Radiological imaging findings may contribute to the differentiation of malignant biliary obstruction from choledocholithiasis in the etiology of acute cholangitis.
BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provid...BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.展开更多
BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV t...BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.展开更多
Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Me...Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Methods:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020.We analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and prognosis.Results:A total of 32 ASTC patients were included in the analysis.The majority of the patients had a history of biliary operations,and clinical manifestations were occult and atypical.The positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance imaging.Treatment with effective antibiotics was provided as soon as diagnosis was established.After treatment,most patients had a good outcome.Elevated levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis.Conclusions:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.展开更多
Chronic liver diseases,including primary biliary cholangitis(PBC),are recognized as immunosuppressive conditions due to the impaired functionality of hepatic sinusoidal Kupffer cells.[1]PBC is specifically characteriz...Chronic liver diseases,including primary biliary cholangitis(PBC),are recognized as immunosuppressive conditions due to the impaired functionality of hepatic sinusoidal Kupffer cells.[1]PBC is specifically characterized by cholangitis and progressive liver pathology,which may eventually lead to cirrhosis.The compromised liver function and reduced efficacy of Kupffer cells in patients with PBC weaken their cell-mediated immune responses,increasing their susceptibility to opportunistic pathogens such as Cryptococcus.[2]Cryptococcosis is an infectious disease caused by pathogenic encapsulated yeasts of the genus Cryptococcus,which is distributed worldwide and exhibits diverse clinical presentations.[3]Most case reports on cryptococcal infections are associated with HIV infection or other conditions that compromise the immune system.[4]Case reports related to primary biliary cholangitis are rare.Therefore,this case report underscores a rare cryptococcal infection in a patient with primary biliary cholangitis,emphasizing the need to consider opportunistic infections in those with compromised liver function and immune dysregulation.展开更多
BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune...BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.展开更多
Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation...Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.展开更多
BACKGROUND During emergency endoscopic retrograde cholangiopancreatography(ERCP),the safety and feasibility of performing one-stage endoscopic treatment for patients with acute cholangitis(AC)due to choledocholithiasi...BACKGROUND During emergency endoscopic retrograde cholangiopancreatography(ERCP),the safety and feasibility of performing one-stage endoscopic treatment for patients with acute cholangitis(AC)due to choledocholithiasis are unclear.AIM To investigate the safety and feasibility of one-stage endoscopic treatment for moderate to severe AC.METHODS We enrolled all patients diagnosed with moderate to severe cholangitis due to common bile duct stones from January 2019 to July 2023.The outcomes were compared in this study between patients who underwent ERCP within 24 h and those who underwent ERCP 24 h later,employing a propensity score(PS)frame-work.Our primary outcomes were intensive care unit(ICU)admission rates,ICU length of stay,and duration of antibiotic use.RESULTS In total,we included 254 patients and categorized them into two groups based on the time elapsed between admission and intervention:The urgent group(≤24 h,n=102)and the elective group(>24 h,n=152).Ninety-three pairs of patients with similar characteristics were selected by PS matching.The urgent ERCP group had more ICU admissions(34.4%vs 21.5%,P=0.05),shorter ICU stays(3 d vs 9 d,P<0.001),fewer antibiotic use(6 d vs 9 d,P<0.001),and shorter hospital stays(9 d vs 18.5 d,P<0.001).There were no significant differences observed in adverse events,in-hospital mortality,recurrent cholangitis occurrence,30-d readmission rate or 30-d mortality.CONCLUSION Urgent one-stage ERCP provides the advantages of a shorter ICU stay,a shorter duration of antibiotic use,and a shorter hospital stay.展开更多
Background: It is crucial to assess the severity of acute cholangitis(AC). There are currently several prognostic markers. However, the accuracies of these markers are not satisfied. The present study aimed to investi...Background: It is crucial to assess the severity of acute cholangitis(AC). There are currently several prognostic markers. However, the accuracies of these markers are not satisfied. The present study aimed to investigate the predictive value of the red cell distribution width(RDW)-to-albumin ratio(RAR) for the prognosis of AC. Methods: We retrospectively evaluated consecutive patients diagnosed with AC between May 2019 and March 2022. RAR was calculated, and its predictive ability for in-hospital mortality, intensive care unit(ICU) admission, bacteremia, and the length of hospitalization were analyzed. Results: Out of 438 patients, 34(7.8%) died. Multivariate analysis showed that malignant etiology [odds ratio(OR) = 4.816, 95% confidence interval(CI): 1.936-11.980], creatinine(OR = 1.649, 95% CI: 1.095-2.484), and RAR(OR = 2.064, 95% CI: 1.494-2.851) were independent risk factors for mortality. When adjusted for relevant covariates, including age, sex, malignant etiology, Tokyo severity