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.

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.

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.

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.

Limited validity of Mayo endoscopic subscore in ulcerative colitis with concomitant primary sclerosing cholangitis

BACKGROUND Ulcerative colitis(UC)with concomitant primary sclerosing cholangitis(PSC)represents a distinct disease entity(PSC-UC).Mayo endoscopic subscore(MES)is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear.AIM To assess the accuracy of MES in UC and PSC-UC patients,we performed histological scoring using Nancy histological index(NHI).METHODS MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy.NHI and inflammation were evaluated in biopsies from the cecum,rectum,and terminal ileum.In addition,perinuclear anti-neutrophil cytoplasmic antibodies,fecal calprotectin,body mass index,and other relevant clinical characteristics were collected.RESULTS The median MES and NHI were similar for UC patients(MES grade 2 and NHI grade 2 in the rectum)but were different for PSC-UC patients(MES grade 0 and NHI grade 2 in the cecum).There was a correlation between MES and NHI for UC patients(Spearman's r=0.40,P=0.029)but not for PSC-UC patients.Histopathological examination revealed persistent microscopic inflammation in 88%of PSC-UC patients with MES grade 0(46%of all PSC-UC patients).Moreover,MES overestimated the severity of active inflammation in an additional 11%of PSCUC patients.CONCLUSION MES insufficiently identifies microscopic inflammation in PSC-UC.This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.

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.

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.

Diagnosis of IgG4-related sclerosing cholangitis

IgG4-related sclerosing cholangitis(IgG4-SC)is often associated with autoimmune pancreatitis.However,the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis(PSC),and the presence of segmental stenosis suggests cholangiocarcinoma(CC).IgG4-SC responds well to steroid therapy,whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention.Since IgG4-SC was first described,it has become a third distinct clinical entity of sclerosing cholangitis.The aim of this review was to introduce the diagnostic methods for IgG4-SC.IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical,serological,morphological,and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis.When intrapancreatic stenosis is detected,pancreatic cancer or CC should be ruled out.If multiple intrahepatic stenoses are evident,PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining.Associated inflammatory bowel disease is suggestive of PSC.If stenosis is demonstrated in the hepatic hilar region,CC should be discriminated by ultrasonography,intraductal ultrasonography,bile duct biopsy,and a higher cutoff serum IgG4 level of 182 mg/dL.

Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis

AIM:To review the current literature for the specificclinical characteristics of inflammatory bowel disease(IBD)associated with primary sclerosing cholangitis(PSC).METHODS:A systematical review for clinical characteristics of IBD in PSC was performed by conducting a broad search for"primary sclerosing cholangitis"in Pubmed."Clinical characteristics"were specified into five predefined subthemes:epidemiology of IBD in PSC,characteristics of IBD in PSC(i.e.,location,disease behavior),risk of colorectal cancer development,IBD recurrence and de novo disease after liver transplantation for PSC,and safety and complications after proctocolectomy with ileal pouchanal anastomosis.Papers were selected for inclusion based on their relevance to the subthemes,and were reviewed by two independent reviewers.Only full papers relevant to PSC-IBD were included.Additionally the references of recent reviews for PSC(<5 years old)were scrutinized for relevant articles.RESULTS:Initial literature search for PSC yielded 4704results.After careful review 65 papers,comprising a total of 11406 PSC-IBD patients,were selected and divided according to subtheme.Four manuscripts overlapped and were included in two subthemes.Prevalence of IBD in PSC shows a large variance,ranging from 46.5%to 98.7%with ulcerative colitis(UC)being the most common type(>75%).The highest IBD rates in PSC are found in papers reviewing both endoscopic and histological data for IBD diagnosis.Although IBD in PSC is found to be a quiescent disease,pancolitis occurs often,with rates varying from 35%to 95%.Both backwash ileitis and rectal sparing are observed infrequently.The development of dysplasia or colorectal carcinoma is increased in PSC-IBD;the cumulative 10 years risk varying between 0%and11%.Exacerbation of IBD is common after liver transplantation for PSC and de novo disease is seen in1.3%to 31.3%of PSC-IBD patients.The risk for development of pouchitis in PSC-IBD is found to besignificant,affecting 13.8%to 90%of the patients after proctocolectomy with ileo anal-pouch anastomosis.CONCLUSION:IBD in primary sclerosing cholangitis represents a distinct phenotype that differs from UC and Crohn’s disease and therefore requires specialized management.

