Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic ...Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.展开更多
To the Editor:Acute cholangitis,also known as ascending cholangitis,is a po-tentially life-threatening condition resulting from the infection and obstruction of the biliary tract[1].Choledocholithiasis,which in-volves...To the Editor:Acute cholangitis,also known as ascending cholangitis,is a po-tentially life-threatening condition resulting from the infection and obstruction of the biliary tract[1].Choledocholithiasis,which in-volves stones in the common bile duct,is the most frequent cause of such infections,leading to partial or complete blockage of the biliary system[2].During acute episodes,patients may present with abdominal pain,high fever,and jaundice,known as Charcot’s triad,and in severe cases,patients may also exhibit signs of shock and depression[3].An episode of cholangitis can be fatal,and if the underlying obstruction is not addressed,the condition may recur,potentially leading to hepatic abscesses or biliary cirrhosis.Other etiologies of cholangitis include benign biliary strictures,bil-iary malignancies,congenital factors,postoperative complications,inflammatory conditions,and rare causes such as pancreatitis,par-asitic invasion of the biliary tract,external compression,thrombo-sis,and iatrogenic factors.Acute cholecystitis due to the migration of Hem-o-lok clips postoperation is rare.Herein we reported a case of acute cholangitis caused by the migration of surgical Hem-o-lok clips into the bile duct six years after laparoscopic left hemihepa-tectomy.展开更多
BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic ...BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.展开更多
BACKGROUND The optimal duration of antimicrobial treatment for acute cholangitis complicated by gram-positive coccus(GPC)bacteremia remains unclear.The Tokyo Guidelines 2018 recommended 14 days of antimicrobial treatm...BACKGROUND The optimal duration of antimicrobial treatment for acute cholangitis complicated by gram-positive coccus(GPC)bacteremia remains unclear.The Tokyo Guidelines 2018 recommended 14 days of antimicrobial treatment following adequate source control measures;however,evidence supporting this recommendation is limited,and deviations from real-world practice are often observed.AIM To evaluate the efficacy and safety of shorter antimicrobial treatments for acute cholangitis complicated by GPC bacteremia.METHODS Adult patients with acute cholangitis complicated by GPC bacteremia who underwent endoscopic retrograde cholangiopancreatography between July 2003 and December 2023 were included.Patients were categorized into two groups based on the duration of effective antimicrobial treatment:(1)Short-course treatment(SCT)(<14 days);and(2)Long-course treatment(LCT)(≥14 days).The outcomes assessed included mortality,recurrence,reinfection with the same organism related to the cholangitis,and length of hospital stay.RESULTS A total of 44 patients were included in the study:(1)19 patients in the SCT group;and(2)25 patients in the LCT group.The median duration of antimicrobial treatment was 9 days[interquartile range(IQR):2.5-11.0 days]and 16 days(IQR:15.0-19.0 days)in the SCT and LCT groups,respectively,with a statistically significant difference(P<0.05).No significant differences were observed in 30-day mortality,cholangitis recurrence,or reinfection with the same organisms within 3 months.However,the length of hospital stay was shorter in the SCT group(median:12.0 days vs 14.0 days,P=0.092).CONCLUSION For acute cholangitis complicated by GPC bacteremia,shorter antimicrobial treatment may be a viable option following appropriate biliary drainage.Further studies with larger sample sizes are warranted.展开更多
Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts,leading to cholestasis and,in advanced stages,cirrhosis.While it primarily affects middle-aged wo...Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts,leading to cholestasis and,in advanced stages,cirrhosis.While it primarily affects middle-aged women,recent data indicate a rising incidence in men.The interplay between genetic susceptibility,environmental exposures,and gut microbiome alterations is thought to drive disease onset.Diagnosis relies on persistent cholestatic enzyme elevation,diseasespecific autoantibodies,and,in select cases,liver biopsy.Ursodeoxycholic acid remains the cornerstone of treatment,but many patients show an incomplete response.The recent withdrawal of obeticholic acid from the market,due to insufficient evidence of long-term benefit,has highlighted the urgent need for effective second-line therapies.Agonists of peroxisome proliferator-activated receptors,such as elafibranor and seladelpar,have demonstrated promising biochemical improvements and may reshape the therapeutic landscape.Future research is focused on refining risk assessment,optimizing treatment combinations,and addressing symptoms such as fatigue and pruritus to enhance patient well-being.A shift toward early intervention and personalized treatment strategies may further improve long-term outcomes in primary biliary cholangitis.展开更多
In this article,we discussed the article by Sohail et al,published in a recent issue of the World Journal of Gastrointestinal Endoscopy.This study highlights the benefits of performing cholecystectomy(CCY)during the s...In this article,we discussed the article by Sohail et al,published in a recent issue of the World Journal of Gastrointestinal Endoscopy.This study highlights the benefits of performing cholecystectomy(CCY)during the same hospitalization for patients with acute cholangitis(AC)associated with gallstones.Specifically,same-admission CCY is associated with significantly lower 30-day readmission rates compared with interval CCY.Furthermore,it has been associated with reduced mortality rates and reduced recurrence of biliary symptoms.Despite these advantages,the procedure is chosen in only a minority of eligible patients.This gap between evidence and practice highlights the need for updated clinical guidelines and further research to optimize the timing of CCY in the management of AC.展开更多
Background:Acute cholangitis is an infection due to the bile duct obstruction.Despite progress in treat-ment,acute cholangitis remains potentially fatal.Early diagnosis and treatment improve the patient out-comes.The ...Background:Acute cholangitis is an infection due to the bile duct obstruction.Despite progress in treat-ment,acute cholangitis remains potentially fatal.Early diagnosis and treatment improve the patient out-comes.The present study aimed to identify clinical and biological factors at admission associated with 30-day mortality in acute cholangitis,to build an efficient prognostic score based on these parameters and to study the performances of this new score.Methods:We enrolled all adult patients consecutively hospitalized for acute cholangitis between January 2017 and December 2021.We developed a score system named ProChol using variables significantly asso-ciated with 30-day mortality in multivariate logistic analysis and simplified this system(named sProChol)based on a simple points-based approach.Results:In total,528 patients were included,with an average age of 77±13 years,a male predominance(54.2%)and a majority of lithiasis etiology(66.5%).Mortality in 30 days was 11.9%.In multivariate logis-tic analysis,tumor etiology[adjusted odds ratio(aOR)=15.43,95%confidence interval(CI):5.90-40.40],stent obstruction(aOR=5.12,95%CI:2.02-12.99),hypoalbuminemia(aOR=3.50,95%CI:1.25-9.81),renal failure(aOR=6.51,95%CI:2.62-16.18),oxygen therapy(aOR=4.63,95%CI:1.02-20.92)and cu-rative anticoagulation(aOR=2.60,95%CI:1.23-5.52)were independently associated with the 30-day mortality while fever was a protective factor(aOR=0.37,95%CI:0.16-0.84).ProChol score using these 7 parameters and sProChol using the 3 robust factors(etiology,renal failure and anticoagulation)presented respectively an area under receiver operating characteristic(ROC)curves(AUC)of 0.81 and 0.77,higher than Tokyo(AUC=0.72)and Gravito-Soares et al.score(AUC=0.71).Patients with sProChol≥4 had a significantly higher risk of transfer to intensive care unit(13.3%vs.5.1%;P<0.001)and longer length of stay(P=0.0006).Conclusions:ProChol and sProChol constructed from simple clinico-biological parameters at admission,present interesting performances in predicting the 30-day mortality in acute cholangitis.展开更多