grading(TSG), Charlson comorbidity index, and creatinine, RAR significantly predicted mortality(adjusted OR = 1.833, 95% CI: 1.280-2.624). When the cut-off of RAR was set to 3.8, its sensitivity and specificity for mortality were 94.1% and 56.7%, respectively. Patients with an RAR of > 3.8 had a 20.9-fold(OR = 20.9, 95% CI: 4.9-88.6) greater risk of mortality than the remaining patients. The area under the curve value of RAR for mortality was 0.835(95% CI: 0.770-0.901), which was significantly higher than that of TSG and the other prognostic markers, such as C-reactive protein-to-albumin ratio, and procalcitonin-to-albumin ratio. Lastly, RAR was not inferior to TSG in predicting ICU admission, bacteremia, and the length of hospitalization. Conclusions: RAR successfully predicted the in-hospital mortality, ICU admission, bacteremia, and the length of hospitalization of patients with AC, especially in-hospital mortality. RAR is a promising marker that is more convenient than TSG and other prognostic markers for predicting the prognosis of patients with AC.展开更多
Background:Primary biliary cholangitis(PBC)is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis.Swertia mussotii Franch.(SMF)is a Tibetan medicine with hepatoprotective and anti-infl...Background:Primary biliary cholangitis(PBC)is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis.Swertia mussotii Franch.(SMF)is a Tibetan medicine with hepatoprotective and anti-inflammatory activities.In this study,the therapeutic effect and potential mechanisms of SMF on PBC were investigated by bioinformatics analysis and in vitro experimental validation,with the aim of promoting the progress of SMF and PBC research.Methods:We first explored the therapeutic effects and key targets of SMF on PBC using a network pharmacology approach,further screened the core targets using the GSE79850 dataset,and finally validated the results using molecular docking techniques and in vitro experiments.Results:By bioinformatics analysis,we identified core targets of SMF for PBC treatment(STAT3,JAK2,TNF-α,and IL-1β)and important signaling pathways:JAK-STAT,TNF,and PI3K-AKT.The molecular docking results showed that the significant components of SMF had good binding properties to the core targets.In vitro experiments showed that SMF extracts improved the extent of epithelial-mesenchymal transition in human intrahepatic biliary epithelial cells and had a significant reversal effect on epithelial-mesenchymal transition process markers and potential targets in PBC.Conclusion:SMF may exert its therapeutic effects on PBC by acting on important targets such as STAT3,JAK2,TNF-α,IL-1β,Vimentin,and E-cadherin and the pathways in which they are involved.展开更多
BACKGROUND Acute cholangitis(AC)constitutes an infection with increased mortality rates in the past.Due to new diagnostic tools and therapeutic methods,the mortality of AC has been significantly reduced nowadays.The i...BACKGROUND Acute cholangitis(AC)constitutes an infection with increased mortality rates in the past.Due to new diagnostic tools and therapeutic methods,the mortality of AC has been significantly reduced nowadays.The initial antibiotic treatment of AC has been oriented to the most common pathogens connected to this infection.However,the optimal duration of the antibiotic treatment of AC is still debatable.AIM To investigate if shorter-course antibiotic treatments could be similarly effective to long-course treatments in adults with AC.METHODS This study constitutes a systematic review and meta-analysis of the existing literature concerning the duration of antibiotic therapy of AC and an assessment of the quality of the evidence.The study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analyses.Fifteen studies were included in the systematic review,and eight were eligible for meta-analysis.Due to heterogeneous duration cutoffs,three study-analysis groups were formed,with a cutoff of 2-3,6-7,and 14 d.RESULTS A total of 2763 patients were included in the systematic review,and 1313 were accounted for the meta-analysis.The mean age was 73.66±14.67 years,and the male and female ratio was 1:08.No significant differences were observed in the mortality rates of antibiotic treatment of 2-3 d,compared to longer treatments(odds ratio=0.78,95% confidence interval:0.23-2.67,I2=9%)and the recurrence rates and hospitalization length were also not different in all study groups.CONCLUSION Short-and long-course antibiotic treatments may be similarly effective concerning the mortality and recurrence rates of AC.Safe conclusions cannot be extracted concerning the hospitalization duration.展开更多
BACKGROUND Osteoporosis is an extrahepatic complication of primary biliary cholangitis(PBC)that increases the risk of fractures and mortality.However,Epidemiological studies of osteoporosis in patients with PBC in Chi...BACKGROUND Osteoporosis is an extrahepatic complication of primary biliary cholangitis(PBC)that increases the risk of fractures and mortality.However,Epidemiological studies of osteoporosis in patients with PBC in China and the Asia-Pacific region is lack.AIM To assess the prevalence and clinical characteristics of osteoporosis in Chinese patients with PBC.METHODS This retrospective analysis included consecutive patients with PBC from a tertiary care center in China who underwent bone mineral density(BMD)assessment using dual-energy X-ray absorptiometry between January 2013 and December 2021.We defined subjects with T-scores≤-2.5 in any sites(L1 to L4,femoral neck,or total hip)as having osteoporosis.Demographic,serological,clinical,and histological data were collected.Independent risk factors for osteoporosis were identified by multivariate logistic regression analysis.RESULTS A total of 268 patients with PBC[236 women(88.1%);mean