Inflammatory bowel disease of primary sclerosing cholangitis:A distinct entity?

This is a review of the characteristic findings of inflammatory bowel disease(IBD)associated with primary sclerosing cholangitis(PSC)and their usefulness in the diagnosis of sclerosing cholangitis.PSC is a chronic inflammatory disease characterized by idiopathic fibrous obstruction and is frequently associated with IBD.IBDassociated with PSC(PSC-IBD)shows an increased incidence of pancolitis,mild symptoms,and colorectal malignancy.Although an increased incidence of pancolitis is a characteristic finding,some cases are endoscopically diagnosed as right-sided ulcerative colitis.Pathological studies have revealed that inflammation occurs more frequently in the right colon than the left colon.The frequency of rectal sparing and backwash ileitis should be investigated in a future study based on the same definition.The cholangiographic findings of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)are similar to those of PSC.The rare association between IBD and IgG4-SC and the unique characteristics of PSC-IBD are useful findings for distinguishing PSC from IgG4-SC.

Diagnostic value of elevated serum carbohydrate antigen 199 level in acute cholangitis secondary to choledocholithiasis

AIM To investigate the diagnostic value of abnormal serum carbohydrate antigen 199(CA199) level in acute cholangitis secondary to choledocholithiasis.METHODS In this retrospective cohort study, the clinical data of 727 patients with choledocholithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from June 2011 to June 2017 were collected. Among these patients, 258 patients had secondary acute cholangitis and served as observation group, and the remaining 569 choledocholithiasis patients served as the control group. Serum liver function indexes and tumor markers were detected in both groups, and the receiver operating characteristic(ROC) curves were constructed for markers showing statistical significances. The cutoff value, sensitivity, and specificity of each marker were calculated according to the ROC curves. RESULTS The results of liver function tests showed no significant differences between the two groups(P > 0.05). Tumor markers including serum CA125, CA153, carcinoembryonic antigen, and alpha fetoprotein levels were also not significantly different(P > 0.05); however, the serum CA199 level was significantly higher in the observation group than in the control group(P < 0.05). The ROC curve analysis showed that the area under the curve was 0.885(95%CI: 0.841-0.929) for CA199, and the cutoff value of 52.5 kU/L had the highest diagnostic accuracy, with a sensitivity of 86.8% and a specificity of 81.6%.CONCLUSION Abnormally elevated serum CA199 level has an important value in the diagnosis of acute cholangitis secondary to choledocholithiasis. It may be a specific inflammatory marker for acute cholangitis.

Safety of immediate endoscopic sphincterotomy in acutesuppurative cholangitis caused by choledocholithiasis

AIM: To examine the safety of immediate endoscopic sphincterotomy(EST) in patients with acute suppurative cholangitis(ASC) caused by choledocholithiasis, as compared with elective EST.METHODS: Patients with ASC due to choledocholithiasis were allocated to two groups: Those who underwent EST immediately and those who underwent EBD followed by EST 1 wk later because they were under anticoagulant therapy, had a coagulopathy(international normalized ratio > 1.3, partial thromboplastin time greater than twice that of control), or had a platelet count < 50000 × 103/μL. One of four trainees [200-400 cases of endoscopic retrograde cholangiopancreatography(ERCP)] supervised by a specialist(> 10000 cases of ERCP) performed the procedures. The success and complication rates associated with EST in each group were examined.RESULTS: Of the 87 patients with ASC, 59 were in the immediate EST group and 28 in the elective EST group. EST was successful in all patients in both groups. There were no complications associated with EST in either group of patients, although white blood cell count, C-reactiveprotein, total bilirubin, and serum concentrations of liver enzymes just before EST were significantly higher in the immediate EST group than in the elective EST group.CONCLUSION: Immediate EST can be as safe as elective EST for patients with ASC associated with choledocholithiasis provided they are not under anticoagulant therapy, or do not have a coagulopathy or a platelet count < 50000 × 103/μL. Moreover, the procedure was safely performed by a trainee under the supervision of an experienced specialist.

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.

Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: A review of the literature

To examine and evaluate recent evidence regarding the epidemiology, pathogenesis and management of colorectal cancer(CRC) development in inflammatory bowel disease(IBD)-primary sclerosing cholangitis(PSC) patients. Using the PubMed database, a literature search was conducted for relevant articles in English from the past 10 years. Relevant studies investigating PSC as a risk factor for CRC in IBD in the context of incidence and prevalence, pathogenesis, prevention and prognosis were included in this review. Recent evidence increasingly points to PSC as a significant risk factor in the development of CRC in patients with concomitant IBD. PSC may be an important risk factor for CRC in different populations worldwide. The mechanism for this increase in risk is still unclear. The efficacy of UDCA as a chemopreventive agent remains controversial. Liver transplantation does not halt the development of CRC, although there is not enough evidence to suggest that it is associated with increased incidence of CRC. While routine colonoscopic surveillance should be performed in patients with concurrent PSC and IBD, more high-level evidence is required to support the benefits of the procedure. While many new developments have taken place in the last decade, the pathogenesis and optimal management of CRC development in IBD-PSC patients remain unclear.

Factors predicting adverse short-term outcomes in patients with acute cholangitis undergoing ERCP: A single center experience

AIM: To identify potential factors that can predict adverse short-term outcomes in patients with acute cholangitis undergoing endoscopic retrograde cholangiopancreatography(ERCP). METHODS: Retrospective analysis of consecutive patients admitted to our center for acute cholangitis and underwent ERCP from 2001 to 2012. Involvement of two or more organ systems was termed as organ failure(OF). Cardiovascular failure was defined based on a systolic blood pressure of < 90 mmHg despite fluid replacement and/or requiring vasopressor treatment; respiratory failure if the Pa02 /Fi02 ratio was < 300 mmHg and/or required mechanical ventilation; coagulopathy if the platelet count was < 80; and renal insufficiency if serum creatinine was > 1.9 mg/dL. Variables associated with short term adverse clinical outcomes defined as persistent OF and/or 30-d mortality was determined. RESULTS: A total of 172 patients(median age 62 years, 56.4% female) were included. The median door to ERCP time was 17 h. Bile duct stones were the most common etiology(n = 67, 39.2%). In multivariate analysis, factors that were independently associated with persistent OF and/or 30-d mortality included American Society of Anesthesiology(ASA) physical classification score > 3(OR = 7.70; 95%CI: 2.73-24.40), presence of systemic inflammatory response syndrome(OR = 3.67; 95%CI: 1.34-10.3) and door to ERCP time greater than 72 h(OR = 3.36; 95%CI: 1.12-10.20). Door to ERCP time greater than 72 h was also associated with 70% increase in the mean length of stay(P < 0.001). Every one point increase in the ASA physical classification and every 1 mg/dL increase in the preERCP bilirubin level was associated with a 34% and 2% increase in the mean length of hospital stay, respectively. Transfer status did not impact clinical outcomes. CONCLUSION: Higher ASA physical classification and delays in ERCP are associated with adverse clinical outcomes and prolonged length of hospital stay in patients with acute cholangitis undergoing ERCP.

Update on inflammatory bowel disease in patients with primary sclerosing cholangitis

Patients with primary sclerosing cholangitis(PSC) complicated by inflammatory bowel disease(IBD) represent a distinct subset of patients with unique characteristics,which have serious clinical implications.The aim of this literature review was to shed light to the obscure clinical and molecular aspects of the two diseases combined utilizing current data available and putting issues of diagnosis and treatment into perspective.The prevalence of IBD,mainly ulcerative colitis in PSC patients is estimated to be 21%-80%,dependent on screening programs and nationality.PSC-associated colitis is likely to be extensive,characterized by rectal sparing,backwash ileitis,and generally mild symptoms.It is also more likely to progress to colorectal malignancy,making it imperative for clinicians to maintain a high level of suspicion when tackling PSC patients.There is no optimal surveillance strategy but current guidelines advocate that colonoscopy is necessary at the time of PSC diagnosis with annual endoscopic follow-up.Random biopsies have been criticized and a shift towards targeted biopsies using chromoendoscopy,laser endomicroscopy and narrow-band imaging has been noted.Techniques directed towards genetic mutations instead of histological abnormalities hold promise for easier,more accurate diagnosis of dysplastic lesions.Chemopreventive measures against colorectal cancer have been sought in these patients.Ursodeoxycholic acid seemed promising at first but subsequent studies yielded conflicting results showing anticarcinogenic effects in low doses(8-15 mg/kg per day) and carcinogenic properties in high doses(15-30 mg/kg per day).

