in Beijing Ditan Hospital， Capital Medical University， from January to December 2022， and according to whether UDCA was administered， they were divided into UDCA group and control group. The propensity score matching （PSM） method was used to balance the confounding factors such as age， sex， and chronic complications， and the two groups were compared in terms of SARS-CoV-2 infection rate， symptoms， and recovery time after COVID-19. The two groups were also compared in terms of related laboratory markers （white blood cell count ［WBC］， hemoglobin ［Hb］， platelet count ［PLT］， alanine aminotransferase ［ALT］， aspartate aminotransferase ［AST］， albumin ［Alb］， alkaline phosphatase ［ALP］， total bilirubin ［TBil］， triglyceride ［TG］， and total cholesterol ［TC］）， vaccination， and the incidence rate of liver disease symptoms after COVID-19. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of data with skewed distribution between the two groups； the chi-square test and the continuously corrected chi-square test were used for comparison of categorical data between two groups. The binary Logistic regression model was used for univariate and multivariate analyses to investigate the influencing factors for COVID-19 after matching. ResultsThere were 87 patients in the UDCA group and 237 patients in the control group， and after PSM， there were 78 patients in the UDCA group and 137 patients in the control group， with good balance between the two groups. There was a significant difference in SARS-CoV-2 infection rate between the UDCA group and the control group ［82.1% （64/78） vs 95.6% （131/137）， χ2=10.847， P=0.001］. After COVID-19， compared with the control group， the UDCA group had a significantly lower proportion of the patients with chill （10.9% vs 38.9%， χ2=16.124， P<0.001） and cough （56.3% vs 74.8%， χ2=6.889， P=0.009）. There was a significant difference between the UDCA group and the control group in the proportion of the patients with a recovery time of ≤7 days after COVID-19 （79.7% vs 61.1%， χ2=6.760， P=0.009）. Both univariate and multivariate logistic regression analyses showed that UDCA was an independent influencing factor for COVID-19 （odds ratio=0.21 and 0.17， both P<0.05）. ConclusionUDCA is an protective factor against COVID-19 in patients with chronic hepatitis B and can alleviate related symptoms to some extent and shorten the recovery time， and therefore， it has an important value in the prevention and treatment of COVID-19.

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ObjectiveTo investigate the value of baseline red cell distribution width （RDW） and alkaline phosphatase （ALP） level after ursodeoxycholic acid （UDCA） treatment for one month in predicting the response to UDCA treatment in patients with primary biliary cholangitis （PBC）. MethodsA retrospective analysis was performed for the data of 127 patients with PBC who were diagnosed in Department of Hepatology， The Third People’s Hospital of Jiangsu University， from January 2015 to July 2022， with data collected at baseline， after one month of treatment， and after one year of follow-up. Based on the Paris-I criteria， the patients were divided into good response group and poor response group， and the two groups were analyzed in terms of clinical and laboratory features and their association with response to UDCA. The Logistic regression method was used to investigate the independent risk factors for response to UDCA treatment. The area under the ROC curve （AUC） was used to determine the optimal cut-off values of related indicators； the patients were divided into two groups based on such values， and the two groups were compared in terms of baseline indicators and response. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the good response group， the poor response group had significantly higher levels of total bilirubin， aspartate aminotransferase/alanine aminotransferase， ALP， RDW， and RDW-CV at baseline and a significantly higher level of ALP after one month of UDCA treatment （Z=-4.792， -3.697， -2.399， -4.102， -3.220， and -4.236， all P<0.05）. Compared with the good response group， the poor response group had significantly lower levels of albumin， hemoglobin， lymphocytes， hematocrit， and body mass index at baseline （Z=-3.592， -3.603， -2.602， -3.829， -2.432， all P<0.05）， as well as significantly lower levels of prealbumin， albumin/globulin ratio， apolipoprotein A， and free triiodothyronine at baseline （t=4.530， 3.402， 3.485， and 3.639， all P<0.001）. Compared with the poor response group， the good response group had a significantly lower proportion of patients with liver cirrhosis， gallstones/cholecystitis， or anemia （χ2=20.815， 3.892， and 12.283， all P<0.05）. Baseline RDW （odds ratio ［OR］=1.157， 95% confidence interval ［CI］： 1.028‍ — ‍1.301， P=0.015） and ALP level after one month of treatment （OR=1.012， 95%CI： 1.005‍ — ‍1.020， P=0.002） were independent risk factors for response to UDCA， with an AUC of 0.713 and 0.720， respectively. The patients with baseline RDW≥upper limit of normal （ULN） and ALP≥2.2×ULN after one month of UDCA treatment had a lower UDCA response rate （42.6% vs 8.2%， χ2=20.813， P<0.001）. ConclusionPatients with baseline RDW≥ULN and ALP≥2.2×ULN after one month of UDCA treatment tend to have a low biochemical response rate to UDCA.