BACKGROUND Patients with concurrent acute biliary pancreatitis(ABP)and acute cholangitis(AC)may experience exacerbated clinical consequences due to bile duct stones.However,studies exploring this topic remain limited....BACKGROUND Patients with concurrent acute biliary pancreatitis(ABP)and acute cholangitis(AC)may experience exacerbated clinical consequences due to bile duct stones.However,studies exploring this topic remain limited.AIM To compare the clinical presentation and outcomes of patients experiencing AC with and without ABP.METHODS This single-center retrospective cohort study included 358 patients with AC who underwent endoscopic retrograde cholangiopancreatography(ERCP)between January 2016 and December 2017.Patients were divided into two groups:AC with ABP(n=90)and AC without ABP(n=268).Clinical characteristics,laboratory data,ERCP results,primary study outcome[intensive care unit(ICU)admission],and secondary outcomes including 30-day mortality,length of hospital stay,and 30-day readmission rate were analyzed and compared.RESULTS All patients in the AC with ABP group had interstitial pancreatitis.The AC with ABP group had significantly higher white cell count(WBC)counts(13.1×10^(3)/μL vs 10.4×10^(3)/μL,P=0.007)and more abnormal WBC results(61.1%vs 42.3%,P=0.015).Liver biochemical tests,AC severity,ERCP success,adverse events,ICU admissions,30-day mortality,hospital stay,and readmission rates did not differ significantly between the two groups.Univariate analysis showed no significant link between concurrent ABP and ICU admission,although significance was marginal in moderate/severe ABP cases(P=0.051).In the multivariate analysis,age(P=0.035)and cardiovascular dysfunction(P<0.001)were independently associated with length of ICU stay.CONCLUSION Concurrent interstitial ABP and AC did not significantly affect outcomes.Age and cardiovascular dysfunction were stronger predictors of ICU admission and should guide clinical monitoring and management.展开更多
Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing ...Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing body of evidence suggests that nanoparticles encapsulating rapamycin(ImmTOR)can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases.In a recent study,Yang et al investigated the therapeutic effects of ImmTOR in a mouse model of PBC.ImmTOR treatment reduced the expression and number of CD4+T cells,CD8+T cells,and B cells isolated from the liver and spleen,improved liver inflammation and enzyme levels,and was associated with a concomitant decrease in anti-mitochondrial antibody levels.In this editorial,we highlight the significance of these findings,focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels,ultimately improving liver pa-thology,through pathways such as mammalian target of rapamycin inhibition and autophagy restoration.We also offer a perspective on future research di-rections for PBC in both animal models and in vitro studies.展开更多
BACKGROUND Situs inversus viscerum(SIV)is a rare autosomal recessive genetic disorder characterized a complete mirror-image organ reversal in the thoracic and abdo-minal cavities.Its low incidence presents considerabl...BACKGROUND Situs inversus viscerum(SIV)is a rare autosomal recessive genetic disorder characterized a complete mirror-image organ reversal in the thoracic and abdo-minal cavities.Its low incidence presents considerable challenges in clinical dia-gnosis and treatment,especially concerning gastrointestinal endoscopic proce-dures.CASE SUMMARY Herein,we report a case of an 80-year-old male with choledocholithiasis and acute obstructive empyematous cholangitis.Imaging revealed total visceral inversion in the patient.Endoscopic retrograde cholangiopancreatography(ERCP)was successfully performed to remove the stones,resulting to substantial relief of clinical symptoms and gradual improvement of the patient’s condition,leading to successful recovery and discharge.CONCLUSION Therapeutic ERCP is a safe and effective surgical option for patients with SIV.The main focus for successful ERCP in patients with SIV includes positioning adju-stments during the surgical process and using the dual-guidewire technique for biliary cannulation.展开更多
BACKGROUND Primary sclerosing cholangitis(PSC)is a long-term liver condition defined by the inflammation and scarring of the bile ducts,resulting in complications such as liver cirrhosis,portal hypertension,and cholan...BACKGROUND Primary sclerosing cholangitis(PSC)is a long-term liver condition defined by the inflammation and scarring of the bile ducts,resulting in complications such as liver cirrhosis,portal hypertension,and cholangiocarcinoma.Although PSC predominantly affects adults,the incidence in pediatric patients is rising.For individuals in the advanced stages of liver disease,liver transplantation(LT)is the sole curative treatment option.However,the recurrence of PSC in the transplanted liver,known as recurrent PSC(rPSC),remains a significant concern.AIM To identify the potential risk factors for the recurrence of PSC in pediatric patients after undergoing LT.METHODS A literature search was carried out across databases,including PubMed,Embase,Cochrane Library,and Scopus,covering studies published from 1990 through 2024.The Newcastle-Ottawa scale was utilized to assess the quality of the selected studies.Statistical analyses were conducted using RevMan 5.3 software,where the risk of recurrence was quantified using hazard ratios(HR)with 95%CI.RESULTS A total of nine reports with 2524 pediatric patients with PSC were included in this analysis.The findings revealed several important risk factors connected to the rPSC in pediatric patients who had received a liver transplant,including concurrent inflammatory bowel disease(IBD),elevated liver enzyme levels,and the presence of PSCautoimmune hepatitis(AIH)overlap syndrome(all P<0.05).No statistically significant association was found between acute allograft rejection,Epstein-Barr virus infection,and the risk of rPSC recurrence in the pediatric liver transplant recipients.CONCLUSION The present systematic review and meta-analysis have identified various risk factors associated with the recurrence of PSC in pediatric patients who underwent LT,including IBD,elevated liver enzyme levels,and PSC-AIH overlap syndrome.展开更多
