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ERCP for primary sclerosing cholangitis (PSC): An acceptable risk?
HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995
9 ERCP (PSC):
AASLD ABSTRACTS
FOR P R I M A R Y S C L E R O S I N G C H O L A N G I T I S AN ACCEPTABLE RISK? SJ van den Hazel, D__J.
van Leeuwen (Dutch Multicenter PSC study group). Div. of GI & Hepatology, Academic Medical Center, University of Amsterdam, NL, and The University of Alabama at Birmingham, USA. Introduction: ERCP is an important diagnostic procedure for the diagnosis of primary sclerosing cholangitis (PSC). However, complications associated with ERCP such as induction or worsening of cholangitis are feared. The aim of our prospective study was to determine the incidence of cholangitis and other complications in patients undergoing diagnostic and/or therapeutic ERCP for PSC. Methods: A multicenter study was performed in patients who underwent ERCP for (suspected) PSC. A 1 week follow-up was made for the occurrence of complications after the procedure. Uniform definitions were applied to establish the most common complications following ERCP. Results: 106 ERCPs were performed in 83 patients. Three did not have PSC. Ten complications occurred (9%): pancreatitis (3), cholangitis (2), increase of cholestasis (2), bleeding postsphincterotomy (1), cystic duct perforation (1), and venous thrombosis (1). All complications resolved quickly with medical therapy. Complications were increased (9/46) if ERCP was performed to evaluate a specific complaint (jaundice, recurrent cholangitis) compared to diagnostic ERCP (1 / 42, p = 0.08). Therapeutic interventions during ERCP (stone removal, placement of stent, stricture dilation) also increased the risk of post-procedural complications (relative risk = 5.04, p = 0.03). Conclusion: Diagnostic ERCP for assumed PSC has a low (4%) complication rate, provides a diagnosis, and gives an indication of treatment options. Therapeutic ERCP for PSC patients is associated with a higher complication rate (16%), but should currently be accepted since only liver transplantation would provide a therapeutic alternative in certain symptomatic patients.
]_] HEPATIC ARTERY RESISTANCE INDEX PREDICTS EARLY DEATH IN CHILDREN WITH BILIARYATRESlA. E. Broide. P. Fenant. F. Reid. A. Biker. H. Meire. M. Rela. N. Heafon. G. Mieit-Veroeni end A. M0wal. Dept. of Child Health, Liver Transplantation Unit, IQng's College Hospital, London. Innovative surgery has been exlremely successful in providing more organs suitable for paediatdc liver transplantation (OLT), pmtlculmly into infants, but there is still a significant shortfall in the number of organs available. Patients re©ognisedto be at dsk of mpld deterioration require early listing for OLT while they are in good clinical condition, and should be given pdorityfor organs. Hepatic artery resistance index (RI) was measured by ultrasoundDoppler in childrenwUh billary a~."sta (BA). 36 were identifind between 1986 and 1994 w#h Ri>I. Clinlcat, • biochemical, uitmsonogmphlcand outcome data ware awdobie In 32 (group A) mean age 0.87 yr; 15 males. These data were compared with those from 32 age matched patients with BA and RI <1.0 (group B). Group A was found to hive stgnificanl worse avar function tests (serum AST, albumin, billrubin, INR). Liver function lasts con'elated with resistance index in group B only. In group A all patients died (n=11) or underwent tmnsplaniation (n=21 of whom 4 died), compared w#h only 2 of group B who died, and 4 were tmnsplsNed without fataflty. No survival occurred without transplantatien In group A beyond 13 months compared with 92% proJeded5 year survival In group B (I)<0.0001). RI (.0<0.0004) end serum bilirubin (p<0.0003) were best predictors of death. When entered Into J, two component model to predict sunAvst, RJ was shown to be the independentvodable and serum billmbln the dependent. We suggestthai regular ultrasound Doppler examination In patients with BA can detect a groupwith RI>I.O who have a high dsk of early modatity. Such patients require ean'y evaluation and listing for OLT. Patients ~th BA already listed for OLT require 2-3 monthly ullmsma~ examinations with immediate upgrading of those found to have RI of 1.0 or above. Recognition and treatment of these pJients may reduce waiting-list morleilly and improve results.