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Introduction: Intrahepatic cholestasis of pregnancy (IHCP) is associated with an increased risk of adverse fetal outcome, for example, prematurity, meconium-stained amniotic fluid, perinatal hypoxia, and sudden intrauterine fetal death. The exact mechanism of cholestasis-induced fetal complications is not yet fully understood. The aim of the present study was to evaluate and compare the histopathological changes in the placentas of patients with IHCP and healthy pregnant women, and to see the correlation with adverse fetal outcomes with these histopathological changes of IHCP. Material and Methods: The effect of IHCP on the placental microstructure was investigated using placental tissue from patients with IHCP treated with ursodeoxycholic acid (UDCA) and from healthy pregnancies. Seven placental histopathological features were analyzed: Increased calcification, increased syncytial knots, trophoblastic cell proliferation, fibrinoid necrosis, perivascular fibrinoid deposition, terminal villous capillarization, and features of chorioamnionitis. Results: There were significant differences in placental histopathology of increased syncytial knots, fibrinoid necrosis, perivascular fibrinoid deposition, and terminal villous capillarization in IHCP patients treated with UDCA and in patients with uncomplicated pregnancy. However, in the control group, the rate of neonatal intensive care unit admission was significantly associated with trophoblastic cell proliferation (P = 0.009). Conclusions: Various histopathological features suggestive of placental inflammation are seen more in cases as compared to controls.

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Intrahepatic cholestasis of pregnancy (ICP) also known as obstetric cholestasis is a liver disorder of pregnancy which is characterised by maternal pruritus usually in the third trimester, raised serum bile acids and increased incidence of adverse fetal outcomes and usually complete resolution of symptoms post-delivery. The etiology of ICP is complex and multifactorial as is the mechanism by which fetal complications occur which is yet not completely understood. The introduction of ursodeoxycholic acid in the management of ICP has provided significant improvement in maternal symptoms as well as fetal outcome. We present a case series of 5 cases of obstetric cholestasis which presented in our tertiary care hospital which could possibly help and guide obstetricians in the future who are dealing with dilemma in diagnosis and management of this condition.

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Introduction: This present study is about the GC MS analysis of one important Siddha formulation, Nilavembu Kudineer.Methods: Nilavembu Kudineer powder was obtained from standard Siddha medical vendor at Chennai, India and was suitably processed for GC MS analysis.Results: Some important biomolecules such as Z-(13,14-Epoxy)tetradec-11-en-1-ol acetate, piperine, ursodeoxycholic acid, ethyl iso-allocholate, 9,19-cyclolanostan-3-ol, 24,24-epoxymethano, acetate and hexadecanoic acid, 2-(hexadecyloxy)ethyl ester were observed in the GC MS profile which are found to have medicinal roles that are far reaching, which supports this medicine as an effective formulation towards the cure of many inflammatory diseases.Conclusion: This medicine, due to the presence of medicinally important molecules indicates its effectiveness as a potent medicine for which it is usually prescribed.

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Background: Chronic cholestatic liver disease (CCLD) constitutes an intricate array of liver diseases in India. A physician-based survey was conducted to understand the prevalence, current treatment approaches, and gaps in themanagement of CCLD in India.Methods: A total of 215 physicians participated to complete a questionnaire comprising 35 questions related to the prevalence and current treatment of CCLD and assess gaps in its management.Results: Most physicians (53.5%) reported liver disorders with cholestasis to be prevalent in 10-20% of patients,while 34.9% reported their prevalence in 21-30% of patients. Alcoholic liver disease with cholestasis (CCLD [ALD])was reported in 10-20% of patients and 21-30% of patients by 33.5% and 37.2% of physicians, respectively. Druginduced liver disease with cholestasis (CCLD [DILI]) was reported to be present in 5-10% of patients by 34.9% of physicians. Ursodeoxycholic acid (UDCA) was found to be used by 60% physicians in >50% of patients with CCLD(ALD), commonly for a period of 4-12 weeks (48.4% physicians), while it was used for 12-24 weeks by 38.1% physicians in CCLD (DILI); for both conditions, the preferred dose was 10-15 mg/kg body weight. UDCA was reported to have good tolerability and efficacy by most physicians for both conditions.Conclusions: In light of scarce data on CCLD prevalence and management approaches in India, the present surveyfindings provide useful insights on its prevalence in India and support the use of UDCA therapy for the management of its symptoms.