BACKGROUND Ursodeoxycholic acid(UDCA)is the first-line therapeutic agent for primary biliary cholangitis(PBC).However,a subset of patients exhibit a suboptimal response to UDCA,and reliable predictive biomarkers remai...BACKGROUND Ursodeoxycholic acid(UDCA)is the first-line therapeutic agent for primary biliary cholangitis(PBC).However,a subset of patients exhibit a suboptimal response to UDCA,and reliable predictive biomarkers remain elusive.Studies have implicated plasma microRNAs(miRNAs)in the pathophysiological pro-gression of PBC,with certain miRNAs demonstrating potential as diagnostic and disease progression biomarkers.However,biomarkers capable of predicting the therapeutic efficacy of UDCA have not yet been identified.AIM To investigate differentially expressed miRNAs in PBC patients with divergent UDCA treatment responses and to explore potential biomarkers that predict treatment response in PBC.METHODS Plasma samples from treatment-naive PBC patients receiving≥1 year of standard UDCA treatment were collected.Efficacy was evaluated using the Paris I criteria.Patient samples were divided into discovery group(n=10)and validation group(n=30),with further stratification of patients into drug-resistant and drug-sensitive(DS)cohorts.Next-generation sequencing and quantitative real-time polymerase chain reaction were used to screen,functionally analyze,and validate the pre-treatment miRNA profiles of the treatment groups.RESULTS Forty-nine miRNAs were differentially expressed between the two groups before UDCA treatment(N=40).MiR-22-5p and miR-126-3p were highly expressed in the DS group before treatment(P<0.001),whereas miR-7706 exhibited a low expression(P=0.017).Post-treatment,miR-126-3p maintained low expression in the drug-resistant group(P=0.003),but showed elevated levels in the DS group(P<0.001).Logistic regression analysis identified miR-126-3p expression(odds ratio=34.32,95%confidence interval:1.95-605.40,P=0.016)as a significant factor influencing UDCA treatment response,while miR-22-5p(P=0.990)and miR-7706(P=0.157)showed no significant association.MiR-126-3p levels were negatively correlated with total bilirubin(r=-0.356,P=0.005)and immuno-globulin G levels(r=-0.311,P=0.015).The area under the receiver operating characteristic curve was 0.891(P=0.0003,95%confidence interval:0.772-1.000)with a sensitivity of 82.4%and a specificity of 84.6%.CONCLUSION Plasma miRNA expression profiles are heterogenous in patients with PBC with differential responses to UDCA therapy.MiR-126-3p demonstrates predictive potential for a suboptimal response to UDCA in patients with PBC.展开更多
BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identi...BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment.METHODS Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls.Immunohistochemistry was performed to validate key genes in liver tissues of the participants.Logistic regression was employed to evaluate prognostic risk factors,receiver operating characteristic curves were used to assess predictive performance,and correlations between key genes and clinicopathological characteristics were analyzed.RESULTS By bioinformatic analysis,13 genes primarily associated with the progression of PBC were identified,and tumor necrosis factor alpha-induced protein 3(TNFAIP3)was selected for further investigation.Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry(P<0.0001).Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients(P<0.05).The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704,respectively,while their combination showed a significantly higher area under the curve of 0.848.The expression of TNFAIP3 was also correlated with age,albumin,total bilirubin,alkaline phosphatase and splenomegaly(P<0.05).CONCLUSION TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC.TNFAIP3 may be a potential biomarker or therapeutic target for PBC.These findings offer new insights into the pathogenesis of PBC.展开更多
This article relates to the discussion of a recent study published by Wohl et al.Primary sclerosing cholangitis(PSC)is a chronic inflammatory liver disease that affects the intra-and extrahepatic bile ducts and is str...This article relates to the discussion of a recent study published by Wohl et al.Primary sclerosing cholangitis(PSC)is a chronic inflammatory liver disease that affects the intra-and extrahepatic bile ducts and is strongly associated with ulcerative colitis(UC).Endoscopic evaluation of UC is feasible and reliable in routine clinical practice,and the Mayo endoscopic subscore(MES)is one of the most commonly used endoscopic evaluation measures for UC.Patients with PSCUC are at higher risk of developing cancer and biliary tract cancer.Endoscopic scoring alone appears unreliable,and histopathological evaluation is essential to accurately assess and make effective therapeutic decisions for PSC-UC.Therefore,we aimed to discuss the accuracy of MES in patients with UC and PSC-UC and to explore the consistency between MES and the Nancy histological index.展开更多
BACKGROUND There is insufficient evidence on the evaluation of liver fibrosis in Asian indivi-duals with primary biliary cholangitis(PBC)using vibration-controlled transient elastography(VCTE).AIM To assess advanced f...BACKGROUND There is insufficient evidence on the evaluation of liver fibrosis in Asian indivi-duals with primary biliary cholangitis(PBC)using vibration-controlled transient elastography(VCTE).AIM To assess advanced fibrosis(AF)using liver stiffness measurement(LSM)in Chinese patients with PBC.METHODS In total,277 Chinese patients diagnosed with PBC who underwent liver biopsy and VCTE were retrospectively included and categorized into the derivation and validation cohorts.The areas under the receiver operating characteristic curves(AUROCs)with 95%confidence intervals(CIs)were used to estimate the dia-gnostic accuracy of LSM for AF(Ludwig stage≥III).Multivariable analysis was performed using logistic regression.RESULTS In the derivation cohort,VCTE accurately detected patients with AF,achieving an AUROC of 0.93(95%CI:0.88-0.96).AF was independently predicted by LSM according to multivariable analysis.AF can be excluded and confirmed using LSM cutoffs of≤10.0 and>14.5 kPa,respectively,with a sensitivity of 0.91,negative predictive value of 0.93,specificity of 0.96,positive predictive value of 0.92,and an error rate of 7.5%.The accuracy of these values was validated in an independent cohort,achieving an AUROC of 0.97(95%CI:0.90-0.99)for AF with a sensitivity of 0.89,negative predictive value of 0.88,specificity of 0.95,positive predictive value of 0.94,and error rate of 9.0%.Compared with serum fibrosis markers,the AUROC of LSM was significantly higher in both the derivation and validation cohorts.CONCLUSION VCTE has a high accuracy for assessing AF in Chinese patients with PBC in a real-world setting.展开更多
BACKGROUND Steroid-refractory immune-related cholangitis,characterized by biliary obstru-ction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis afte...BACKGROUND Steroid-refractory immune-related cholangitis,characterized by biliary obstru-ction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis after ICI administration,the the-rapeutic importance of local relief of obstruction has not been reported.CASE SUMMARY A 60-year-old female patient with biliary tract carcinoma and peritoneal metastasis developed elevated liver enzymes following four cycles of combined therapy with anti-PD-1(Pembrolizumab)and a tyrosine kinase inhibitor.Magne-tic resonance cholangiopancreatography indicated a thickening of the upper bile duct and pancreatic sections with narrow lumens.Digital peroral cholangioscopy revealed several erosions and surface vessel tortuosities coating the common bile duct.Endoscopic ultrasound revealed disruption of the middle lumen segment,with poorly defined wall structures.Endoscopic retrograde cholangiopancreato-graphy(ERCP)demonstrated mucosal irregularities with tortuous surface vessels along the common bile duct.Angiographic imaging revealed irregular defects in the middle and lower common bile duct segments,while the proximal duct exhibited multifocal stenosis alternating with dilatation.Biopsy samples obtained via ERCP from the elevated mucosal lesions showed dense epithelial inflam-matory cell infiltration,consistent with immune-related cholangitis.Both biliary enzymes can be decreased to a certain degree by corticosteroid and ursodeoxy-cholic acid therapy but are difficult to reduce to normal levels.Liver function normalized,and symptoms improved after local treatment for cholestasis(stent implantation).CONCLUSION Stent placement offers prompt alleviation of cholestasis and constitutes an effective therapeutic strategy for managing immune-related cholangitis.展开更多
