Based on histological and immunohistochemical exami- nation of various organs of patients with autoimmune pancreatitis （AIP）, a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. ...Based on histological and immunohistochemical exami- nation of various organs of patients with autoimmune pancreatitis （AIP）, a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. This is a systemic disease that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prosrate, in which tissue fibrosis with obliterative phlebitis is pathologically induced. AlP is not simply pancreatitis but, in fact, is a pancreatic disease indicative of IgG4- related sclerosing diseases. This disease includes AlP, sclerosing cholangitis, cholecystitis, sialadenitis, retro-peritoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia, prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most IgG4-related sclerosing diseases have been found to be associated with AlP, but also those without pancreatic involvement have been reported. In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected. The disease occurs predominantly in older men and responds well to steroid therapy. Serum IgG4 levels and immunos-taining with anti-IgG4 antibody are useful in making the diagnosis. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery.展开更多
The three major immune disorders of the liver are autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC) and primary sclerosing cholangitis(PSC).Variant forms of these diseases are generally called overlap syndromes...The three major immune disorders of the liver are autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC) and primary sclerosing cholangitis(PSC).Variant forms of these diseases are generally called overlap syndromes,although there has been no standardised definition.Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC.The AIH-PBC overlap syndrome is the most common form,affecting almost 10% of adults with AIH or PBC.Single cases of AIH and autoimmune cholangitis(AMA-negative PBC) overlap syndrome have also been reported.The AIH-PSC overlap syndrome is predominantly found in children,adolescents and young adults with AIH or PSC.Interestingly,transitions from one autoimmune to another have also been reported in a minority of patients,especially transitions from PBC to AIH-PBC overlap syndrome.Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment.Therapy for overlap syndromes is empiric,since controlled trials are not available in these rare disorders.Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes.In end-stage disease,liver transplantation is the treatment of choice.展开更多
Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseas-es(AiLD),namely autoimmune hepatitis types 1 and 2(AIH-1 and 2),primary biliary cirrhosis(PBC),and the s...Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseas-es(AiLD),namely autoimmune hepatitis types 1 and 2(AIH-1 and 2),primary biliary cirrhosis(PBC),and the sclerosing cholangitis variants in adults and children.AIH-1 is specified by anti-nuclear antibody(ANA) and smooth muscle antibody(SMA).AIH-2 is specified by antibody to liver kidney microsomal antigen type-1(anti-LKM1) and anti-liver cytosol type 1(anti-LC1).SMA,ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation.PBC is specified by antimitochondrial antibodies(AMA) react-ing with enzymes of the 2-oxo-acid dehydrogenase complexes(chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly react-ing with nuclear pore gp210 and nuclear body sp100.Sclerosing cholangitis presents as at least two variants,first the classical primary sclerosing cholangitis(PSC) mostly affecting adult men wherein the only(and non-specific) reactivity is an atypical perinuclear antineutro-phil cytoplasmic antibody(p-ANCA),also termed peri-nuclear anti-neutrophil nuclear antibodies(p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis(ASC) with serological features resembling those of type 1 AIH.Liver diagnostic serol-ogy is a fast-expanding area of investigation as new purified and recombinant autoantigens,and automatedtechnologies such as ELISAs and bead assays,become available to complement(or even compete with) tradi-tional immunofluorescence procedures.We survey for the first time global trends in quality assurance impact-ing as it does on(1) manufacturers/purveyors of kits and reagents,(2) diagnostic service laboratories that fulfill clinicians' requirements,and(3) the end-user,the physician providing patient care,who must properly interpret test results in the overall clinical context.展开更多
AIM To investigate the efficacy and safety of emergency endoscopic retrograde cholangiopancreatography(ERCP) in elderly patients with acute cholangitis. METHODS From June 2008 to May 2016, emergency ERCPs were perform...AIM To investigate the efficacy and safety of emergency endoscopic retrograde cholangiopancreatography(ERCP) in elderly patients with acute cholangitis. METHODS From June 2008 to May 2016, emergency ERCPs were performed in 207 cases of acute cholangitis at our institution. Patients were classified as elderly if they were aged 80 years and older(n = 102); controls were under the age of 80 years(n = 105). The patients' medical records were retrospectively reviewed for comorbidities, laboratory data, etiology of cholangitis(presence of biliary stones, biliary stricture and malignancy), details of the ERCP(therapeutic approaches, technical success rates, procedure duration), ERCP-related complications and mortality. RESULTS The frequency of comorbidities was higher in the elderly group than the control group(91.2% vs 67.6%). Periampullary diverticulum was observed in the elderly group at a higher frequency than the control group(24.5% vs 13.3%). Between the groups, there was no significant difference in the technical success rates(95.1% vs 95.2%) or endoscopicprocedure durations. With regard to the frequency of ERCP-related complications, there was no significant difference between the two groups(6.9% vs 6.7%), except for a lower rate of post-ERCP pancreatitis in the elderly group than in the control group(1.0% vs 3.8%). Neither angiographic nor surgical intervention was required in any of the cases with ERCP-related complications. There was no mortality during the observational periods. CONCLUSION Emergency ERCP for acute cholangitis can be performed safely even in elderly patients aged 80 years and older.展开更多