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OBJECTIVE To compare the efficacy of Danning tablet， taurosodeoxycholic acid and ursodeoxycholic acid in preventing the recurrence of choledocholithiasis after endoscopic retrograde cholangiopancreatography （ERCP）. METHODS The clinical data of 153 patients who underwent ERCP choledocholithotomy from January 2017 to January 2020 in Nantong First People’s Hospital were retrospectively analyzed. According to the different drug treatment received after surgery， patients were divided into three groups， namely， Danning tablet group （group A， 49 cases）， tauroursodeoxycholic acid group （group B， 44 cases） and ursodeoxycholic acid group （group C， 60 cases）. The above groups of drugs are all single-use， starting from 2 weeks after surgery for a course of 180 days. The effects of bile component indicators [total bilirubin （Tbil）， direct bilirubin （Dbil）， alkaline phosphatase （ALP）， glutamyltransferase （GGT）]， lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， the occurrence of clinical symptoms （abdominal pain， bloating， nausea， and poor appetite） at 6 months after ERCP， and the recurrence of choledocholithiasis at 6， 12， 18 and 24 months after surgery were compared among 3 groups. RESULTS Compared with before surgery， the serum levels of Tbil， Dbil， ALP， GGT， TC， TG and LDL were significantly reduced （P＜0.05）， while serum HDL levels were significantly increased （P＜0.05） in the three groups at 6 months after surgery. The proportion of patients who experienced abdominal pain， bloating， nausea， and poor appetite at 6 months after surgery was significantly reduced （P＜0.05）. The Tbil levels of groups A and B were significantly lower than those of group C （P＜0.05）， while the Dbil and ALP levels of group A were significantly lower than those of groups B and C （P＜0.05）； however， there was no statistically significant difference in GGT levels among the 3 groups （P＞0.05）. Compared with groups A and C， the levels of four lipid metabolism indicators in group B were significantly improved （P＜0.05）； the proportion of patients with abdominal pain， bloating， and poor appetite in group A was significantly lower than groups B and C （P＜0.05）， but there was no statistically significant difference in the proportion of patients with nausea among the 3 groups （P＞0.05）. At 6，12 and 18 months after surgery， there was no statistically significant difference in the rate of choledocholithiasis recurrence among the 3 groups （P＞0.05）； at 24 months after surgery， the rate of choledocholithiasis recurrence in group A （2.04%） was significantly lower than group B （15.91%） and group C （15.00%） （P＜0.05）. CONCLUSIONS Compared with tauroursodeoxycholic acid and ursodeoxycholic acid， the application of Danning tablet after ERCP is more beneficial to reduce the secretion of bile acid， prevent the recurrence of gallstones， and improve clinical symptoms， but tauroursodeoxycholic acid can significantly accelerate the lipid metabolism of patients compared with the other two drugs.

