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 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 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 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 patie...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.展开更多
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 bu...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.展开更多
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 d...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.展开更多
In our case, we present a case of an 80-year-old male who was referred to the gastroenterologist for evaluation of a suspicious mass. CT imaging at the time had shown intrahepatic and extrahepatic biliary dilations, a...In our case, we present a case of an 80-year-old male who was referred to the gastroenterologist for evaluation of a suspicious mass. CT imaging at the time had shown intrahepatic and extrahepatic biliary dilations, and the patient was thought to have a pancreatic or a common bile duct mass. A mass biopsy showed no malignancy, and further evaluation was warranted. The patient was found to have elevated IgG4 levels and was diagnosed with IgG4-sclerosing cholangitis (IgG4-SC). IgG4 has been found to create a wide array of pathologies, including autoimmune pancreatitis, dacryoadenitis, and sialadenitis. These pathologies have been grouped under an IgG4-Related Disease (IgG4-RD) category. In some cases, this IgG4-RD can present as a subclass of primary sclerosing cholangitis due to immune depositions and swelling of the CBD. Due to the strictures caused by the sclerosing cholangitis, intrahepatic and extrahepatic dilations might be found on endoscopic ultrasound (EUS). It is imperative to differentiate this from a malignant mass as the early recognition and treatment of IgG4-SC can lead to complete resolution. In this case report, we present a case of a patient who was found to have IgG4-SC and responded well to steroid treatment.展开更多
Primary sclerosing cholangitis(PSC)is a chronic and progressive immunemediated cholangiopathy causing biliary tree inflammation and scarring,leading to liver cirrhosis and end-stage liver disease.Diagnosis of PSC is c...Primary sclerosing cholangitis(PSC)is a chronic and progressive immunemediated cholangiopathy causing biliary tree inflammation and scarring,leading to liver cirrhosis and end-stage liver disease.Diagnosis of PSC is challenging due to its nonspecific symptoms and overlap with other liver diseases.Despite the rising incidence of PSC,there is no proven medical therapy that can alter the natural history of the disease.While liver transplantation(LT)is the most effective approach for managing advanced liver disease caused by PSC,post-transplantation recurrence of PSC remains a challenge.Therefore,ongoing research aims to develop better therapies for PSC,and continued efforts are necessary to improve outcomes for patients with PSC.This article provides an overview of PSC’s pathogenesis,clinical presentation,and management options,including LT trends and future aspects.It also highlights the need for improved therapeutic options and ethical considerations in providing equitable access to LT for patients with PSC.Additionally,the impact of liver transplant on the quality of life and psychological outcomes of patients with PSC is discussed.Ongoing research into PSC’s pathogenesis and post-transplant recurrence is crucial for improved understanding of the disease and more effective treatment options.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 Primary sclerosing cholangitis(PSC)is an extraintestinal manifestation of ulcerative colitis(UC).PSC is a well-known risk factor for intrahepatic cholangiocarcinoma(ICC),and ICC is known to have a poor prog...BACKGROUND Primary sclerosing cholangitis(PSC)is an extraintestinal manifestation of ulcerative colitis(UC).PSC is a well-known risk factor for intrahepatic cholangiocarcinoma(ICC),and ICC is known to have a poor prognosis.CASE SUMMARY We present two cases of ICC in patients with PSC associated with UC.In the first case,a tumor was found by magnetic resonance imaging(MRI)in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain.The second patient was asymptomatic,but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC.ICC was strongly suspected by computed tomography and MRI in both cases,and surgery was performed,but unfortunately,the first patient died of ICC recurrence 16 mo postoperatively,and the second patient died of liver failure 14 mo postoperatively.CONCLUSION Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.展开更多
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 inf...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.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 a chronic cholestatic syndrome of unknown origin mostly found in males, and characterized by diffuse inflammation and fibrosis of both intra- and extra-hepatic bile ducts. So fa...Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown origin mostly found in males, and characterized by diffuse inflammation and fibrosis of both intra- and extra-hepatic bile ducts. So far, PSC is considered as an autoimmune hepatobiliary disease. In most cases the progression of PSC towards liver cirrhosis and liver failure is slow but irreversible, and liver transplantation is currently the only definitive treatment. In recent years,PSC has been an area of active research worldwide with great interest in etiology, pathogenesis, diagnosis, and therapeutic options such as hydrophilic ursodeoxycholic acid and immunosuppressive agent tacrolimus. Recent updates on clinical and therapeutic aspects of PSC are discussed in the present review.展开更多