age,56.7±10.6 years;163 liver biopsies(60.8%)]were included.The overall prevalence of osteoporosis in patients with PBC was 45.5%(122/268),with the prevalence of osteoporosis in women and men being 47.0%and 34.4%,respectively.The prevalence of osteoporosis in postmenopausal women was significantly higher than that in premenopausal women(56.3%vs 21.0%,P<0.001).Osteoporosis in patients with PBC is associated with age,fatigue,menopausal status,previous steroid therapy,body mass index(BMI),splenomegaly,gastroesophageal varices,ascites,Mayo risk score,histological stage,alanine aminotransferase,albumin,bilirubin,platelet and prothrombin activity.Multivariate regression analysis identified that older age,lower BMI,previous steroid therapy,higher Mayo risk score,and advanced histological stage as the main independent risk factors for osteoporosis in PBC.CONCLUSION Osteoporosis is very common in Chinese patients with PBC,allowing for prior screening of BMD in those PBC patients with older age,lower BMI,previous steroid therapy and advanced liver disease.展开更多
BACKGROUND Elective cholecystectomy(CCY)is recommended for patients with gallstone-related acute cholangitis(AC)following endoscopic decompression to prevent recurrent biliary events.However,the optimal timing and imp...BACKGROUND Elective cholecystectomy(CCY)is recommended for patients with gallstone-related acute cholangitis(AC)following endoscopic decompression to prevent recurrent biliary events.However,the optimal timing and implications of CCY remain unclear.AIM To examine the impact of same-admission CCY compared to interval CCY on patients with gallstone-related AC using the National Readmission Database(NRD).METHODS We queried the NRD to identify all gallstone-related AC hospitalizations in adult patients with and without the same admission CCY between 2016 and 2020.Our primary outcome was all-cause 30-d readmission rates,and secondary outcomes included in-hospital mortality,length of stay(LOS),and hospitalization cost.RESULTS Among the 124964 gallstone-related AC hospitalizations,only 14.67%underwent the same admission CCY.The all-cause 30-d readmissions in the same admission CCY group were almost half that of the non-CCY group(5.56%vs 11.50%).Patients in the same admission CCY group had a longer mean LOS and higher hospitalization costs attrib-utable to surgery.Although the most common reason for readmission was sepsis in both groups,the second most common reason was AC in the interval CCY group.CONCLUSION Our study suggests that patients with gallstone-related AC who do not undergo the same admission CCY have twice the risk of readmission compared to those who undergo CCY during the same admission.These readmis-sions can potentially be prevented by performing same-admission CCY in appropriate patients,which may reduce subsequent hospitalization costs secondary to readmissions.展开更多
BACKGROUND Whether clinical outcomes of acute cholangitis(AC)vary by etiology is unclear.AIM To compare outcomes in AC caused by malignant biliary obstruction(MBO)and common bile duct stones(CBDS).METHODS This retrosp...BACKGROUND Whether clinical outcomes of acute cholangitis(AC)vary by etiology is unclear.AIM To compare outcomes in AC caused by malignant biliary obstruction(MBO)and common bile duct stones(CBDS).METHODS This retrospective study included 516 patients undergoing endoscopic retrograde cholangiopancreatography(ERCP)due to AC caused by MBO(MBO group,n=56)and CBDS(CBDS group,n=460).Clinical and laboratory parameters were compared between the groups.Propensity score matching(PSM)created 55 matched pairs.Confounders used in the PSM analysis were age,sex,time to ERCP,and technical success of ERCP.The primary outcome comparison was 30-d mortality.The secondary outcome comparisons were intensive care unit(ICU)admission rate,length of hospital stay(LOHS),and 30-d readmission rate.RESULTS Compared with the CBDS group,the MBO group had significantly lower body temperature,percentage of abnormal white blood cell counts,and serum levels of aspartate aminotransferase,alanine aminotransferase,and creatinine.Body temperature,percent abnormal white blood cell count,and serum aspartate aminotransferase levels remained significantly lower in the MBO group in the PSM analysis.Platelet count,prothrombin time/international normalized ratio,and serum levels of alkaline phosphatase and total bilirubin were significantly higher in the MBO group.The MBO group had a significantly higher percentage of severe AC(33.9%vs 22.0%,P=0.045)and received ERCP later(median,92.5 h vs 47.4 h,P<0.001).However,the two differences were not found in the PSM analysis.The 30-d mortality(5.4%vs 0.7%,P=0.019),ICU admission rates(12.5%vs 4.8%,P=0.028),30-d readmission rates(23.2%vs 8.0%,P<0.001),and LOHS(median,16.5 d vs 7.0 d,P<0.001)were significantly higher or longer in the MBO group.However,only LOHS remained significant in the PSM analysis.Multivariate analysis revealed that time to ERCP and multiple organ dysfunction were independent factors associated with 30-d mortality.CONCLUSION MBO patients underwent ERCP later and thus had a worse prognosis than CBDS patients.Therefore,clinicians should remain vigilant in MBO patients with clinically suspected AC,and perform ERCP for biliary drainage as soon as possible.展开更多