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Objective To investigate the epidemiological characteristics of SARS-CoV-2 pneumonia in kidney transplant recipients and analyze the risk and protective factors of severe/critical infection with SARS-CoV-2. Methods Clinical data of 468 kidney transplant recipients infected with SARS-CoV-2 were retrospectively analyzed. According to the severity of infection, they were divided into mild SARS-CoV-2 infection recipients (n=439) and SARS-CoV-2 pneumonia group (n=29). Among the 439 mild SARS-CoV-2 infection recipients, 87 recipients who were randomly matched with their counterparts in the SARS-CoV-2 pneumonia group according to sex, age and transplantation time at a ratio of 3∶1 were allocated into the mild SARS-CoV-2 infection group. Twenty-nine recipients in the SARS-CoV-2 pneumonia group were divided into the moderate SARS-CoV-2 pneumonia group (n=21) and severe/critical SARS-CoV-2 pneumonia group (n=8). Baseline data of all recipients were collected. The risk and protective factors of SARS-CoV-2 infection in kidney transplant recipients were identified. Results The proportion of recipients complicated with 2-3 types of complications in the SARS-CoV-2 pneumonia group was higher than that in the mild SARS-CoV-2 infection group, and the proportion of recipients treated with tacrolimus(Tac)+mizoribine+glucocorticoid immunosuppression regimen in the SARS-CoV-2 pneumonia group was lower than that in the mild SARS-CoV-2 infection group, and significant differences were observed (both P<0.05). In 29 kidney transplant recipients with SARS-CoV-2 pneumonia in the SARS-CoV-2 pneumonia group, white blood cells, the absolute values of lymphocytes, eosinophils, total T cells, CD4+T cells and CD8+T cells, and serum uric acid levels were significantly lower, whereas ferritin levels were significantly higher than the values prior to SARS-CoV-2 pneumonia, and significant differences were observed (all P<0.05). Compared with the moderate SARS-CoV-2 pneumonia group, the proportion of recipients with hypoxemia was higher, the proportion of recipients treated with Tac/ciclosporin (CsA)+mycophenolate mofetil+glucocorticoid immunosuppression regimen was higher, and the proportion of recipients administered with 2-3 doses of SARS-CoV-2 vaccine was lower in the severe/critical SARS-CoV-2 pneumonia group, and significant differences were observed (all P<0.05). Conclusions More complications and immunosuppression regimen containing mycophenolate mofetil are the risk factor for SARS-CoV-2 infection in kidney transplant recipients. Vaccination with SARS-CoV-2 vaccine and immunosuppression regimen containing mizoribine are probably the protective factors for lowering the risk of SARS-CoV-2 infection. The levels of inflammatory cytokines are associated with the severity of SARS-CoV-2 pneumonia.

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Objective:To analyze the mechanism of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstone and cholecystitis based on network pharmacology; To conduct a comparative analysis.Methods:The chemical components of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid and their drug targets were collected from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). DAVID 6.8 database was used to search for the associated diseases of the drug targets. The disease targets of gallstone and cholecystitis were collected from GeneCards and other databases. The protein-protein interactions network was established based on the intersecting targets of three drugs and two diseases. KEGG enrichment analysis was performed based on the DAVID 6.8 database. Cytoscape 3.7.1 software was used to construct a complex network and topology analysis of component- target- disease between three drugs and diseases.Results:222 chemical components and 3 133 drug targets were collected for Jindan Tablets. 104 chemical components and 1 425 action targets were collected for Xiaoyan Lidan Tablets. 1 chemical component and 119 action targets were collected for ursodeoxycholic acid. The three drugs were associated with 31 diseases. 1 382 disease targets for gallstones and cholecystitis were collected. There were 237, 163 and 33 targets for gallstones and cholecystitis in the three drugs, of which 17 were shared by the three drugs and 20 were shared by Jindan Tablets and Xiaoyan Lidan Tablets. Based on the DAVID database, 113, 74 and 10 significant KEGG enrichment pathways were obtained for the three drugs respectively.Conclusions:The three drugs shared many targets and pathways in the treatment of gallstones and cholecystitis, which all had the function of regulating metabolism and inhibiting inflammatory response, while participating in apoptosis, oxidative stress and cancer pathology process. However, they had their own special effects, with Jindan Tablets favoring involving in the cancer process and inhibition of inflammation, and promoting angiogenesis. Xiaoyan Lidan Tablets and ursodeoxycholic acid focused on regulating cholesterol metabolism, and Xiaoyan Lidan Tablets also regulated steroid metabolism and inhibit inflammation, while ursodeoxycholic acid regulated bile acid metabolism.

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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.

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Objective:To analyze the incidence of gallstone formation after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) by meta-analysis.Methods:English terms for this meta-analysis included "bariatric surgery, gastric bypass, Roux-n-Y gastric bypass, RYGB, sleeve gastrectomy, SG, cholelithiasis, cholecystectomy, gallstone". Researched articles in Pubmed, Medline and Embase databases were searched up to February 2023 and retrieved for further analysis. The quality of each article was evaluated with Newcastle-Ottawa Scale (NOS). Generated data were analyzed with Revman 5.4.Results:Nine relevant cohort studies were retrieved for this meta-analysis, including a total of 24 255 RYGB patients and 4 500 SG patients. All articles met the requirements after the quality evaluation of NOS. The meta-analysis results showed that the incidence of postoperative gallstones in RYGB group was higher than that in SG group ( P<0.001). In subgroup analysis, by administering ursodeoxycholic acid (UDCA) for gallstone prevention, the incidence had no difference between the two groups ( P=0.090), while in the study without UDCA, the incidence of gallstones after RYGB was higher than SG ( P=0.005). In the studies with follow-up time no more than 24 months, the incidence of postoperative gallstones in RYGB group was higher than that in SG group ( P=0.050), but there was no statistical difference when following-up beyond 24 months ( P=0.240). Conclusions:Within 2 years after surgery, RYGB patients have more chances to develop gallstones than SG patients. However, beyond 2-year follow-up, there is no difference between the two procedures. Prophylactical utilization of UDCA after RYGB can effectively reduce the incidence of gallstone formation.