Primary biliary cholangitis(PBC)is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction,leading to fibrosis,cirrhosis,and eventual liver failure.Over the past two decades,s...Primary biliary cholangitis(PBC)is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction,leading to fibrosis,cirrhosis,and eventual liver failure.Over the past two decades,significant advancements have paved the way for novel therapeutic strategies.Ursodeoxycholic acid(UDCA)has been the cornerstone of PBC management,improving survival and delaying disease progression in most patients.However,up to 40%of patients demonstrate an inadequate response to UDCA,necessitating additional treatment options.Obeticholic acid(OCA),a farnesoid X receptor agonist,has emerged as a second-line therapy,showing efficacy in reducing alkaline phosphatase levels and improving liver biochemistry.Beyond UDCA and OCA,a new wave of therapeutic agents are reshaping the PBC landscape.These include fibrates,peroxisome proliferator-activated receptor agonists and novel immunomodulatory drugs aimed at reducing autoimmune-mediated liver injury.Bile acid transport inhibitors,anti-fibrotic agents,and gut microbiome-targeted therapies are also under investigation,offering hope for personalized treatment approaches.This review highlights the evolution of PBC therapy,emphasizing the unmet needs of patients with refractory disease and the potential of emerging therapies to improve outcomes.As the therapeutic landscape continues to expand,optimizing treatment strategies through precision medicine holds the promise of transforming the management of PBC.展开更多
BACKGROUND The diagnosis of primary biliary cholangitis(PBC)remains challenging,particularly in cases where anti-mitochondrial antibody(AMA),anti-mitochondrial E2 subunit antibody(AMA-M2),anti-glycoprotein 210(anti-gp...BACKGROUND The diagnosis of primary biliary cholangitis(PBC)remains challenging,particularly in cases where anti-mitochondrial antibody(AMA),anti-mitochondrial E2 subunit antibody(AMA-M2),anti-glycoprotein 210(anti-gp210),and anti-speckled protein 100(anti-Sp100)are all negative.In such instances,the condition is often confirmed through a liver needle biopsy.AIM To identify additional plasma biomarkers for non-invasive diagnostic methods of PBC.METHODS We utilized the Sengenics KREX^(TM)immunome protein array to identify potential biomarkers for the diagnosis of PBC.Subsequently,we validated the predictive capability of the RPL30 antibody through an ELISA and retrospectively analyzed its association with the clinical features of 17 autoantibody-negative PBC cases and 45 autoantibody-positive PBC cases.RESULTS In our study we observed that RPL30 demonstrated the highest fold-change difference in PBC,with a penetrance frequency of 40%and a penetrance fold change of 38.30147.The analysis of anti-RPL30 optical density values between patients with AMA/AMA-M2/anti-gp210/anti-Sp100-negative PBC(autoantibody-negative PBC)and healthy controls using a receiver operating characteristic curve yielded an area under the curve of 0.853.This analysis established an optimal cutoff value of 0.0708,achieving 100%specificity and 75%sensitivity.The combination of anti-RPL30 and other autoantibodies elevated the diagnosis rate of PBC from 61.29%to 79.00%(P=0.0489).Anti-RPL30 demonstrated a high positive rate in antibody-negative PBC cases,including AMA/AMAM2/anti-gp210/anti-Sp100-negative cases.Correlation analysis of anti-RPL30 optical density values with clinical data from patients with PBC revealed a positive association with both the international normalized ratio(P=0.008)and the Model for End-Stage Liver Disease score(P=0.003).CONCLUSION Our study highlighted the potential of anti-RPL30 as a promising biomarker for diagnosing PBC,particularly in autoantibody-negative cases.展开更多
The concurrence of primary sclerosing cholangitis(PSC)and inflammatory bowel disease(IBD)presents a therapeutic challenge,often necessitating liver transplantation in severe cases.Paeoniflorin(PAE),known for its immun...The concurrence of primary sclerosing cholangitis(PSC)and inflammatory bowel disease(IBD)presents a therapeutic challenge,often necessitating liver transplantation in severe cases.Paeoniflorin(PAE),known for its immunomodulatory and anti-inflammatory properties but with very high-water solubility and low permeability,is formulated into a paeoniflorin/phospholipid complex microemulsion(PAE-ME)to enhance its delivery in this study.It demonstrated the PAE-ME's macrophage-regulating ability to repolarize the pro-inflammatory M1 subtype to the anti-inflammatory M2 type and reduce inflammatory cytokine release.In a PSC-IBD mouse model,PAE-ME alleviated the symptoms and regulated bile acid balance.Given the close connection and crosstalk between the liver and intestine,PAE-ME yielded a synergistic therapeutic effect on both the liver and intestinal lesions.These findings suggest a promising translational approach for complex comorbidities by acting on the liver-gut axis.展开更多
BACKGROUND T helper 17(Th17)cell infiltration and interleukin(IL)-17 secretion in intrahepatic small bile ducts is a critical driver of immune-mediated injury in primary biliary cholangitis(PBC).IL-6 is an essential u...BACKGROUND T helper 17(Th17)cell infiltration and interleukin(IL)-17 secretion in intrahepatic small bile ducts is a critical driver of immune-mediated injury in primary biliary cholangitis(PBC).IL-6 is an essential upstream activator of Th17 cells.Basophilderived IL-6 promotes the differentiation of CD4+T cells and Th1 cells into Th17 cells,thereby regulating their immunological functions.AIM To investigate the activation status and cytokine expression of basophils in PBC,elucidating potential mechanisms through which basophils contribute to its pathogenesis.METHODS This single-center retrospective case-control study conducted at Guangdong Medical University Affiliated Hospital(China)between September 2019 and August 2024 enrolled 65 consecutive treatment-naïve patients with PBC(PBC group),65 age-and sex-matched patients with chronic hepatitis B(CHB group),and 65 healthy controls(Normal group).Fourteen participants per group(subgroup)were randomly selected for flow cytometry analysis of basophil proportion,activation markers(CD203c and CD62 L mean fluorescence intensity),IL-6-positive basophils(IL-6+basophils as a percentage of total basophils),and IL-17-positive T lymphocytes(CD3+CD4+IL-17+cells)proportion among T cells.Data were analyzed using Kruskal-Wallis and χ^(2) tests as appropriate.RESULTS Routine blood tests revealed significantly higher basophil counts and proportions in the PBC group compared to the CHB and Normal groups(P<0.001 for both comparisons),with no significant differences between the CHB and Normal groups(P=0.201).Flow cytometry revealed a higher basophil proportion in the PBC subgroup compared to the CHB(P=0.011)and Normal subgroups(P<0.001).The mean fluorescence intensity of CD203c on basophil surfaces was elevated in the PBC subgroup compared to the CHB(P=0.032)and Normal subgroups(P=0.039).The proportion of IL-6+basophils was significantly higher in the PBC subgroup than in the CHB(P<0.01)and Normal subgroups(P<0.001).Similarly,the Th17 cell proportion was markedly elevated in the PBC compared to the CHB(P<0.001)and Normal subgroups(P<0.001).CONCLUSION Patients with PBC have increased peripheral basophil counts with enhanced activation.Activated basophils have increased IL-6 expression,which may indirectly induce Th17 cell proliferation and contribute to PBC pathogenesis.展开更多
文摘Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.
