Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

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.

Acute suppurative terminal cholangitis:Clinical characteristics of a new subtype of acute cholangitis

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.

MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation

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.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

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.

Response letter to “Acute cholangitis: Does malignant biliary obstruction vs choledocholithiasis etiology change the outcomes?” with imaging aspects

Radiological imaging findings may contribute to the differentiation of malignant biliary obstruction from choledocholithiasis in the etiology of acute cholangitis.

Cryptococcus splenic abscess in primary biliary cholangitis: a case report

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.

Urgent one-stage endoscopic treatment for choledocholithiasis related moderate to severe acute cholangitis: A propensity scorematched analysis

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.

Red cell distribution width-to-albumin ratio is a simple promising prognostic marker in acute cholangitis requiring biliary drainage

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.

Study on the effect and mechanism of Swertia mussotii Franch. in the treatment of primary biliary cholangitis based on bioinformatics and in vitro experiments

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.

Acute cholangitis with Achromobacter xylosoxidans bacteremia after endoscopic retrograde cholangiopancreatography in hilar cholangiocarcinoma:A case report

BACKGROUND Achromobacter xylosoxidans is a Gram-negative opportunistic aerobe,usually causing nosocomial infections in immunocompromised patients with manifestations including bacteremia,pneumonia,and catheter-related infections.However,A.xylosoxidans have not yet been reported to cause biliary system infections.CASE SUMMARY A 72-year-old woman presented to the outpatient department of our hospital with a chief complaint of jaundice.Computed tomography of her abdomen revealed the presence of a mass of approximately 2.4 cm in the hilar portion of the common hepatic duct,consistent with hilar cholangiocarcinoma.We performed endoscopic retrograde cholangiopancreatography(ERCP)to decompress the obstructed left and right intrahepatic ducts(IHDs)and placed 10 cm and 11 cm biliary stents in the left and right IHDs,respectively.However,the day after the procedure,the patient developed post-ERCP cholangitis as the length of the right IHD stent was insufficient for proper bile drainage.The blood culture of the patient tested positive for A.xylosoxidans.Management measures included the replacement of the right IHD stent(11 cm)with a longer one(12 cm)and administering culturedirected antibiotic therapy,solving the cholangitis-related complications.After the cholangitis had resolved,the patient underwent surgery for hilar cholangiocarcinoma and survived for 912 d without recurrence.CONCLUSION A.xylosoxidans-induced biliary system infections are extremely rare.Clinical awareness of physicians and endoscopists is required as this rare pathogen might cause infection after endoscopic procedures.

Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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.

Functional investigation and two-sample Mendelian randomization study of primary biliary cholangitis hub genes

BACKGROUND The identification of specific gene expression patterns is crucial for understanding the mechanisms underlying primary biliary cholangitis(PBC)and finding relevant biomarkers for diagnosis and therapeutic evaluation.AIM To determine PBC-associated hub genes and assess their clinical utility for disease prediction.METHODS PBC expression data were obtained from the Gene Expression Omnibus database.Overlapping genes from differential expression analysis and weighted gene coexpression network analysis(WGCNA)were identified as key genes for PBC.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were performed to explore the potential roles of key genes.Hub genes were identified in protein-protein interaction(PPI)networks using the Degree algorithm in Cytoscape software.The relationship between hub genes and immune cells was investigated.Finally,a Mendelian randomization study was conducted to determine the causal effects of hub genes on PBC.RESULTS We identified 71 overlapping key genes using differential expression analysis and WGCNA.These genes were primarily enriched in pathways related to cytokinecytokine receptor interaction,and Th1,Th2,and Th17 cell differentiation.We utilized Cytoscape software and identified five hub genes(CD247,IL10,CCL5,CCL3,and STAT3)in PPI networks.These hub genes showed a strong correlation with immune cell infiltration in PBC.However,inverse variance weighting analysis did not indicate the causal effects of hub genes on PBC risk.CONCLUSION Hub genes can potentially serve as valuable biomarkers for PBC prediction and treatment,thereby offering significant clinical utility.