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La colangitis biliar primaria es una enfermedad hepática autoinmune que conduce a la destrucción progresiva de los conductos biliares intrahepáticos, lo que aumenta el riesgo de desarrollar cirrosis e hipertensión portal. Actualmente, el ácido ursodesoxicólico es el medicamento de primera línea para el tratamiento de esta entidad. Este medicamento desplaza los ácidos biliares hidrofóbicos y aumenta las concentraciones de ácidos biliares hidrofílicos en la bilis, lo cual favorece la integridad de los conductos biliares, adicionalmente, tiene efectos antiinflamatorios y propiedades inmunomo-duladoras y antiapoptóticas. En los últimos 40 años, numerosos ensayos clínicos han respaldado la eficacia clínica del ácido ursodesoxicólico y su seguridad cuando se utiliza en pacientes con colan-gitis biliar primaria. Se realiza una revisión del ácido ursodesoxicólico en el contexto de colangitis biliar primaria, se describe su historia, mecanismos de acción, efectos secundarios y dosificación. Finalmente, se menciona su uso en situaciones especiales como son el embarazo y la lactancia

Primary biliary cholangitis is an autoimmune liver disease that leads to progressive destruction of intrahepatic bile ducts, increasing the risk of developing cirrhosis and portal hypertension. Currently, ursodeoxycholic acid is the first-line drug for the treatment of this condition. This drug displaces hy-drophobic bile acids and increases concentrations of hydrophilic bile acids in the bile, which favors the integrity of the bile ducts, additionally, it has anti-inflammatory effects and immunoprotective and antiapoptotic properties. Over the past 40 years numerous clinical trials have supported the clinical efficacy of ursodeoxycholic acid and its safety when used in patients with primary biliary cholangitis. A review of ursodeoxycholic acid in the context of primary biliary cholangitis is carried out, and its history, mechanisms of action, side effects and dosage are described. Finally, its use in special situations such as pregnancy and lactation are discussed.

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BACKGROUND: Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. METHODS: We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber's diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. RESULTS: UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber's diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. CONCLUSIONS: Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.

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Introducción: La colangitis biliar primaria es una enfermedad hepática, crónica y progresiva. El tratamiento con ácido ursodesoxicólico ha ampliado la esperanza de vida de estos pacientes. Objetivo: Describir la respuesta terapéutica al ácido ursodesoxicólico en pacientes con colangitis biliar primaria. Métodos: Estudio descriptivo, longitudinal y ambispectivo en pacientes atendidos en el Instituto de Gastroenterología entre septiembre de 2003 y enero de 2020. Se evaluaron variables clínicas, de laboratorio, histológicas y terapéuticas. El análisis de los resultados se realizó con el paquete SPSS. Resultados: Se incluyeron 45 pacientes. Hubo un predominio del sexo femenino (95,6 %) y una mediana de edad de 54 años. Los niveles bajos de aspartato amino transferasa (p=0,009 HR=0,98) y fosfatasa alcalina (p=0,005, HR=0,99), así como la presencia del síndrome de superposición (p=0,046 HR=3,08) se relacionaron con una buena respuesta al ácido ursodesoxicólico. La mayoría de los que no respondieron al tratamiento tenían cirrosis hepática (68 %). No se observaron diferencias en la supervivencia de los pacientes de acuerdo con su respuesta al tratamiento (p =0,585). Conclusiones: La respuesta terapéutica fue efectiva en menos de la mitad de los tratados con ácido ursodesoxicólico. La cirrosis hepática, el síndrome de superposición y los niveles elevados de aspartato amino transferasa y fosfatasa alcalina se asociaron a la mala respuesta terapéutica.