文摘To the Editor:Acute cholangitis,also known as ascending cholangitis,is a po-tentially life-threatening condition resulting from the infection and obstruction of the biliary tract[1].Choledocholithiasis,which in-volves stones in the common bile duct,is the most frequent cause of such infections,leading to partial or complete blockage of the biliary system[2].During acute episodes,patients may present with abdominal pain,high fever,and jaundice,known as Charcot’s triad,and in severe cases,patients may also exhibit signs of shock and depression[3].An episode of cholangitis can be fatal,and if the underlying obstruction is not addressed,the condition may recur,potentially leading to hepatic abscesses or biliary cirrhosis.Other etiologies of cholangitis include benign biliary strictures,bil-iary malignancies,congenital factors,postoperative complications,inflammatory conditions,and rare causes such as pancreatitis,par-asitic invasion of the biliary tract,external compression,thrombo-sis,and iatrogenic factors.Acute cholecystitis due to the migration of Hem-o-lok clips postoperation is rare.Herein we reported a case of acute cholangitis caused by the migration of surgical Hem-o-lok clips into the bile duct six years after laparoscopic left hemihepa-tectomy.
基金Supported by Cultivation Project of Hebei Natural Science Foundation-Precision Medicine Joint Fund,No.H2021206239.
文摘BACKGROUND Primary biliary cholangitis(PBC)is a chronic autoimmune-mediated cholestatic liver disease.Nanoparticles encapsulating rapamycin(ImmTOR)suppress adaptive immune responses and induce the hepatic tolerogenic immune response.AIM To investigate the effects of ImmTOR in PBC mouse models.METHODS PBC models were induced in C57BL/6 mice by two immunizations of 2-octynoic acid-coupled bovine serum albumin at two-week intervals,and polycytidylic acid every three days.The PBC mouse models were separated into the treatment group and the control group.The levels of alkaline phosphatase(ALP)and alanine aminotransferase in the mice were detected using an automatic biochemical analyzer.Liver and spleen mononuclear cells were analyzed by flow cytometry,and serum anti-mitochondrial antibodies(AMA)and the related cytokines were analyzed by enzyme-linked immunosorbent assay.Liver histopathology was examined by hematoxylin and eosin staining and scored.RESULTS After treatment with ImmTOR,the ALP level was significantly decreased(189.60 U/L±27.25 U/L vs 156.00 U/L±17.21 U/L,P<0.05),the level of AMA was reduced(1.28 ng/mL±0.27 ng/mL vs 0.56 ng/mL±0.07 ng/mL,P<0.001)and the expression levels of interferon gamma and tumor necrosis factorαwere significantly decreased(48.29 pg/mL±10.84 pg/mL vs 25.01 pg/mL±1.49 pg/mL,P<0.0001)and(84.24 pg/mL±23.47 pg/mL vs 40.66 pg/mL±14.65 pg/mL,P<0.001).The CD4+T lymphocytes,CD8+T lymphocytes and B lymphocytes in the liver were significantly reduced,with statistically significant differences(24.21%±6.55%vs 15.98%±3.03%,P<0.05;9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The expression of CD8+T lymphocytes and B lymphocytes in the ImmTOR treatment group also decreased(9.09%±1.91%vs 5.49%±1.00%,P<0.001;80.51%±2.96%vs 75.31%±4.34%,P<0.05).The liver pathology of PBC mice in the treatment group showed reduced inflammation and a decreased total pathology score,and the difference in the scores was statistically significant(4.50±2.88 vs 1.75±1.28,P<0.05).CONCLUSION ImmTOR can improve biochemistry and pathology of liver obvious by inhibiting the expression of CD8+T cells and B cells,and reducing the titer of AMA.
文摘BACKGROUND The optimal duration of antimicrobial treatment for acute cholangitis complicated by gram-positive coccus(GPC)bacteremia remains unclear.The Tokyo Guidelines 2018 recommended 14 days of antimicrobial treatment following adequate source control measures;however,evidence supporting this recommendation is limited,and deviations from real-world practice are often observed.AIM To evaluate the efficacy and safety of shorter antimicrobial treatments for acute cholangitis complicated by GPC bacteremia.METHODS Adult patients with acute cholangitis complicated by GPC bacteremia who underwent endoscopic retrograde cholangiopancreatography between July 2003 and December 2023 were included.Patients were categorized into two groups based on the duration of effective antimicrobial treatment:(1)Short-course treatment(SCT)(<14 days);and(2)Long-course treatment(LCT)(≥14 days).The outcomes assessed included mortality,recurrence,reinfection with the same organism related to the cholangitis,and length of hospital stay.RESULTS A total of 44 patients were included in the study:(1)19 patients in the SCT group;and(2)25 patients in the LCT group.The median duration of antimicrobial treatment was 9 days[interquartile range(IQR):2.5-11.0 days]and 16 days(IQR:15.0-19.0 days)in the SCT and LCT groups,respectively,with a statistically significant difference(P<0.05).No significant differences were observed in 30-day mortality,cholangitis recurrence,or reinfection with the same organisms within 3 months.However,the length of hospital stay was shorter in the SCT group(median:12.0 days vs 14.0 days,P=0.092).CONCLUSION For acute cholangitis complicated by GPC bacteremia,shorter antimicrobial treatment may be a viable option following appropriate biliary drainage.Further studies with larger sample sizes are warranted.
文摘Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts,leading to cholestasis and,in advanced stages,cirrhosis.While it primarily affects middle-aged women,recent data indicate a rising incidence in men.The interplay between genetic susceptibility,environmental exposures,and gut microbiome alterations is thought to drive disease onset.Diagnosis relies on persistent cholestatic enzyme elevation,diseasespecific autoantibodies,and,in select cases,liver biopsy.Ursodeoxycholic acid remains the cornerstone of treatment,but many patients show an incomplete response.The recent withdrawal of obeticholic acid from the market,due to insufficient evidence of long-term benefit,has highlighted the urgent need for effective second-line therapies.Agonists of peroxisome proliferator-activated receptors,such as elafibranor and seladelpar,have demonstrated promising biochemical improvements and may reshape the therapeutic landscape.Future research is focused on refining risk assessment,optimizing treatment combinations,and addressing symptoms such as fatigue and pruritus to enhance patient well-being.A shift toward early intervention and personalized treatment strategies may further improve long-term outcomes in primary biliary cholangitis.
文摘In this article,we discussed the article by Sohail et al,published in a recent issue of the World Journal of Gastrointestinal Endoscopy.This study highlights the benefits of performing cholecystectomy(CCY)during the same hospitalization for patients with acute cholangitis(AC)associated with gallstones.Specifically,same-admission CCY is associated with significantly lower 30-day readmission rates compared with interval CCY.Furthermore,it has been associated with reduced mortality rates and reduced recurrence of biliary symptoms.Despite these advantages,the procedure is chosen in only a minority of eligible patients.This gap between evidence and practice highlights the need for updated clinical guidelines and further research to optimize the timing of CCY in the management of AC.