Primary sclerosing cholangitis(PSC)is an autoimmune disease characterized by chronic cholestasis,a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis.Gut microbes,consisting of...Primary sclerosing cholangitis(PSC)is an autoimmune disease characterized by chronic cholestasis,a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis.Gut microbes,consisting of microorganisms colonized in the human gut,play an important role in nutrient intake,metabolic homeostasis,immune regulation,and immune regulation;however,their presence might aid PSC development.Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC.Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria.Dysbiosis of the intestinal flora leads to increased intestinal permeability,homing of intestinal lymphocytes,entry of bacteria and their associated metabolites,such as bile acids,into the liver,stimulation of hepatic immune activation,and promotion of PSC.Currently,PSC effective treatment is lacking.However,a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases(alcoholic liver disease,metabolic fatty liver,cirrhosis,and autoimmune liver disease).In addition,antibiotics,fecal microbiota transplantation,and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis,suggesting their effectiveness for PSC treatment.Therefore,this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.展开更多
Primary sclerosing cholangitis(PSC) is a chronic,cholestatic liver condition characterized by inflammation,fibrosis,and destruction of the intra-and extrahepatic bile ducts.The therapeutic endoscopist plays a key role...Primary sclerosing cholangitis(PSC) is a chronic,cholestatic liver condition characterized by inflammation,fibrosis,and destruction of the intra-and extrahepatic bile ducts.The therapeutic endoscopist plays a key role in the diagnosis and management of PSC.In patients presenting with a cholestatic profile,endoscopic retrograde cholangiopancreatography(ERCP) is warranted for a definite diagnosis of PSC.Dominant strictures of the bile duct occur in 36%-57% of PSC patients.Endoscopic balloon dilatation with or without stenting have been employed in the management of dominant strictures.In addition,PSC patients are at increased risk of developing cholangiocarcinoma with a 20% lifetime risk.Brush cytology obtained during ERCP and use of fluorescence in situ hybridization forms the initial diagnostic step in the investigation of patients with dominant biliary strictures.Our review aims to summarize the current evidence supporting the role of a therapeutic endoscopist in the management of PSC patients.展开更多
BACKGROUND A type 2b immunoglobulin G4(IgG4)-related sclerosing cholangitis(SC)without autoimmune pancreatitis is a rare condition with IgG4-SC.While the variety of the imaging modalities have tested its usefulness in...BACKGROUND A type 2b immunoglobulin G4(IgG4)-related sclerosing cholangitis(SC)without autoimmune pancreatitis is a rare condition with IgG4-SC.While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC,however,the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition.Therefore,the information of our recent case and reported cases have been summarized.CASE SUMMARY We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4,narrowing of the bile duct,its wall thickness,no complication of autoimmune pancreatitis,and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes.The cholangiogram revealed type 2b according to the classification.Corticosteroid treatment showed a favorable effect,with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness.CONCLUSION As isolated type 2b,IgG4-SC is rare,the images,histological findings,and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.展开更多
MM: Persistent cholestasis is a rare complication of severe trauma or infections. Little is known about the possible pathomechanisms and the clinical course.METHODS: Secondary sclerosing cholangitis was diagnosed in...MM: Persistent cholestasis is a rare complication of severe trauma or infections. Little is known about the possible pathomechanisms and the clinical course.METHODS: Secondary sclerosing cholangitis was diagnosed in five patients with persistent jaundice after severe trauma (one burn injury, three accidents, one power current injury). Medical charts were retrospectively reviewed with regard to possible trigger mechanisms for cholestasis, and the clinical course was recorded.RESULTS: Diagnosis of secondary sclerosing cholangitis was based in all patients on the primary sclerosing cholangitis (PSC)-Iike destruction of the intrahepatic bile ducts at cholangiography after exclusion of PSC. In four patients, arterial hypotension with subsequent ischemia may have caused the bile duct damage, whereas in the case of power current injury direct thermal damage was assumed to be the trigger mechanism. The course of secondary liver fibrosis was rapidly progressive and proceeded to liver cirrhosis in all four patients with a follow-up 〉2 years. Therapeutic possibilities were limited.CONCLUSION: Posttraumatic sderosing cholangitis is a rare but rapidly progressive disease, probably caused by ischemia of the intrahepatic bile ducts via the peribiliary capillary plexus due to arterial hypotension.Gastroenterologists should be aware of this disease in patients with persistent cholestasis after severe trauma.展开更多