Introduction: Primary biliary cholangitis is a chronic and progressive liver disease. Treatment with ursodeoxycholic acid has extended the life expectancy of these patients. Objective: To describe the therapeutic response to ursodeoxycholic acid in patients with primary biliary cholangitis. Methods: Descriptive, longitudinal and ambispective study in patients treated at the Institute of Gastroenterology between September 2003 and January 2020. Clinical, laboratory, histological and therapeutic variables were evaluated. The analysis of the results was performed with the SPSS package. Results: Forty-five patients were included, with a predominance of female gender (95.6%) and a average age of 54 years. Low levels of aspartate amino transferase (p=0.009 HR=0.98) and alkaline phosphatase (p=0.005, HR=0.99), as well as the presence of overlap syndrome (p=0.046 HR=3.08) were associated with a better response to ursodeoxycholic acid. Less than half of the patients responded to conventional treatment with UDCA (47.7 %), most of the non-responders suffer from liver cirrhosis (68 %). No differences were observed in patient survival according to their response to treatment (p =0.585). Conclusions: Therapeutic response was effective in less than half of those treated with ursodeoxycholic acid. Liver cirrhosis, overlap syndrome, and elevated aspartate amino transferase and alkaline phosphatase levels were associated with poor therapeutic response.

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Background: Hyperbilirubinemia is a common neonatal problem. Phototherapy and exchange transfusion is the conventional treatment for indirect hyperbilirubinemia. In the treatment of cholestatic liver disorders, Ursodeoxycholic acid (UDCA) is a bile acid widely used. Few studies have been conducted using UDCA in indirect hyperbilirubinemia. Aim of the study: This study was planned to assess the additive effect of UDCA on reducing indirect hyperbilirubinemia in neonates receiving phototherapy. Material & Methods:This prospective randomized controlled trial was conducted among neonates with indirect hyperbilirubinemia in the neonatal wards of Bangladesh Shishu Hospital and Institute, Dhaka, Bangladesh from June 2018 to July 2020. Finally, 140 neonates were included in the study. Eligible cases were randomized into two groups by the lottery method. Group A (n=70) received phototherapy and Group B (n=70) received UDCA at a dose of 10 mg/kg/day orally twice daily in addition to phototherapy. Total serum bilirubin levels were measured every 12 hours until serumbilirubinlevel falls below 10 mg/dl and then phototherapy was stopped. Demographic data, clinical features, laboratory parameters, outcome variables, and complications were recorded in a pre-format sheet. CBC with PBF, Total and indirect bilirubin, Blood grouping and Rh and typing, CRP, Reticulocyte count, and Coombs test were obtained at enrolment. Comparison of parameters among themselves was done by unpaired t-test and chi-square test. Analyzed outcomes were: time for resolution of jaundice, total duration of phototherapy, length of hospital stays, and adverse effects of the drug. The two groups did not differ statistically in age, sex or weight. The mean total serum bilirubin level measured at 12, 24, 36, 48, and 60 hours of treatment in group A was 16.10±1.43, 14.76±1.45, 13.34±1.68, 11.84±1.35, and, 10.57±0.74 respectively, and in the group, B was,15.18±1.63, 13.18±2.25, 11.39±1.56, 9.84±0.81 and, 9.44±0.46 respectively (p<0.001). The mean duration of phototherapy (64.11±10.8 vs. 47.18±7.51 hours, p<0.001) and length of hospital stay (2.80 ±0.40 vs. 2.19±0.39 days, p=<0.001).Conclusion:The inclusion of UDCA as an adjuvant to phototherapy is more effective in reducing indirect hyperbilirubinemia in neonates.

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BACKGROUND: Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease, which can progress to cirrhosis. It mainly affects middle-aged women. Its most frequent form of presentation is asymptomatic with biochemical cholestasis and the presence of antimitochondrial antibodies (AMA). AIM: To describe the epidemiological characteristics, clinical presentation and treatment for patients with PBC at a clinical hospital. MATERIAL AND METHODS: Descriptive, observational, retrospective study, carried out between January 2015 and December 2020. Results: 179 patients (158 women) were cared in the study period. At the time of diagnosis, the median age was 54 years (range 24-76), 55% of them were asymptomatic, 45% had fatigue and 28% had pruritus. Positive AMA were present in 65% of patients, antinuclear antibodies (ANA) in 51%, and anti-smooth muscle antibodies (ASMA) in 9%. Immunoglobulin M (IgM) was elevated in 30% of the patients and 50% of patients were biopsied. Splenomegaly and esophageal varices were present in 24 and 22% of patients, respectively. PBC was associated with Sjogren's syndrome in 15%, hypothyroidism in 14%, osteoporosis in 13%, and scleroderma in 8%. CONCLUSIONS: The epidemiological characteristics of our patients agree with those published abroad. Laboratory cholestasis associated with the presence of AMA, currently allows diagnosis without the need for histological study. Ursodeoxycholic acid (UDCA) is the first-line treatment for patients with PBC. The use of biochemical response criteria is essential to identify patients who require other UDCA alternatives for isolated or combined treatment.