AIM: To determine the NF-kB activity in peripheral blood mononuclear cells (PBMC) in patients with acute cholangitis of severe type (ACST) and correlate the degree of NF-kB activation with severity of biliary tract in...AIM: To determine the NF-kB activity in peripheral blood mononuclear cells (PBMC) in patients with acute cholangitis of severe type (ACST) and correlate the degree of NF-kB activation with severity of biliary tract infection and clinical outcome. METHODS: Twenty patients with ACST were divided into survivor group (13 cases) and nonsurvivor group (7 cases). Other ten patients undergoing elective gastrectomy or inguinal hernia repair were selected as control group. Peripheral blood samples were taken 24 hours postoperatively. PBMC were separated by density gradient centrifugation, then nuclear proteins were isolated from PBMC, and Electrophoretic Mobility Shift Assay (EMSA) used determined. The results were quantified by scanning densitometer of a Bio-Image Analysis System and expressed as relative optical density (ROD). The levels of TNF-alpha, IL-6, and IL-10 in the plasma of patients with ACST and healthy control subjects were determined by using an enzyme-linked immunoassay (ELISA). RESULTS: The NF-kB activity was 5.02 +/- 1.03 in nonsurvivor group, 2.98 +/- 0.51 in survivor group and 1.06 +/- 0.34 in control group. There were statistical differences in three groups (P【0.05). The levels of TNF-alpha and IL-6 in plasma were (498 +/- 53)ng.L(-1)and (587 +/- 64)ng.L(-1)in nonsurvivor group, (284 +/- 32)ng.L(-1) and (318 +/- 49)ng.L(-1)in survivor group and (89 +/- 11)ng.L(-1) and (102 +/-13)ng.L(-1)in control group. All patients with ACST had increased levels of TNF-alpha and IL-6, which were many-fold greater than those of control group, and there was an evidence of significantly higher levels in those of nonsurvivor group than that in survivor group (P【0.05). The levels of IL-10 in plasma were (378+/-32)ng.L(-1), (384+/-37)ng.L(-1) and (68+/-11)ng.L(-1) in three groups, respectively. All patients had also increased levels of IL-10 when compared with control group (P【0.05), but the IL-10 levels were not significantly higher in nonsurvivors than in survivors (P】0.05). CONCLUSION: NF-kB activity in PBMC展开更多
To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). METHODSStool samples were collected and relevant clinical data obtained from 106 study pa...To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). METHODSStool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with (n = 32) or without (n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels. Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data. RESULTSMicrobial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease (IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales. CONCLUSIONPSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes (PSC-IBD and UC).展开更多
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 cho...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.展开更多
文摘Based on histological and immunohistochemical exami- nation of various organs of patients with autoimmune pancreatitis （AIP）, a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. This is a systemic disease that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prosrate, in which tissue fibrosis with obliterative phlebitis is pathologically induced. AlP is not simply pancreatitis but, in fact, is a pancreatic disease indicative of IgG4- related sclerosing diseases. This disease includes AlP, sclerosing cholangitis, cholecystitis, sialadenitis, retro-peritoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia, prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most IgG4-related sclerosing diseases have been found to be associated with AlP, but also those without pancreatic involvement have been reported. In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected. The disease occurs predominantly in older men and responds well to steroid therapy. Serum IgG4 levels and immunos-taining with anti-IgG4 antibody are useful in making the diagnosis. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery.
文摘The three major immune disorders of the liver are autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC) and primary sclerosing cholangitis(PSC).Variant forms of these diseases are generally called overlap syndromes,although there has been no standardised definition.Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC.The AIH-PBC overlap syndrome is the most common form,affecting almost 10% of adults with AIH or PBC.Single cases of AIH and autoimmune cholangitis(AMA-negative PBC) overlap syndrome have also been reported.The AIH-PSC overlap syndrome is predominantly found in children,adolescents and young adults with AIH or PSC.Interestingly,transitions from one autoimmune to another have also been reported in a minority of patients,especially transitions from PBC to AIH-PBC overlap syndrome.Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment.Therapy for overlap syndromes is empiric,since controlled trials are not available in these rare disorders.Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes.In end-stage disease,liver transplantation is the treatment of choice.