BACKGROUND Primary sclerosing cholangitis(PSC)manifests within a broad ethnic and racial spectrum,reflecting different levels of access to health care.AIM To evaluate the clinical profile,complications and survival ra...BACKGROUND Primary sclerosing cholangitis(PSC)manifests within a broad ethnic and racial spectrum,reflecting different levels of access to health care.AIM To evaluate the clinical profile,complications and survival rates of patients with PSC undergoing liver transplantation(LTx)at a Brazilian reference center.METHODS All patients diagnosed with PSC before or after LTx were included.The medical records were reviewed for demographic and clinical variables,including outcomes and survival.The level of statistical significance was set at P<0.05.RESULTS Our cohort represented 1.6%(n=34)of the 2113 patients receiving liver grafts at our service over the past two decades.Most were male(n=19;56%).The average age(40±14 years)was similar for men and women(P=0.347).The mean follow-up time from diagnosis to LTx was 68 mo.Most patients had the classic form of PSC.Three women had PSC/autoimmune hepatitis overlap syndrome,and one patient had small-duct PSC.Alkaline phosphatase levels at diagnosis and pre-LTx model for end-stage liver disease.scores were significantly higher in males.Inflammatory bowel research(IBD)was investigated by colonoscopy in 26/34(76%)and was present in most cases(18/26;69%).IBD was less common in women than in men(44.4%vs.55.6%)(P=0.692).Cholangiocarcinoma(CCA)was diagnosed in 2/34(5.9%)patients by histopathology of the explant(survival:3 years 6 mo,and 4 years 11 mo).Two patients had complications requiring a second LTx(one after 7 d due to hepatic artery thrombosis and one after 17 d due to primary graft dysfunction).Five patients(14.7%)developed biliary stricture.The overall median post-LTx survival was 66 mo.Most deaths occurred in the first year(infection n=2,primary liver graft dysfunction n=3,unknown cause n=1).The 1-year and 5-year survival rates of this cohort were 82.3%and 70.6%,respectively,matching the mean overall survival rates of LTx patients at our center(87.1%and 69.43%,respectively)(P=0.83).CONCLUSION Survival after 1 and 5 years was similar to that of other LTx indications.The observed CCA survival rate suggests CCA may be an indication for LTx in selected cases.展开更多
BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innat...BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innate immunity.Acylcarnitines are established mitochondrial biomarkers.AIM To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage.METHODS Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018.Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry,respectively.RESULTS The concentrations of presepsin,procalcitonin,short-and medium-chain acylcarnitines increased,while long-chain acylcarnitines decreased with the severity of acute cholangitis.The areas under the receiver operating characteristic curves(AUC)of presepsin for diagnosing moderate/severe and severe cholangitis(0.823 and 0.801,respectively)were greater than those of conventional markers.The combination of presepsin,direct bilirubin,alanine aminotransferase,temperature,and butyryl-L-carnitine showed good predictive ability for biliary drainage(AUC:0.723).Presepsin,procalcitonin,acetyl-L-carnitine,hydroxydodecenoyl-Lcarnitine,and temperature were independent predictors of bloodstream infection.After adjusting for severity classification,acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality(hazard ratio 14.396;P<0.001)(AUC:0.880).Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine.CONCLUSION Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage.Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis.Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.展开更多
BACKGROUND Due to the chronic progressive disease characteristics of primary biliary cholangitis(PBC),patients with advanced PBC should not be ignored.Most prognostic score studies have focused on early stage PBC.AIM ...BACKGROUND Due to the chronic progressive disease characteristics of primary biliary cholangitis(PBC),patients with advanced PBC should not be ignored.Most prognostic score studies have focused on early stage PBC.AIM To compare the prognostic value of various risk scores in advanced PBC to help PBC patients obtain more monitoring and assessment.METHODS This study considered patients diagnosed with PBC during hospitalization between 2015 and 2021.The clinical stage was primarily middle and late,and patients usually took ursodeoxycholic acid(UDCA)after diagnosis.The discriminatory performance of the scores was assessed with concordance statistics at baseline and after 1 year of UDCA treatment.Telephone follow-up was conducted to analyze the course and disease-associated outcomes.The follow-up deadline was December 31,2021.We compared the risk score indexes between those patients who reached a composite end point of death or liver transplantation(LT)and those who remained alive at the deadline.The combined performance of prognostic scores in estimating the risk of death or LT after 1 year of UDCA treatment was assessed using Cox regression analyses.Predictive accuracy was evaluated by comparing predicted and actual survival through Kaplan-Meier analyses.RESULTS We included 397 patients who were first diagnosed with PBC during hospitalization and received UDCA treatment;most disease stages were advanced.After an average of 6.4±1.4 years of follow-up,82 patients had died,and 4 patients had undergone LT.After receiving UDCA treatment for 1 year,the score with the best discrimination performance was the Mayo,with a concordance statistic of 0.740(95%confidence interval:0.690-0.791).The albumin-bilirubin,GLOBE,and Mayo scores tended to overestimate transplant-free survival.Comparing 7 years of calibration results showed that the Mayo score was the best model.CONCLUSION The Mayo,GLOBE,UK-PBC,and ALBI scores demonstrated comparable discriminating performance for advanced stage PBC.The Mayo score showed optimal discriminatory performance and excellent predictive accuracy.展开更多
文摘Radiological imaging findings may contribute to the differentiation of malignant biliary obstruction from choledocholithiasis in the etiology of acute cholangitis.