AIM:To clarify the characteristic features of biliary le-sions in patients with autoimmune pancreatitis(AIP) and compare them with those of primary sclerosing cholangitis(PSC) .METHODS:The clinicopathological characte...AIM:To clarify the characteristic features of biliary le-sions in patients with autoimmune pancreatitis(AIP) and compare them with those of primary sclerosing cholangitis(PSC) .METHODS:The clinicopathological characteristics of 34 patients with sclerosing cholangitis(SC) associated with AIP were compared with those of 4 patients with PSC.RESULTS:SC with AIP occurred predominantly in el-derly men.Obstructive jaundice was the most frequent initial symptom in SC with AIP.Only SC patients with AIP had elevated serum IgG4 levels,and sclerosing diseases were more frequent in these patients.SC pa-tients with AIP responded well to steroid therapy.Seg-mental stenosis of the lower bile duct was observed only in SC patients with AIP,but a beaded and pruned-tree appearance was detected only in PSC patients.Dense infi ltration of IgG4-positive plasma cells was de-tected in the bile duct wall and the periportal area,as well as in the pancreas,of SC patients with AIP.CONCLUSION:SC with AIP is distinctly different from PSC.The two diseases can be discriminated based on cholangiopancreatographic findings and serum IgG4 levels.展开更多
To our knowledge,patients with immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)associated with autoimmune hemolytic anemia(AIHA)have not been reported previously.Many patients with IgG4-SC have autoimmune pan...To our knowledge,patients with immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)associated with autoimmune hemolytic anemia(AIHA)have not been reported previously.Many patients with IgG4-SC have autoimmune pancreatitis(AIP)and respond to steroid treatment.However,isolated cases of IgG4-SC are difficult to diagnose.We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis.The patient was a73-year-old man who was being treated for dementia.Liver dysfunction was diagnosed on blood tests at another hospital.Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis,but a rapidly progressing anemia developed simultaneously.After the diagnosis of AIHA,steroid treatment was begun,and the biliary stricture improved.IgG4-SC without AIP was thus diagnosed.展开更多
Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis,except epidemic schistosomiasis.Among them,primary sclerosing cholangitis (PSC) might initiate...Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis,except epidemic schistosomiasis.Among them,primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues,giving rise to systemic amyloidosis,due to a progressive and unresolved inflammatory process,and its possible association with inflammatory bowel diseases.Nevertheless,only one such case has been reported in the literature to date.We report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis,without any evidence of other inflammatory disorders.As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4,the presence of IgG4 + plasma cells was examined systemically,resulting in unexpected documentation of Congo-red-positive amyloid deposits,but not IgG4 + plasma cells,in the liver,stomach and salivary glands.Elevated serum IgG4 is the hallmark of IgG4-related disease,including IgG4-associated cholangitis,but it has also been demonstrated in certain patients with PSC.Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.展开更多
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.
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.
基金Natural Science Foundation of Hebei Province,No.H2023206042。
文摘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.
基金Supported by Grant Agency of the Ministry of Health of the Czech Republic,No.NV17-31538AGrant Agency of the Czech Republic No.20-16520Y and No.21-21736SMinistry of Education,Youth and Sports of the Czech Republic Project,No.LX22NPO05102.
文摘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.
基金Supported by The Science and Technology Research Foundation of Guizhou Province,and Zunyi City,No.QKHJC-ZK(2022)YB642,No.ZSKH·HZ(2022)344,and No.gzwjkj2021-071The WBE Liver Fibrosis Foundation,No.CFHPC2025028The Beijing Gandan Phase Mutual Public Welfare Fund for Artificial Liver Project,No.iGandanF-1082024-Rgg018.
文摘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.
文摘In our case, we present a case of an 80-year-old male who was referred to the gastroenterologist for evaluation of a suspicious mass. CT imaging at the time had shown intrahepatic and extrahepatic biliary dilations, and the patient was thought to have a pancreatic or a common bile duct mass. A mass biopsy showed no malignancy, and further evaluation was warranted. The patient was found to have elevated IgG4 levels and was diagnosed with IgG4-sclerosing cholangitis (IgG4-SC). IgG4 has been found to create a wide array of pathologies, including autoimmune pancreatitis, dacryoadenitis, and sialadenitis. These pathologies have been grouped under an IgG4-Related Disease (IgG4-RD) category. In some cases, this IgG4-RD can present as a subclass of primary sclerosing cholangitis due to immune depositions and swelling of the CBD. Due to the strictures caused by the sclerosing cholangitis, intrahepatic and extrahepatic dilations might be found on endoscopic ultrasound (EUS). It is imperative to differentiate this from a malignant mass as the early recognition and treatment of IgG4-SC can lead to complete resolution. In this case report, we present a case of a patient who was found to have IgG4-SC and responded well to steroid treatment.