文摘Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseas-es(AiLD),namely autoimmune hepatitis types 1 and 2(AIH-1 and 2),primary biliary cirrhosis(PBC),and the sclerosing cholangitis variants in adults and children.AIH-1 is specified by anti-nuclear antibody(ANA) and smooth muscle antibody(SMA).AIH-2 is specified by antibody to liver kidney microsomal antigen type-1(anti-LKM1) and anti-liver cytosol type 1(anti-LC1).SMA,ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation.PBC is specified by antimitochondrial antibodies(AMA) react-ing with enzymes of the 2-oxo-acid dehydrogenase complexes(chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly react-ing with nuclear pore gp210 and nuclear body sp100.Sclerosing cholangitis presents as at least two variants,first the classical primary sclerosing cholangitis(PSC) mostly affecting adult men wherein the only(and non-specific) reactivity is an atypical perinuclear antineutro-phil cytoplasmic antibody(p-ANCA),also termed peri-nuclear anti-neutrophil nuclear antibodies(p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis(ASC) with serological features resembling those of type 1 AIH.Liver diagnostic serol-ogy is a fast-expanding area of investigation as new purified and recombinant autoantigens,and automatedtechnologies such as ELISAs and bead assays,become available to complement(or even compete with) tradi-tional immunofluorescence procedures.We survey for the first time global trends in quality assurance impact-ing as it does on(1) manufacturers/purveyors of kits and reagents,(2) diagnostic service laboratories that fulfill clinicians' requirements,and(3) the end-user,the physician providing patient care,who must properly interpret test results in the overall clinical context.
文摘AIM To investigate the efficacy and safety of emergency endoscopic retrograde cholangiopancreatography(ERCP) in elderly patients with acute cholangitis. METHODS From June 2008 to May 2016, emergency ERCPs were performed in 207 cases of acute cholangitis at our institution. Patients were classified as elderly if they were aged 80 years and older(n = 102); controls were under the age of 80 years(n = 105). The patients' medical records were retrospectively reviewed for comorbidities, laboratory data, etiology of cholangitis(presence of biliary stones, biliary stricture and malignancy), details of the ERCP(therapeutic approaches, technical success rates, procedure duration), ERCP-related complications and mortality. RESULTS The frequency of comorbidities was higher in the elderly group than the control group(91.2% vs 67.6%). Periampullary diverticulum was observed in the elderly group at a higher frequency than the control group(24.5% vs 13.3%). Between the groups, there was no significant difference in the technical success rates(95.1% vs 95.2%) or endoscopicprocedure durations. With regard to the frequency of ERCP-related complications, there was no significant difference between the two groups(6.9% vs 6.7%), except for a lower rate of post-ERCP pancreatitis in the elderly group than in the control group(1.0% vs 3.8%). Neither angiographic nor surgical intervention was required in any of the cases with ERCP-related complications. There was no mortality during the observational periods. CONCLUSION Emergency ERCP for acute cholangitis can be performed safely even in elderly patients aged 80 years and older.
基金the National Natural Science Foundation of China,No.39970719,30170919
文摘AIM: To determine the NF-kB activity in peripheral blood mononuclear cells (PBMC) in patients with acute cholangitis of severe type (ACST) and correlate the degree of NF-kB activation with severity of biliary tract infection and clinical outcome. METHODS: Twenty patients with ACST were divided into survivor group (13 cases) and nonsurvivor group (7 cases). Other ten patients undergoing elective gastrectomy or inguinal hernia repair were selected as control group. Peripheral blood samples were taken 24 hours postoperatively. PBMC were separated by density gradient centrifugation, then nuclear proteins were isolated from PBMC, and Electrophoretic Mobility Shift Assay (EMSA) used determined. The results were quantified by scanning densitometer of a Bio-Image Analysis System and expressed as relative optical density (ROD). The levels of TNF-alpha, IL-6, and IL-10 in the plasma of patients with ACST and healthy control subjects were determined by using an enzyme-linked immunoassay (ELISA). RESULTS: The NF-kB activity was 5.02 +/- 1.03 in nonsurvivor group, 2.98 +/- 0.51 in survivor group and 1.06 +/- 0.34 in control group. There were statistical differences in three groups (P【0.05). The levels of TNF-alpha and IL-6 in plasma were (498 +/- 53)ng.L(-1)and (587 +/- 64)ng.L(-1)in nonsurvivor group, (284 +/- 32)ng.L(-1) and (318 +/- 49)ng.L(-1)in survivor group and (89 +/- 11)ng.L(-1) and (102 +/-13)ng.L(-1)in control group. All patients with ACST had increased levels of TNF-alpha and IL-6, which were many-fold greater than those of control group, and there was an evidence of significantly higher levels in those of nonsurvivor group than that in survivor group (P【0.05). The levels of IL-10 in plasma were (378+/-32)ng.L(-1), (384+/-37)ng.L(-1) and (68+/-11)ng.L(-1) in three groups, respectively. All patients had also increased levels of IL-10 when compared with control group (P【0.05), but the IL-10 levels were not significantly higher in nonsurvivors than in survivors (P】0.05). CONCLUSION: NF-kB activity in PBMC
基金Supported by Ministry of Health of the Czech Republic,No.15-28064A
文摘To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). METHODSStool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with (n = 32) or without (n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels. Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data. RESULTSMicrobial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease (IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales. CONCLUSIONPSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes (PSC-IBD and UC).
文摘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.