基金Supported by the National Natural Science Foundation of China,No.82172297Natural Science Foundation of Jiangsu Province of China,No.BK20211346 and No.BK20201011+1 种基金Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.22KJA310007Xuzhou Science and Technology Project,No.KC22055.
文摘BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.
文摘BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.
基金This study was supported by a grant from the National Natural Science Foundation of China(81870457).
文摘Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Methods:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020.We analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and prognosis.Results:A total of 32 ASTC patients were included in the analysis.The majority of the patients had a history of biliary operations,and clinical manifestations were occult and atypical.The positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance imaging.Treatment with effective antibiotics was provided as soon as diagnosis was established.After treatment,most patients had a good outcome.Elevated levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis.Conclusions:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.
基金supported by the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-007A)the China International Medical Foundation Project(Grant No.Z-2021-15-18)Tianjin Health Technology Project(Grant No.20188).
文摘Chronic liver diseases,including primary biliary cholangitis(PBC),are recognized as immunosuppressive conditions due to the impaired functionality of hepatic sinusoidal Kupffer cells.[1]PBC is specifically characterized by cholangitis and progressive liver pathology,which may eventually lead to cirrhosis.The compromised liver function and reduced efficacy of Kupffer cells in patients with PBC weaken their cell-mediated immune responses,increasing their susceptibility to opportunistic pathogens such as Cryptococcus.[2]Cryptococcosis is an infectious disease caused by pathogenic encapsulated yeasts of the genus Cryptococcus,which is distributed worldwide and exhibits diverse clinical presentations.[3]Most case reports on cryptococcal infections are associated with HIV infection or other conditions that compromise the immune system.[4]Case reports related to primary biliary cholangitis are rare.Therefore,this case report underscores a rare cryptococcal infection in a patient with primary biliary cholangitis,emphasizing the need to consider opportunistic infections in those with compromised liver function and immune dysregulation.
基金Supported by National Natural Science Foundation of China,No.82060123National Health Commission of Guizhou Province,No.gzwjk2019-1-082.
文摘BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.
基金supported by grants for National Key Research and Development Program of China(No.2020YFA0113003)Key Research and Development Project of Zhejiang Province(No.2023C03046)+1 种基金Fundamental Research Funds for the Central Universities(No.2022ZFJH003)Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2022026C,JNL-2023003C).
文摘Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.
基金The study was approved by the Ethics Committee(2019ZDSYLL094-P01).
文摘BACKGROUND During emergency endoscopic retrograde cholangiopancreatography(ERCP),the safety and feasibility of performing one-stage endoscopic treatment for patients with acute cholangitis(AC)due to choledocholithiasis are unclear.AIM To investigate the safety and feasibility of one-stage endoscopic treatment for moderate to severe AC.METHODS We enrolled all patients diagnosed with moderate to severe cholangitis due to common bile duct stones from January 2019 to July 2023.The outcomes were compared in this study between patients who underwent ERCP within 24 h and those who underwent ERCP 24 h later,employing a propensity score(PS)frame-work.Our primary outcomes were intensive care unit(ICU)admission rates,ICU length of stay,and duration of antibiotic use.RESULTS In total,we included 254 patients and categorized them into two groups based on the time elapsed between admission and intervention:The urgent group(≤24 h,n=102)and the elective group(>24 h,n=152).Ninety-three pairs of patients with similar characteristics were selected by PS matching.The urgent ERCP group had more ICU admissions(34.4%vs 21.5%,P=0.05),shorter ICU stays(3 d vs 9 d,P<0.001),fewer antibiotic use(6 d vs 9 d,P<0.001),and shorter hospital stays(9 d vs 18.5 d,P<0.001).There were no significant differences observed in adverse events,in-hospital mortality,recurrent cholangitis occurrence,30-d readmission rate or 30-d mortality.CONCLUSION Urgent one-stage ERCP provides the advantages of a shorter ICU stay,a shorter duration of antibiotic use,and a shorter hospital stay.
文摘Background: It is crucial to assess the severity of acute cholangitis(AC). There are currently several prognostic markers. However, the accuracies of these markers are not satisfied. The present study aimed to investigate the predictive value of the red cell distribution width(RDW)-to-albumin ratio(RAR) for the prognosis of AC. Methods: We retrospectively evaluated consecutive patients diagnosed with AC between May 2019 and March 2022. RAR was calculated, and its predictive ability for in-hospital mortality, intensive care unit(ICU) admission, bacteremia, and the length of hospitalization were analyzed. Results: Out of 438 patients, 34(7.8%) died. Multivariate analysis showed that malignant etiology [odds ratio(OR) = 4.816, 95% confidence interval(CI): 1.936-11.980], creatinine(OR = 1.649, 95% CI: 1.095-2.484), and RAR(OR = 2.064, 95% CI: 1.494-2.851) were independent risk factors for mortality. When adjusted for relevant covariates, including age, sex, malignant etiology, Tokyo severity grading(TSG), Charlson comorbidity index, and creatinine, RAR significantly predicted mortality(adjusted OR = 1.833, 95% CI: 1.280-2.624). When the cut-off of RAR was set to 3.8, its sensitivity and specificity for mortality were 94.1% and 56.7%, respectively. Patients with an RAR of > 3.8 had a 20.9-fold(OR = 20.9, 95% CI: 4.9-88.6) greater risk of mortality than the remaining patients. The area under the curve value of RAR for mortality was 0.835(95% CI: 0.770-0.901), which was significantly higher than that of TSG and the other prognostic markers, such as C-reactive protein-to-albumin ratio, and procalcitonin-to-albumin ratio. Lastly, RAR was not inferior to TSG in predicting ICU admission, bacteremia, and the length of hospitalization. Conclusions: RAR successfully predicted the in-hospital mortality, ICU admission, bacteremia, and the length of hospitalization of patients with AC, especially in-hospital mortality. RAR is a promising marker that is more convenient than TSG and other prognostic markers for predicting the prognosis of patients with AC.