文摘Primary sclerosing cholangitis(PSC)is a chronic and progressive immunemediated cholangiopathy causing biliary tree inflammation and scarring,leading to liver cirrhosis and end-stage liver disease.Diagnosis of PSC is challenging due to its nonspecific symptoms and overlap with other liver diseases.Despite the rising incidence of PSC,there is no proven medical therapy that can alter the natural history of the disease.While liver transplantation(LT)is the most effective approach for managing advanced liver disease caused by PSC,post-transplantation recurrence of PSC remains a challenge.Therefore,ongoing research aims to develop better therapies for PSC,and continued efforts are necessary to improve outcomes for patients with PSC.This article provides an overview of PSC’s pathogenesis,clinical presentation,and management options,including LT trends and future aspects.It also highlights the need for improved therapeutic options and ethical considerations in providing equitable access to LT for patients with PSC.Additionally,the impact of liver transplant on the quality of life and psychological outcomes of patients with PSC is discussed.Ongoing research into PSC’s pathogenesis and post-transplant recurrence is crucial for improved understanding of the disease and more effective treatment options.
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.
文摘BACKGROUND Primary sclerosing cholangitis(PSC)is an extraintestinal manifestation of ulcerative colitis(UC).PSC is a well-known risk factor for intrahepatic cholangiocarcinoma(ICC),and ICC is known to have a poor prognosis.CASE SUMMARY We present two cases of ICC in patients with PSC associated with UC.In the first case,a tumor was found by magnetic resonance imaging(MRI)in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain.The second patient was asymptomatic,but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC.ICC was strongly suspected by computed tomography and MRI in both cases,and surgery was performed,but unfortunately,the first patient died of ICC recurrence 16 mo postoperatively,and the second patient died of liver failure 14 mo postoperatively.CONCLUSION Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.
文摘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.
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.
文摘Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown origin mostly found in males, and characterized by diffuse inflammation and fibrosis of both intra- and extra-hepatic bile ducts. So far, PSC is considered as an autoimmune hepatobiliary disease. In most cases the progression of PSC towards liver cirrhosis and liver failure is slow but irreversible, and liver transplantation is currently the only definitive treatment. In recent years,PSC has been an area of active research worldwide with great interest in etiology, pathogenesis, diagnosis, and therapeutic options such as hydrophilic ursodeoxycholic acid and immunosuppressive agent tacrolimus. Recent updates on clinical and therapeutic aspects of PSC are discussed in the present review.
基金Supported by the National Natural Science Foundation of China,No.31960236the Talent Innovation and Entrepreneurship Project of Lanzhou City,No.2019-RC-34the Lanzhou Cheng guan District Science and Technology Planning Project,No.2020SHFZ0029.
文摘Primary sclerosing cholangitis(PSC)is an autoimmune disease characterized by chronic cholestasis,a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis.Gut microbes,consisting of microorganisms colonized in the human gut,play an important role in nutrient intake,metabolic homeostasis,immune regulation,and immune regulation;however,their presence might aid PSC development.Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC.Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria.Dysbiosis of the intestinal flora leads to increased intestinal permeability,homing of intestinal lymphocytes,entry of bacteria and their associated metabolites,such as bile acids,into the liver,stimulation of hepatic immune activation,and promotion of PSC.Currently,PSC effective treatment is lacking.However,a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases(alcoholic liver disease,metabolic fatty liver,cirrhosis,and autoimmune liver disease).In addition,antibiotics,fecal microbiota transplantation,and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis,suggesting their effectiveness for PSC treatment.Therefore,this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.
基金Research Grants from the Inflammatory Bowel Disease Working Group and the American College of Gastroenterology(to Navaneethan U)
文摘Primary sclerosing cholangitis(PSC) is a chronic,cholestatic liver condition characterized by inflammation,fibrosis,and destruction of the intra-and extrahepatic bile ducts.The therapeutic endoscopist plays a key role in the diagnosis and management of PSC.In patients presenting with a cholestatic profile,endoscopic retrograde cholangiopancreatography(ERCP) is warranted for a definite diagnosis of PSC.Dominant strictures of the bile duct occur in 36%-57% of PSC patients.Endoscopic balloon dilatation with or without stenting have been employed in the management of dominant strictures.In addition,PSC patients are at increased risk of developing cholangiocarcinoma with a 20% lifetime risk.Brush cytology obtained during ERCP and use of fluorescence in situ hybridization forms the initial diagnostic step in the investigation of patients with dominant biliary strictures.Our review aims to summarize the current evidence supporting the role of a therapeutic endoscopist in the management of PSC patients.