文摘Background:Acute cholangitis is an infection due to the bile duct obstruction.Despite progress in treat-ment,acute cholangitis remains potentially fatal.Early diagnosis and treatment improve the patient out-comes.The present study aimed to identify clinical and biological factors at admission associated with 30-day mortality in acute cholangitis,to build an efficient prognostic score based on these parameters and to study the performances of this new score.Methods:We enrolled all adult patients consecutively hospitalized for acute cholangitis between January 2017 and December 2021.We developed a score system named ProChol using variables significantly asso-ciated with 30-day mortality in multivariate logistic analysis and simplified this system(named sProChol)based on a simple points-based approach.Results:In total,528 patients were included,with an average age of 77±13 years,a male predominance(54.2%)and a majority of lithiasis etiology(66.5%).Mortality in 30 days was 11.9%.In multivariate logis-tic analysis,tumor etiology[adjusted odds ratio(aOR)=15.43,95%confidence interval(CI):5.90-40.40],stent obstruction(aOR=5.12,95%CI:2.02-12.99),hypoalbuminemia(aOR=3.50,95%CI:1.25-9.81),renal failure(aOR=6.51,95%CI:2.62-16.18),oxygen therapy(aOR=4.63,95%CI:1.02-20.92)and cu-rative anticoagulation(aOR=2.60,95%CI:1.23-5.52)were independently associated with the 30-day mortality while fever was a protective factor(aOR=0.37,95%CI:0.16-0.84).ProChol score using these 7 parameters and sProChol using the 3 robust factors(etiology,renal failure and anticoagulation)presented respectively an area under receiver operating characteristic(ROC)curves(AUC)of 0.81 and 0.77,higher than Tokyo(AUC=0.72)and Gravito-Soares et al.score(AUC=0.71).Patients with sProChol≥4 had a significantly higher risk of transfer to intensive care unit(13.3%vs.5.1%;P<0.001)and longer length of stay(P=0.0006).Conclusions:ProChol and sProChol constructed from simple clinico-biological parameters at admission,present interesting performances in predicting the 30-day mortality in acute cholangitis.
文摘BACKGROUND Patients with concurrent acute biliary pancreatitis(ABP)and acute cholangitis(AC)may experience exacerbated clinical consequences due to bile duct stones.However,studies exploring this topic remain limited.AIM To compare the clinical presentation and outcomes of patients experiencing AC with and without ABP.METHODS This single-center retrospective cohort study included 358 patients with AC who underwent endoscopic retrograde cholangiopancreatography(ERCP)between January 2016 and December 2017.Patients were divided into two groups:AC with ABP(n=90)and AC without ABP(n=268).Clinical characteristics,laboratory data,ERCP results,primary study outcome[intensive care unit(ICU)admission],and secondary outcomes including 30-day mortality,length of hospital stay,and 30-day readmission rate were analyzed and compared.RESULTS All patients in the AC with ABP group had interstitial pancreatitis.The AC with ABP group had significantly higher white cell count(WBC)counts(13.1×10^(3)/μL vs 10.4×10^(3)/μL,P=0.007)and more abnormal WBC results(61.1%vs 42.3%,P=0.015).Liver biochemical tests,AC severity,ERCP success,adverse events,ICU admissions,30-day mortality,hospital stay,and readmission rates did not differ significantly between the two groups.Univariate analysis showed no significant link between concurrent ABP and ICU admission,although significance was marginal in moderate/severe ABP cases(P=0.051).In the multivariate analysis,age(P=0.035)and cardiovascular dysfunction(P<0.001)were independently associated with length of ICU stay.CONCLUSION Concurrent interstitial ABP and AC did not significantly affect outcomes.Age and cardiovascular dysfunction were stronger predictors of ICU admission and should guide clinical monitoring and management.
文摘Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing body of evidence suggests that nanoparticles encapsulating rapamycin(ImmTOR)can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases.In a recent study,Yang et al investigated the therapeutic effects of ImmTOR in a mouse model of PBC.ImmTOR treatment reduced the expression and number of CD4+T cells,CD8+T cells,and B cells isolated from the liver and spleen,improved liver inflammation and enzyme levels,and was associated with a concomitant decrease in anti-mitochondrial antibody levels.In this editorial,we highlight the significance of these findings,focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels,ultimately improving liver pa-thology,through pathways such as mammalian target of rapamycin inhibition and autophagy restoration.We also offer a perspective on future research di-rections for PBC in both animal models and in vitro studies.
文摘BACKGROUND Situs inversus viscerum(SIV)is a rare autosomal recessive genetic disorder characterized a complete mirror-image organ reversal in the thoracic and abdo-minal cavities.Its low incidence presents considerable challenges in clinical dia-gnosis and treatment,especially concerning gastrointestinal endoscopic proce-dures.CASE SUMMARY Herein,we report a case of an 80-year-old male with choledocholithiasis and acute obstructive empyematous cholangitis.Imaging revealed total visceral inversion in the patient.Endoscopic retrograde cholangiopancreatography(ERCP)was successfully performed to remove the stones,resulting to substantial relief of clinical symptoms and gradual improvement of the patient’s condition,leading to successful recovery and discharge.CONCLUSION Therapeutic ERCP is a safe and effective surgical option for patients with SIV.The main focus for successful ERCP in patients with SIV includes positioning adju-stments during the surgical process and using the dual-guidewire technique for biliary cannulation.
文摘BACKGROUND Primary sclerosing cholangitis(PSC)is a long-term liver condition defined by the inflammation and scarring of the bile ducts,resulting in complications such as liver cirrhosis,portal hypertension,and cholangiocarcinoma.Although PSC predominantly affects adults,the incidence in pediatric patients is rising.For individuals in the advanced stages of liver disease,liver transplantation(LT)is the sole curative treatment option.However,the recurrence of PSC in the transplanted liver,known as recurrent PSC(rPSC),remains a significant concern.AIM To identify the potential risk factors for the recurrence of PSC in pediatric patients after undergoing LT.METHODS A literature search was carried out across databases,including PubMed,Embase,Cochrane Library,and Scopus,covering studies published from 1990 through 2024.The Newcastle-Ottawa scale was utilized to assess the quality of the selected studies.Statistical analyses were conducted using RevMan 5.3 software,where the risk of recurrence was quantified using hazard ratios(HR)with 95%CI.RESULTS A total of nine reports with 2524 pediatric patients with PSC were included in this analysis.The findings revealed several important risk factors connected to the rPSC in pediatric patients who had received a liver transplant,including concurrent inflammatory bowel disease(IBD),elevated liver enzyme levels,and the presence of PSCautoimmune hepatitis(AIH)overlap syndrome(all P<0.05).No statistically significant association was found between acute allograft rejection,Epstein-Barr virus infection,and the risk of rPSC recurrence in the pediatric liver transplant recipients.CONCLUSION The present systematic review and meta-analysis have identified various risk factors associated with the recurrence of PSC in pediatric patients who underwent LT,including IBD,elevated liver enzyme levels,and PSC-AIH overlap syndrome.
基金Supported by the National Key Research and Development Program of China,No.2019YFC0840704Beijing Municipal Science and Technology Program,No.Z201100005520047.