基金supported by the Key project of Chinese Academy of Sciences(Grant No.ZDRW-ZS-2020-2)Innovation Platform Program of Qinghai Province(2021-ZJ-T02),Key Laboratory Project of Qinghai Province(2022-ZJ-Y05)+1 种基金the Natural Science Foundation of China(Grant No.82171863)China Postdoctoral Science Foundation funded project(2021M701642).
文摘Background:Primary biliary cholangitis(PBC)is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis.Swertia mussotii Franch.(SMF)is a Tibetan medicine with hepatoprotective and anti-inflammatory activities.In this study,the therapeutic effect and potential mechanisms of SMF on PBC were investigated by bioinformatics analysis and in vitro experimental validation,with the aim of promoting the progress of SMF and PBC research.Methods:We first explored the therapeutic effects and key targets of SMF on PBC using a network pharmacology approach,further screened the core targets using the GSE79850 dataset,and finally validated the results using molecular docking techniques and in vitro experiments.Results:By bioinformatics analysis,we identified core targets of SMF for PBC treatment(STAT3,JAK2,TNF-α,and IL-1β)and important signaling pathways:JAK-STAT,TNF,and PI3K-AKT.The molecular docking results showed that the significant components of SMF had good binding properties to the core targets.In vitro experiments showed that SMF extracts improved the extent of epithelial-mesenchymal transition in human intrahepatic biliary epithelial cells and had a significant reversal effect on epithelial-mesenchymal transition process markers and potential targets in PBC.Conclusion:SMF may exert its therapeutic effects on PBC by acting on important targets such as STAT3,JAK2,TNF-α,IL-1β,Vimentin,and E-cadherin and the pathways in which they are involved.
文摘BACKGROUND Acute cholangitis(AC)constitutes an infection with increased mortality rates in the past.Due to new diagnostic tools and therapeutic methods,the mortality of AC has been significantly reduced nowadays.The initial antibiotic treatment of AC has been oriented to the most common pathogens connected to this infection.However,the optimal duration of the antibiotic treatment of AC is still debatable.AIM To investigate if shorter-course antibiotic treatments could be similarly effective to long-course treatments in adults with AC.METHODS This study constitutes a systematic review and meta-analysis of the existing literature concerning the duration of antibiotic therapy of AC and an assessment of the quality of the evidence.The study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analyses.Fifteen studies were included in the systematic review,and eight were eligible for meta-analysis.Due to heterogeneous duration cutoffs,three study-analysis groups were formed,with a cutoff of 2-3,6-7,and 14 d.RESULTS A total of 2763 patients were included in the systematic review,and 1313 were accounted for the meta-analysis.The mean age was 73.66±14.67 years,and the male and female ratio was 1:08.No significant differences were observed in the mortality rates of antibiotic treatment of 2-3 d,compared to longer treatments(odds ratio=0.78,95% confidence interval:0.23-2.67,I2=9%)and the recurrence rates and hospitalization length were also not different in all study groups.CONCLUSION Short-and long-course antibiotic treatments may be similarly effective concerning the mortality and recurrence rates of AC.Safe conclusions cannot be extracted concerning the hospitalization duration.
基金Capital’s Funds for Health Improvement and Research,No.CFH2018-1-2172Beijing Ditan Hospital Scientific Research Fund Project,No.DTYM202102.