Endoscopic sphincterotomy associated cholangitis in patients receiving proximal biliary self-expanding metal stents

BACKGROUND: Endoscopic biliary stent placement during the procedure of endoscopic retrograde cholangiopancreatography (ERCP) is preferred to provide biliary drainage for unresectable malignant biliary obstruction. There is considerable controversy over the use of endoscopic sphincterotomy (ES) prior to stent placement. This study aimed to determine whether ES before intraductal self-expanding metal stent (SEMS) placement affects the clinical outcome and complications in patients with proximal malignant obstructive biliary diseases. METHODS: In a prospective randomized controlled trial, 82 patients with inoperable malignant biliary strictures were randomly assigned to biliary stenting groups with or without ES. Resolution of jaundice and the incidence of complications including acute cholangitis, pancreatitis and stent occlusion within 6 months were evaluated. RESULTS: SEMSs were successfully deployed in all patients, resulting in clinical and biochemical improvement of obstructive symptoms in both groups. The incidence of cholangitis was higher in the ES group than in the non-ES group (58.5% vs 31.7%, P=0.015). The interval between stent placement and the first acute cholangitis was much shorter in the ES group than in the non-ES group (P=0.024). The use of ES increased the incidence of cholangitis (P=0.004, risk ratio, 8.196). The rate of post-ERCP pancreatitis after stent placement was greater in the non-ES group than in the ES group (31.7% vs 9.8%, P=0.014). No significant differences were found in the rate of restenosis and the mortality rate between the two groups.CONCLUSIONS: ES prior to intraductal SEMS placement was associated with an increased incidence of acute cholangitis. ES should be carefully evaluated prior to its use in patients with proximal malignant obstructive biliary diseases.

Sclerosing cholangitis secondary to bleomycin-iodinated embolization for liver hemangioma

Sclerosing cholangitis(SC)is a rarely reported morbidity secondary to transcatheter arterial chemoembolization(TACE)with bleomycin-iodinated oil(BIO)for liver cavernous hemangioma(LCH).This report retrospectively evaluated the diagnostic and therapeutic course of a patient with LDH who presented obstructive jaundice 6 years after TACE with BIO.Preoperative imaging identified a suspected malignant biliary stricture located at the convergence of the left and right hepatic ducts.Operative exploration demonstrated a full-thickness sclerosis of the hilar bile duct with right hepatic duct stricture and right lobe atrophy.Radical hepatic hilar resection with right-side hemihepatectomy and Roux-en-Y hepaticojejunostomy was performed because hilar cancer could not be excluded on frozen biopsy.Pathological results showed chronic pyogenic inflammation of the common and right hepatic ducts with SC in the portal area.Secondary SC is a long-term complication that may occur in LCH patients after TACE with BIO and must be differentiated from hilar malignancy.Hepatic duct plasty is a definitive but technically challenging treatment modality for secondary SC.

Diagnostic challenges of Wilson’s disease presenting as acute pancreatitis, cholangitis, and jaundice

Wilson’s disease is a rare disorder of copper transport in hepatic cells,and may present as cholestatic liver disease;pancreatitis and cholangitis are rarely associated with Wilsons’s disease.Moreover,cases of Wilson s disease presenting as pigmented gallstone pancreatitis have not been reported in the literature.In the present report,we describe a case of a 37-year-old man who was admitted with jaundice and abdomina pain.The patient was diagnosed with acute pancreatitis,cholangitis,and obstructive jaundice caused by pigmented gallstones that were detected during retrograde cholangiopancreatography.However,because of his long-term jaundice and the presence of pigmented gallstones,the patient underwent further evaluation for Wilson’s disease,which was subsequently confirmed.This patient’s unique presentation exemplifies the overlap in the clinical and laboratory parameters of Wilson’s disease and cholestasis,and the difficulties associated with their differentiation.It suggests thatWilson’s disease should be considered in patients with pancreatitis,cholangitis,and severe protracted jaundice caused by pigmented gallstones.