文摘BACKGROUND Ursodeoxycholic acid(UDCA)is the first-line therapeutic agent for primary biliary cholangitis(PBC).However,a subset of patients exhibit a suboptimal response to UDCA,and reliable predictive biomarkers remain elusive.Studies have implicated plasma microRNAs(miRNAs)in the pathophysiological pro-gression of PBC,with certain miRNAs demonstrating potential as diagnostic and disease progression biomarkers.However,biomarkers capable of predicting the therapeutic efficacy of UDCA have not yet been identified.AIM To investigate differentially expressed miRNAs in PBC patients with divergent UDCA treatment responses and to explore potential biomarkers that predict treatment response in PBC.METHODS Plasma samples from treatment-naive PBC patients receiving≥1 year of standard UDCA treatment were collected.Efficacy was evaluated using the Paris I criteria.Patient samples were divided into discovery group(n=10)and validation group(n=30),with further stratification of patients into drug-resistant and drug-sensitive(DS)cohorts.Next-generation sequencing and quantitative real-time polymerase chain reaction were used to screen,functionally analyze,and validate the pre-treatment miRNA profiles of the treatment groups.RESULTS Forty-nine miRNAs were differentially expressed between the two groups before UDCA treatment(N=40).MiR-22-5p and miR-126-3p were highly expressed in the DS group before treatment(P<0.001),whereas miR-7706 exhibited a low expression(P=0.017).Post-treatment,miR-126-3p maintained low expression in the drug-resistant group(P=0.003),but showed elevated levels in the DS group(P<0.001).Logistic regression analysis identified miR-126-3p expression(odds ratio=34.32,95%confidence interval:1.95-605.40,P=0.016)as a significant factor influencing UDCA treatment response,while miR-22-5p(P=0.990)and miR-7706(P=0.157)showed no significant association.MiR-126-3p levels were negatively correlated with total bilirubin(r=-0.356,P=0.005)and immuno-globulin G levels(r=-0.311,P=0.015).The area under the receiver operating characteristic curve was 0.891(P=0.0003,95%confidence interval:0.772-1.000)with a sensitivity of 82.4%and a specificity of 84.6%.CONCLUSION Plasma miRNA expression profiles are heterogenous in patients with PBC with differential responses to UDCA therapy.MiR-126-3p demonstrates predictive potential for a suboptimal response to UDCA in patients with PBC.
基金Supported by the National Natural Science Foundation of China,No.81671600 and No.81241094Natural Science Foundation of Shandong Province,China,No.ZR2016HM13 and No.ZR2023MH066Qingdao Medical and Health Scientific Research Project,China,No.2024-WJKY160.
文摘BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment.METHODS Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls.Immunohistochemistry was performed to validate key genes in liver tissues of the participants.Logistic regression was employed to evaluate prognostic risk factors,receiver operating characteristic curves were used to assess predictive performance,and correlations between key genes and clinicopathological characteristics were analyzed.RESULTS By bioinformatic analysis,13 genes primarily associated with the progression of PBC were identified,and tumor necrosis factor alpha-induced protein 3(TNFAIP3)was selected for further investigation.Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry(P<0.0001).Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients(P<0.05).The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704,respectively,while their combination showed a significantly higher area under the curve of 0.848.The expression of TNFAIP3 was also correlated with age,albumin,total bilirubin,alkaline phosphatase and splenomegaly(P<0.05).CONCLUSION TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC.TNFAIP3 may be a potential biomarker or therapeutic target for PBC.These findings offer new insights into the pathogenesis of PBC.
文摘This article relates to the discussion of a recent study published by Wohl et al.Primary sclerosing cholangitis(PSC)is a chronic inflammatory liver disease that affects the intra-and extrahepatic bile ducts and is strongly associated with ulcerative colitis(UC).Endoscopic evaluation of UC is feasible and reliable in routine clinical practice,and the Mayo endoscopic subscore(MES)is one of the most commonly used endoscopic evaluation measures for UC.Patients with PSCUC are at higher risk of developing cancer and biliary tract cancer.Endoscopic scoring alone appears unreliable,and histopathological evaluation is essential to accurately assess and make effective therapeutic decisions for PSC-UC.Therefore,we aimed to discuss the accuracy of MES in patients with UC and PSC-UC and to explore the consistency between MES and the Nancy histological index.
基金Supported by the Capital’s Funds for Health Improvement and Research,No.CFH2024-1-2173State Administration of Traditional Chinese Medicine High-Level Key Disciplines Construction Project,No.zyyzdxk-2023005the Scientific Research Fund Project of Beijing Ditan Hospital,No.DTDR202403.
文摘BACKGROUND There is insufficient evidence on the evaluation of liver fibrosis in Asian indivi-duals with primary biliary cholangitis(PBC)using vibration-controlled transient elastography(VCTE).AIM To assess advanced fibrosis(AF)using liver stiffness measurement(LSM)in Chinese patients with PBC.METHODS In total,277 Chinese patients diagnosed with PBC who underwent liver biopsy and VCTE were retrospectively included and categorized into the derivation and validation cohorts.The areas under the receiver operating characteristic curves(AUROCs)with 95%confidence intervals(CIs)were used to estimate the dia-gnostic accuracy of LSM for AF(Ludwig stage≥III).Multivariable analysis was performed using logistic regression.RESULTS In the derivation cohort,VCTE accurately detected patients with AF,achieving an AUROC of 0.93(95%CI:0.88-0.96).AF was independently predicted by LSM according to multivariable analysis.AF can be excluded and confirmed using LSM cutoffs of≤10.0 and>14.5 kPa,respectively,with a sensitivity of 0.91,negative predictive value of 0.93,specificity of 0.96,positive predictive value of 0.92,and an error rate of 7.5%.The accuracy of these values was validated in an independent cohort,achieving an AUROC of 0.97(95%CI:0.90-0.99)for AF with a sensitivity of 0.89,negative predictive value of 0.88,specificity of 0.95,positive predictive value of 0.94,and error rate of 9.0%.Compared with serum fibrosis markers,the AUROC of LSM was significantly higher in both the derivation and validation cohorts.CONCLUSION VCTE has a high accuracy for assessing AF in Chinese patients with PBC in a real-world setting.
文摘BACKGROUND Steroid-refractory immune-related cholangitis,characterized by biliary obstru-ction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis after ICI administration,the the-rapeutic importance of local relief of obstruction has not been reported.CASE SUMMARY A 60-year-old female patient with biliary tract carcinoma and peritoneal metastasis developed elevated liver enzymes following four cycles of combined therapy with anti-PD-1(Pembrolizumab)and a tyrosine kinase inhibitor.Magne-tic resonance cholangiopancreatography indicated a thickening of the upper bile duct and pancreatic sections with narrow lumens.Digital peroral cholangioscopy revealed several erosions and surface vessel tortuosities coating the common bile duct.Endoscopic ultrasound revealed disruption of the middle lumen segment,with poorly defined wall structures.Endoscopic retrograde cholangiopancreato-graphy(ERCP)demonstrated mucosal irregularities with tortuous surface vessels along the common bile duct.Angiographic imaging revealed irregular defects in the middle and lower common bile duct segments,while the proximal duct exhibited multifocal stenosis alternating with dilatation.Biopsy samples obtained via ERCP from the elevated mucosal lesions showed dense epithelial inflam-matory cell infiltration,consistent with immune-related cholangitis.Both biliary enzymes can be decreased to a certain degree by corticosteroid and ursodeoxy-cholic acid therapy but are difficult to reduce to normal levels.Liver function normalized,and symptoms improved after local treatment for cholestasis(stent implantation).CONCLUSION Stent placement offers prompt alleviation of cholestasis and constitutes an effective therapeutic strategy for managing immune-related cholangitis.