文摘BACKGROUND Osteoporosis is an extrahepatic complication of primary biliary cholangitis(PBC)that increases the risk of fractures and mortality.However,Epidemiological studies of osteoporosis in patients with PBC in China and the Asia-Pacific region is lack.AIM To assess the prevalence and clinical characteristics of osteoporosis in Chinese patients with PBC.METHODS This retrospective analysis included consecutive patients with PBC from a tertiary care center in China who underwent bone mineral density(BMD)assessment using dual-energy X-ray absorptiometry between January 2013 and December 2021.We defined subjects with T-scores≤-2.5 in any sites(L1 to L4,femoral neck,or total hip)as having osteoporosis.Demographic,serological,clinical,and histological data were collected.Independent risk factors for osteoporosis were identified by multivariate logistic regression analysis.RESULTS A total of 268 patients with PBC[236 women(88.1%);mean age,56.7±10.6 years;163 liver biopsies(60.8%)]were included.The overall prevalence of osteoporosis in patients with PBC was 45.5%(122/268),with the prevalence of osteoporosis in women and men being 47.0%and 34.4%,respectively.The prevalence of osteoporosis in postmenopausal women was significantly higher than that in premenopausal women(56.3%vs 21.0%,P<0.001).Osteoporosis in patients with PBC is associated with age,fatigue,menopausal status,previous steroid therapy,body mass index(BMI),splenomegaly,gastroesophageal varices,ascites,Mayo risk score,histological stage,alanine aminotransferase,albumin,bilirubin,platelet and prothrombin activity.Multivariate regression analysis identified that older age,lower BMI,previous steroid therapy,higher Mayo risk score,and advanced histological stage as the main independent risk factors for osteoporosis in PBC.CONCLUSION Osteoporosis is very common in Chinese patients with PBC,allowing for prior screening of BMD in those PBC patients with older age,lower BMI,previous steroid therapy and advanced liver disease.
文摘BACKGROUND Elective cholecystectomy(CCY)is recommended for patients with gallstone-related acute cholangitis(AC)following endoscopic decompression to prevent recurrent biliary events.However,the optimal timing and implications of CCY remain unclear.AIM To examine the impact of same-admission CCY compared to interval CCY on patients with gallstone-related AC using the National Readmission Database(NRD).METHODS We queried the NRD to identify all gallstone-related AC hospitalizations in adult patients with and without the same admission CCY between 2016 and 2020.Our primary outcome was all-cause 30-d readmission rates,and secondary outcomes included in-hospital mortality,length of stay(LOS),and hospitalization cost.RESULTS Among the 124964 gallstone-related AC hospitalizations,only 14.67%underwent the same admission CCY.The all-cause 30-d readmissions in the same admission CCY group were almost half that of the non-CCY group(5.56%vs 11.50%).Patients in the same admission CCY group had a longer mean LOS and higher hospitalization costs attrib-utable to surgery.Although the most common reason for readmission was sepsis in both groups,the second most common reason was AC in the interval CCY group.CONCLUSION Our study suggests that patients with gallstone-related AC who do not undergo the same admission CCY have twice the risk of readmission compared to those who undergo CCY during the same admission.These readmis-sions can potentially be prevented by performing same-admission CCY in appropriate patients,which may reduce subsequent hospitalization costs secondary to readmissions.
基金This study was reviewed and approved by the Ethics Committee of the Chang Gung Memorial Hospital(IRB No.202201601B0).
文摘BACKGROUND Whether clinical outcomes of acute cholangitis(AC)vary by etiology is unclear.AIM To compare outcomes in AC caused by malignant biliary obstruction(MBO)and common bile duct stones(CBDS).METHODS This retrospective study included 516 patients undergoing endoscopic retrograde cholangiopancreatography(ERCP)due to AC caused by MBO(MBO group,n=56)and CBDS(CBDS group,n=460).Clinical and laboratory parameters were compared between the groups.Propensity score matching(PSM)created 55 matched pairs.Confounders used in the PSM analysis were age,sex,time to ERCP,and technical success of ERCP.The primary outcome comparison was 30-d mortality.The secondary outcome comparisons were intensive care unit(ICU)admission rate,length of hospital stay(LOHS),and 30-d readmission rate.RESULTS Compared with the CBDS group,the MBO group had significantly lower body temperature,percentage of abnormal white blood cell counts,and serum levels of aspartate aminotransferase,alanine aminotransferase,and creatinine.Body temperature,percent abnormal white blood cell count,and serum aspartate aminotransferase levels remained significantly lower in the MBO group in the PSM analysis.Platelet count,prothrombin time/international normalized ratio,and serum levels of alkaline phosphatase and total bilirubin were significantly higher in the MBO group.The MBO group had a significantly higher percentage of severe AC(33.9%vs 22.0%,P=0.045)and received ERCP later(median,92.5 h vs 47.4 h,P<0.001).However,the two differences were not found in the PSM analysis.The 30-d mortality(5.4%vs 0.7%,P=0.019),ICU admission rates(12.5%vs 4.8%,P=0.028),30-d readmission rates(23.2%vs 8.0%,P<0.001),and LOHS(median,16.5 d vs 7.0 d,P<0.001)were significantly higher or longer in the MBO group.However,only LOHS remained significant in the PSM analysis.Multivariate analysis revealed that time to ERCP and multiple organ dysfunction were independent factors associated with 30-d mortality.CONCLUSION MBO patients underwent ERCP later and thus had a worse prognosis than CBDS patients.Therefore,clinicians should remain vigilant in MBO patients with clinically suspected AC,and perform ERCP for biliary drainage as soon as possible.
基金reviewed and approved by the ethics committee of the Federal University of Cearáand filed under Approval No.98627218.6.2018.5045.