文摘BACKGROUND A type 2b immunoglobulin G4(IgG4)-related sclerosing cholangitis(SC)without autoimmune pancreatitis is a rare condition with IgG4-SC.While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC,however,the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition.Therefore,the information of our recent case and reported cases have been summarized.CASE SUMMARY We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4,narrowing of the bile duct,its wall thickness,no complication of autoimmune pancreatitis,and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes.The cholangiogram revealed type 2b according to the classification.Corticosteroid treatment showed a favorable effect,with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness.CONCLUSION As isolated type 2b,IgG4-SC is rare,the images,histological findings,and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.
文摘MM: Persistent cholestasis is a rare complication of severe trauma or infections. Little is known about the possible pathomechanisms and the clinical course.METHODS: Secondary sclerosing cholangitis was diagnosed in five patients with persistent jaundice after severe trauma (one burn injury, three accidents, one power current injury). Medical charts were retrospectively reviewed with regard to possible trigger mechanisms for cholestasis, and the clinical course was recorded.RESULTS: Diagnosis of secondary sclerosing cholangitis was based in all patients on the primary sclerosing cholangitis (PSC)-Iike destruction of the intrahepatic bile ducts at cholangiography after exclusion of PSC. In four patients, arterial hypotension with subsequent ischemia may have caused the bile duct damage, whereas in the case of power current injury direct thermal damage was assumed to be the trigger mechanism. The course of secondary liver fibrosis was rapidly progressive and proceeded to liver cirrhosis in all four patients with a follow-up 〉2 years. Therapeutic possibilities were limited.CONCLUSION: Posttraumatic sderosing cholangitis is a rare but rapidly progressive disease, probably caused by ischemia of the intrahepatic bile ducts via the peribiliary capillary plexus due to arterial hypotension.Gastroenterologists should be aware of this disease in patients with persistent cholestasis after severe trauma.
文摘AIM:To clarify the characteristic features of biliary le-sions in patients with autoimmune pancreatitis(AIP) and compare them with those of primary sclerosing cholangitis(PSC) .METHODS:The clinicopathological characteristics of 34 patients with sclerosing cholangitis(SC) associated with AIP were compared with those of 4 patients with PSC.RESULTS:SC with AIP occurred predominantly in el-derly men.Obstructive jaundice was the most frequent initial symptom in SC with AIP.Only SC patients with AIP had elevated serum IgG4 levels,and sclerosing diseases were more frequent in these patients.SC pa-tients with AIP responded well to steroid therapy.Seg-mental stenosis of the lower bile duct was observed only in SC patients with AIP,but a beaded and pruned-tree appearance was detected only in PSC patients.Dense infi ltration of IgG4-positive plasma cells was de-tected in the bile duct wall and the periportal area,as well as in the pancreas,of SC patients with AIP.CONCLUSION:SC with AIP is distinctly different from PSC.The two diseases can be discriminated based on cholangiopancreatographic findings and serum IgG4 levels.
文摘To our knowledge,patients with immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)associated with autoimmune hemolytic anemia(AIHA)have not been reported previously.Many patients with IgG4-SC have autoimmune pancreatitis(AIP)and respond to steroid treatment.However,isolated cases of IgG4-SC are difficult to diagnose.We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis.The patient was a73-year-old man who was being treated for dementia.Liver dysfunction was diagnosed on blood tests at another hospital.Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis,but a rapidly progressing anemia developed simultaneously.After the diagnosis of AIHA,steroid treatment was begun,and the biliary stricture improved.IgG4-SC without AIP was thus diagnosed.
基金Supported by Grants-in-Aid for Clinical Research from National Hospital Organization,Grants-in-Aid for Scientific Research from the Ministry of Health,Labour and Welfare of Japan
文摘Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis,except epidemic schistosomiasis.Among them,primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues,giving rise to systemic amyloidosis,due to a progressive and unresolved inflammatory process,and its possible association with inflammatory bowel diseases.Nevertheless,only one such case has been reported in the literature to date.We report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis,without any evidence of other inflammatory disorders.As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4,the presence of IgG4 + plasma cells was examined systemically,resulting in unexpected documentation of Congo-red-positive amyloid deposits,but not IgG4 + plasma cells,in the liver,stomach and salivary glands.Elevated serum IgG4 is the hallmark of IgG4-related disease,including IgG4-associated cholangitis,but it has also been demonstrated in certain patients with PSC.Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.