文摘Primary biliary cholangitis(PBC)is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction,leading to fibrosis,cirrhosis,and eventual liver failure.Over the past two decades,significant advancements have paved the way for novel therapeutic strategies.Ursodeoxycholic acid(UDCA)has been the cornerstone of PBC management,improving survival and delaying disease progression in most patients.However,up to 40%of patients demonstrate an inadequate response to UDCA,necessitating additional treatment options.Obeticholic acid(OCA),a farnesoid X receptor agonist,has emerged as a second-line therapy,showing efficacy in reducing alkaline phosphatase levels and improving liver biochemistry.Beyond UDCA and OCA,a new wave of therapeutic agents are reshaping the PBC landscape.These include fibrates,peroxisome proliferator-activated receptor agonists and novel immunomodulatory drugs aimed at reducing autoimmune-mediated liver injury.Bile acid transport inhibitors,anti-fibrotic agents,and gut microbiome-targeted therapies are also under investigation,offering hope for personalized treatment approaches.This review highlights the evolution of PBC therapy,emphasizing the unmet needs of patients with refractory disease and the potential of emerging therapies to improve outcomes.As the therapeutic landscape continues to expand,optimizing treatment strategies through precision medicine holds the promise of transforming the management of PBC.
基金Supported by National Natural Science Foundation of China,No.82172257Health Care Major Project of Guangzhou,No.202206080001Science and Technology Cooperation Program of Fujian Province,No.2021I0036。
文摘BACKGROUND The diagnosis of primary biliary cholangitis(PBC)remains challenging,particularly in cases where anti-mitochondrial antibody(AMA),anti-mitochondrial E2 subunit antibody(AMA-M2),anti-glycoprotein 210(anti-gp210),and anti-speckled protein 100(anti-Sp100)are all negative.In such instances,the condition is often confirmed through a liver needle biopsy.AIM To identify additional plasma biomarkers for non-invasive diagnostic methods of PBC.METHODS We utilized the Sengenics KREX^(TM)immunome protein array to identify potential biomarkers for the diagnosis of PBC.Subsequently,we validated the predictive capability of the RPL30 antibody through an ELISA and retrospectively analyzed its association with the clinical features of 17 autoantibody-negative PBC cases and 45 autoantibody-positive PBC cases.RESULTS In our study we observed that RPL30 demonstrated the highest fold-change difference in PBC,with a penetrance frequency of 40%and a penetrance fold change of 38.30147.The analysis of anti-RPL30 optical density values between patients with AMA/AMA-M2/anti-gp210/anti-Sp100-negative PBC(autoantibody-negative PBC)and healthy controls using a receiver operating characteristic curve yielded an area under the curve of 0.853.This analysis established an optimal cutoff value of 0.0708,achieving 100%specificity and 75%sensitivity.The combination of anti-RPL30 and other autoantibodies elevated the diagnosis rate of PBC from 61.29%to 79.00%(P=0.0489).Anti-RPL30 demonstrated a high positive rate in antibody-negative PBC cases,including AMA/AMAM2/anti-gp210/anti-Sp100-negative cases.Correlation analysis of anti-RPL30 optical density values with clinical data from patients with PBC revealed a positive association with both the international normalized ratio(P=0.008)and the Model for End-Stage Liver Disease score(P=0.003).CONCLUSION Our study highlighted the potential of anti-RPL30 as a promising biomarker for diagnosing PBC,particularly in autoantibody-negative cases.
基金National Key Research and Development Program of China(No.2022YFE0203600,China)National Natural Science Foundation of China(Nos.82341232,81925035)+3 种基金Department of Science and Technology of Guangdong Province(No.2021B0909050003)Chinese Academy of Sciences President's International Fellowship Initiative(No.2024VBB0004)the Scientific Innovation Group Project in Zhongshan(No.CXTD2022011)supported by grants from the Program of Shanghai Committee of Science and Technology,China(No.22S21902900)。
文摘The concurrence of primary sclerosing cholangitis(PSC)and inflammatory bowel disease(IBD)presents a therapeutic challenge,often necessitating liver transplantation in severe cases.Paeoniflorin(PAE),known for its immunomodulatory and anti-inflammatory properties but with very high-water solubility and low permeability,is formulated into a paeoniflorin/phospholipid complex microemulsion(PAE-ME)to enhance its delivery in this study.It demonstrated the PAE-ME's macrophage-regulating ability to repolarize the pro-inflammatory M1 subtype to the anti-inflammatory M2 type and reduce inflammatory cytokine release.In a PSC-IBD mouse model,PAE-ME alleviated the symptoms and regulated bile acid balance.Given the close connection and crosstalk between the liver and intestine,PAE-ME yielded a synergistic therapeutic effect on both the liver and intestinal lesions.These findings suggest a promising translational approach for complex comorbidities by acting on the liver-gut axis.
基金Supported by Guangdong Provincial Basic and Applied Basic Research Fund,No.2021A1515011589Guangdong Medical University Clinical+Basic Science and Technology Innovation Special Program,No.GDMULCJC2024004.
文摘BACKGROUND T helper 17(Th17)cell infiltration and interleukin(IL)-17 secretion in intrahepatic small bile ducts is a critical driver of immune-mediated injury in primary biliary cholangitis(PBC).IL-6 is an essential upstream activator of Th17 cells.Basophilderived IL-6 promotes the differentiation of CD4+T cells and Th1 cells into Th17 cells,thereby regulating their immunological functions.AIM To investigate the activation status and cytokine expression of basophils in PBC,elucidating potential mechanisms through which basophils contribute to its pathogenesis.METHODS This single-center retrospective case-control study conducted at Guangdong Medical University Affiliated Hospital(China)between September 2019 and August 2024 enrolled 65 consecutive treatment-naïve patients with PBC(PBC group),65 age-and sex-matched patients with chronic hepatitis B(CHB group),and 65 healthy controls(Normal group).Fourteen participants per group(subgroup)were randomly selected for flow cytometry analysis of basophil proportion,activation markers(CD203c and CD62 L mean fluorescence intensity),IL-6-positive basophils(IL-6+basophils as a percentage of total basophils),and IL-17-positive T lymphocytes(CD3+CD4+IL-17+cells)proportion among T cells.Data were analyzed using Kruskal-Wallis and χ^(2) tests as appropriate.RESULTS Routine blood tests revealed significantly higher basophil counts and proportions in the PBC group compared to the CHB and Normal groups(P<0.001 for both comparisons),with no significant differences between the CHB and Normal groups(P=0.201).Flow cytometry revealed a higher basophil proportion in the PBC subgroup compared to the CHB(P=0.011)and Normal subgroups(P<0.001).The mean fluorescence intensity of CD203c on basophil surfaces was elevated in the PBC subgroup compared to the CHB(P=0.032)and Normal subgroups(P=0.039).The proportion of IL-6+basophils was significantly higher in the PBC subgroup than in the CHB(P<0.01)and Normal subgroups(P<0.001).Similarly,the Th17 cell proportion was markedly elevated in the PBC compared to the CHB(P<0.001)and Normal subgroups(P<0.001).CONCLUSION Patients with PBC have increased peripheral basophil counts with enhanced activation.Activated basophils have increased IL-6 expression,which may indirectly induce Th17 cell proliferation and contribute to PBC pathogenesis.