ABSTRACT

Poor response or intolerance to ursodeoxycholic acid may occur in the treatment of primary biliary cholangitis (PBC), and after switch to obeticholic acid or fibrates alone or in combination, poor response or intolerance is also observed in some treatment regimens. Clinical studies on obeticholic acid and fibrates will gradually solve these issues, and obeticholic acid/fibrates combined with ursodeoxycholic acid is safe and effective in PBC patients without advanced liver cirrhosis.

ABSTRACT

Objective:To study the efficacy and influencing factors of ursodeoxycholic acid (UDCA) in the treatment of cholesterol gallstone, so as to provide reference for the treatment of cholesterol gallstone by internal medicine.Methods:From March 1, 2017 to March 31, 2018, at outpatient department of gastroenterology of 9 Beijing medical centers including Peking University People′s Hospital, the Sixth Medical Center of PLA General Hospital, Beijing Huaxin Hospital, PLA Rocket Force Characteristic Medical Center, Peking University Aerospace Center Hospital, Beijing Youan Hospital of Capital Medical University and Beijing Tiantan Hospital of Capital Medical University, Beijing Tongren Hospital of Capital Medical University, and Beijing Shijitan Hospital of Capital Medical University, the data of patients with cholesterol gallstone treated by UDCA were collected. The inclusion criteria were that the largest diameter of stone was ≤10 mm and the stone was not detected under X-ray. The treatment plan was taking UDCA orally for 6 months at a dose of 10 mg·kg -1·d -1. The basic information of patients, the ultrasound examination results before treatment and 6 months after treatment, and scores of biliary abdominal pain and dyspepsia symptom were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of the efficacy in gallstrone dissolution by UDCA, and Wilcoxon signed rank test was used for statistical analysis. Results:A total of 215 patients were enrolled. The complete dissolution rate of gallstone was 19.5% (42/215) and partial dissolution rate was 50.7% (109/215), and the total effective rate was 70.2% (151/215). The complete dissolution rate of sandy stone was significantly higher than that of lumped stones (37.0%(17/46) vs. 14.8%(25/169); OR=3.377, 95% confidence interval (95% CI) 1.621 to 7.035, P=0.001). In lumped stones, the complete dissolution rate of the stones with diameter ≤5 mm was significantly higher than that of the stones with diameter >5 mm (37.5%(9/24) vs. 11.0%(16/145); OR=4.837, 95% CI 1.823 to 12.839, P=0.002). The complete dissolution rate of patients with higher body mass index ( OR=0.872, 95% CI 0.764 to 0.995, P=0.043) and longer disease course ( OR=0.942, 95% CI 0.912 to 0.973, P<0.001) was low. The results of multivariate logistic analysis indicated that long disease course of gallstone ( OR=0.940, 95% CI 0.908 to 0.974, P=0.001), rough gallbladder wall ( OR=0.438, 95% CI 0.200 to 0.962, P=0.040) and lumped stone ( OR=0.236, 95% CI 0.101 to 0.550, P=0.001) were independent risk factors of influencing the efficacy of stone dissolution by UDCA. As for lumped stones, the independent risk factors included long disease course of gallstone ( OR=0.926, 95% CI 0.877 to 0.978, P=0.006) and stone diameter >5 mm ( OR=0.142, 95% CI 0.043 to 0.470, P=0.001). After 6 months of UDCA treatment, score of biliary abdominal pain decreased from 0 (0 to 6) to 0 (0 to 0) and the score of dyspepsia symptom decreased from 1 (0 to 2) to 0 (0 to 0), and the differences between before treatment and after treatment were statistically significant ( Z=-8.50, and -9.13, both P<0.001). Conclusions:UDCA has a certain efficacy in cholesterol gallstone dissolution and can ease biliary abdominal pain and dyspepsia symptom. Long disease course of gallstone, rough gallbladder wall and stone diameter >5 mm are independent risk factors of poor efficacy in gallstone dissolution by UDCA.