IgG4-related sclerosing cholangitis associated with essential thrombocythemia:A case report

BACKGROUND The complexity of immunoglobulin G4(IgG4)-related diseases and their potential connection to hematologic malignancies remains unclear.This article provided a review of the diagnosis and treatment of a patient with IgG4-related sclerosing cholangitis(SC)and essential thrombocythemia(ET),along with an analysis of relevant literature to enhance comprehension of this disease.CASE SUMMARY A 56-year-old male was admitted to two hospitals with deteriorating jaundice and pruritus prior to hospitalization.Beyond our expectations,the patient was first diagnosed with IgG4-SC and ET with the Janus kinase 2 V617F mutation.Interestingly,the administration of acetate prednisone significantly resulted in improvements in both IgG4-SC and ET.Clinicians need to pay attention to immune disorders and inflammation as they contribute to the development of various disease phenotypes.CONCLUSION When IgG4-SC is suspected without histopathological evidence,diagnostic therapy and long-term regular follow-up can lead to positive treatment outcomes.Clinicians should be mindful of the potential presence of concurrent hematologic diseases in patients with immune disorders.

Journey to diagnosis:An unfinished exploration of IgG4-related sclerosing cholangitis

IgG4-related sclerosing cholangitis(IgG4-SC)is an inflammatory disease that leads to bile duct stricture,characterized by the infiltration of IgG4-positive plasma cells into the bile duct wall,thickening of the bile duct wall,and narrowing of the lumen.The differential diagnosis of IgG4-SC mainly includes primary sclerosing cholangitis,cholangiocarcinoma,and pancreatic cancer.IgG4-SC is often associated with autoimmune pancreatitis and can be accurately diagnosed based on clinical diagnostic criteria.However,isolated IgG4-SC is difficult to distinguish from biliary tumors.Given the significant differences in biological behavior,treatment,and prognosis between these diseases,accurately identifying isolated IgG4-SC has very important clinical significance.

Impact of index admission cholecystectomy vs interval cholecystectomy on readmission rate in acute cholangitis: National Readmission Database survey

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.

Clinicopathological features of 11 cases of chronic hepatitis B infection complicated with primary biliary cholangitis

BACKGROUND Only a few cases of chronic hepatitis B(CHB)with primary biliary cholangitis(PBC)have been reported based on histological evidence from liver biopsies.AIM To observe the clinicopathological features and outcomes of 11 patients with CHB infection complicated by PBC.METHODS Eleven patients with CHB and PBC who underwent liver biopsy at the Zhenjiang Third Hospital,affiliated with Jiangsu University,and Wuxi Fifth People’s Hospital,from January 2005 to September 2020,were selected.All patients initially visited our hospital with CHB and were pathologically diagnosed with CHB and PBC.RESULTS Only five had elevated alkaline phosphatase levels,nine were positive for antimitochondrial antibody(AMA)-M2,and two were negative for AMA-M2.Two had jaundice and pruritus symptoms,10 had mildly abnormal liver function,and one had severely elevated bilirubin and liver enzyme levels.The pathological characteristics of CHB complicated by PBC overlapped with those of PBCautoimmune hepatitis(AIH).When necroinflammation of the portal area is not obvious,the pathological features of PBC are predominant,similar to the features of PBC alone.When the interface is severe,biliangitis will occur,with a large number of ductular reactions in zone 3.Unlike the PBC-AIH overlap pathology,this pathology is characterized by a small amount of plasma cell infiltration.Unlike PBC,lobulitis is often observed.CONCLUSION This is the first large case series to show that the rare pathological features of CHB with PBC are similar to those of PBC-AIH and small duct injury was observed.

Pathogenesis of primary biliary cholangitis

Disease overview of primary biliary cholangitis(PBC).PBC is one of the main subgroups of chronic cholestatic liver disease.In 2015,the designation of PBC was changed from primary biliary cirrhosis to remove the“cirrhosis stigma”to more accurately reflect the disease and its natural course[1,2].PBC is a chronic cholestasis disease mediated by autoimmunity.

Short vs long-course antibiotic therapy in adults with acute cholangitis:A systematic review,meta-analysis,and evidence quality assessment

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.

Predictive value of presepsin and acylcarnitines for severity and biliary drainage in acute cholangitis

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.

Prognostic scores in primary biliary cholangitis patients with advanced disease

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.