文摘BACKGROUND Primary sclerosing cholangitis(PSC)manifests within a broad ethnic and racial spectrum,reflecting different levels of access to health care.AIM To evaluate the clinical profile,complications and survival rates of patients with PSC undergoing liver transplantation(LTx)at a Brazilian reference center.METHODS All patients diagnosed with PSC before or after LTx were included.The medical records were reviewed for demographic and clinical variables,including outcomes and survival.The level of statistical significance was set at P<0.05.RESULTS Our cohort represented 1.6%(n=34)of the 2113 patients receiving liver grafts at our service over the past two decades.Most were male(n=19;56%).The average age(40±14 years)was similar for men and women(P=0.347).The mean follow-up time from diagnosis to LTx was 68 mo.Most patients had the classic form of PSC.Three women had PSC/autoimmune hepatitis overlap syndrome,and one patient had small-duct PSC.Alkaline phosphatase levels at diagnosis and pre-LTx model for end-stage liver disease.scores were significantly higher in males.Inflammatory bowel research(IBD)was investigated by colonoscopy in 26/34(76%)and was present in most cases(18/26;69%).IBD was less common in women than in men(44.4%vs.55.6%)(P=0.692).Cholangiocarcinoma(CCA)was diagnosed in 2/34(5.9%)patients by histopathology of the explant(survival:3 years 6 mo,and 4 years 11 mo).Two patients had complications requiring a second LTx(one after 7 d due to hepatic artery thrombosis and one after 17 d due to primary graft dysfunction).Five patients(14.7%)developed biliary stricture.The overall median post-LTx survival was 66 mo.Most deaths occurred in the first year(infection n=2,primary liver graft dysfunction n=3,unknown cause n=1).The 1-year and 5-year survival rates of this cohort were 82.3%and 70.6%,respectively,matching the mean overall survival rates of LTx patients at our center(87.1%and 69.43%,respectively)(P=0.83).CONCLUSION Survival after 1 and 5 years was similar to that of other LTx indications.The observed CCA survival rate suggests CCA may be an indication for LTx in selected cases.
基金National Natural Science Foundation of China,No.81773931Beijing Municipal Administration of Hospitals’ Youth Program,No.QML20170105Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support "Yangfan" Project,No.ZYLX201804
文摘BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innate immunity.Acylcarnitines are established mitochondrial biomarkers.AIM To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage.METHODS Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018.Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry,respectively.RESULTS The concentrations of presepsin,procalcitonin,short-and medium-chain acylcarnitines increased,while long-chain acylcarnitines decreased with the severity of acute cholangitis.The areas under the receiver operating characteristic curves(AUC)of presepsin for diagnosing moderate/severe and severe cholangitis(0.823 and 0.801,respectively)were greater than those of conventional markers.The combination of presepsin,direct bilirubin,alanine aminotransferase,temperature,and butyryl-L-carnitine showed good predictive ability for biliary drainage(AUC:0.723).Presepsin,procalcitonin,acetyl-L-carnitine,hydroxydodecenoyl-Lcarnitine,and temperature were independent predictors of bloodstream infection.After adjusting for severity classification,acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality(hazard ratio 14.396;P<0.001)(AUC:0.880).Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine.CONCLUSION Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage.Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis.Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.
基金Medicine Leading Talents of Yunnan Province,No.L-2019013the Yunnan Wanren Project,No.YNWR-MY-2018-028and Clinical Research Project of the Second Affiliated Hospital of Kunming Medical University,No.2020ynlc010.
文摘BACKGROUND Due to the chronic progressive disease characteristics of primary biliary cholangitis(PBC),patients with advanced PBC should not be ignored.Most prognostic score studies have focused on early stage PBC.AIM To compare the prognostic value of various risk scores in advanced PBC to help PBC patients obtain more monitoring and assessment.METHODS This study considered patients diagnosed with PBC during hospitalization between 2015 and 2021.The clinical stage was primarily middle and late,and patients usually took ursodeoxycholic acid(UDCA)after diagnosis.The discriminatory performance of the scores was assessed with concordance statistics at baseline and after 1 year of UDCA treatment.Telephone follow-up was conducted to analyze the course and disease-associated outcomes.The follow-up deadline was December 31,2021.We compared the risk score indexes between those patients who reached a composite end point of death or liver transplantation(LT)and those who remained alive at the deadline.The combined performance of prognostic scores in estimating the risk of death or LT after 1 year of UDCA treatment was assessed using Cox regression analyses.Predictive accuracy was evaluated by comparing predicted and actual survival through Kaplan-Meier analyses.RESULTS We included 397 patients who were first diagnosed with PBC during hospitalization and received UDCA treatment;most disease stages were advanced.After an average of 6.4±1.4 years of follow-up,82 patients had died,and 4 patients had undergone LT.After receiving UDCA treatment for 1 year,the score with the best discrimination performance was the Mayo,with a concordance statistic of 0.740(95%confidence interval:0.690-0.791).The albumin-bilirubin,GLOBE,and Mayo scores tended to overestimate transplant-free survival.Comparing 7 years of calibration results showed that the Mayo score was the best model.CONCLUSION The Mayo,GLOBE,UK-PBC,and ALBI scores demonstrated comparable discriminating performance for advanced stage PBC.The Mayo score showed optimal discriminatory performance and excellent predictive accuracy.