109A
10 ARE BILE DUCT EPITHELIAL CELLS CAPABLE OF ACTING AS P R O F E S S I O N A L A N T I G E N P R E S E N T I N G CELLS IN PRIMARY SCLEROSING CHOLANGITIS ? Eduardo B Martins, Roger W Chapman, Kenneth A Fleming*. Department of Gastroenterology and *Nuffield Department of Pathology, Oxford Radcliffe Hospital. Oxford, UK. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology, where biliary epithelium aberrantly expresses HLA-DR. It is unclear whether bile duct epithelial eeUs can present antigen to CD4 T-cells. To activate T-lymphocytes, antigen preseming cells (APC) have to express co-stimulatory molecules such as CD80 (B7/BB1), otherwise T-cells either become anergic or may undergo apoptosis. AIM: To assess whether HLA-DR positive biliary epithelium in PSC can also express CD80. METHODS: Liver biopsies from 10 PSC (6 stage 1-2), 10 primary biliary cirrhosis (PBC) (8 stage 1-2), 6 auto-immune hepatitis (AIH), 9 obstructive jaundice, 6 alcoholic liver disease and 6 normal livers were analyzed for CD80 and HLA-DR expression by immunohistochemistry, using the APAAP technique. RESULTS: In PSC 25% of interlobular bile ducts expressed both HLA-DR and CD80, compared with 6.8% and 4.5% of interlobular ducts in PBC and AIH respectively (both p<0.05, Fisher's exact test), and in none of the other conditions studied. Proliferating ductules, when present, were negative in all other liver biopsies apart from PSC, where 100% of proliferating ducts co-expressed CDS0 and HLA-DR. CONCLUSION: Bile duct epithdial cells in PSC may act as APC, being capable of activating CD4 T-cells and therefore be may involved in disease etiopathogenesis.
12 F2-ISOPROSTANE EXCRETION IN HUMAN BILE OF PATIENTS WITH BILIARY TRACT AND PANCREATIC DISORDERS. MA Leo, SI Aleynik. JH Siegel, F Kasmin, MK Aleynik, CS Lieber. Section of Liver Disease & Nutr., Alcohol Research Ctr., Bronx VA and Beth Israel (North Division) Medical Centers and Mount Sinai School of Medicine, NY, NY. Fz-Isoprostanes (Fz-IP) result from free radical mediated peroxidation of arachidonic acid. They reflect in vivo lipid peroxidation and have been found in human blood and liver• To determine whether they are excreted in human bile, esterified F2-IP were measured by GC/MS in bile collected during 31 endoscopic retrograde cholangio-pancreatographies (ERCP). In 11 subjects with normal ERCP (controls), bile contained significant amounts of F2-1P (188+27 pg/ml). In 10 individuals with bile duct stones, there was a 3-fold increase of F2-1P (523 + 129 pg/ml; p < 0.05). In 10 patients with pancreatic diseases (9 with chronic pancreatitis and 1 with a pancreatic mass) bile Fz-IP were also enhanced (545+112 pg/ml; p<0.01). These increases were significant even when the values were expressed per bile acids. Contrasting with the rise in Fz-IP, there was no significant change in t~-tocopherol, the major physiological antioxidant. However,/3-carotene was decreased in biliary tract and pancreatic diseases (p < 0.05) compared to controls. Serum liver function tests were normal except for bilirubin which was increased together with a rise in alkaline phosphatase. Total lipids, phospholipids, and cholesterol did not significantly differ in the three groups. One of the hypotheses proposed for the pathogenesis of chronic pancreatitis invokes excess production of free oxygen radicals. The !:resent data provide the first evidence supporting such a mechanism in humans. In addition, it is possible that the striking increase in F2-IP may contribute to lithogenesis in the bile. It is also noteworthy that the rise in F2-IP was observed in the presence of a normal concentration of the antioxidant ~-tocopherol and therefore probably reflects production in the liver and/or surrounding tissues• In s,mmary, substantial amounts of Fz-IP were detected in subjects with normal ERCP and a significant rise was observed in pathological states, including chronic pancreatitis and biliary tract stones, documenting in vivo lipid peroxidation in these conditions. This increase could also play a lithogenir role in the bile.
9 ERCP (PSC):
AASLD ABSTRACTS
FOR P R I M A R Y S C L E R O S I N G C H O L A N G I T I S AN ACCEPTABLE RISK? SJ van den Hazel, D__J.
van Leeuwen (Dutch Multicenter PSC study group). Div. of GI & Hepatology, Academic Medical Center, University of Amsterdam, NL, and The University of Alabama at Birmingham, USA. Introduction: ERCP is an important diagnostic procedure for the diagnosis of primary sclerosing cholangitis (PSC). However, complications associated with ERCP such as induction or worsening of cholangitis are feared. The aim of our prospective study was to determine the incidence of cholangitis and other complications in patients undergoing diagnostic and/or therapeutic ERCP for PSC. Methods: A multicenter study was performed in patients who underwent ERCP for (suspected) PSC. A 1 week follow-up was made for the occurrence of complications after the procedure. Uniform definitions were applied to establish the most common complications following ERCP. Results: 106 ERCPs were performed in 83 patients. Three did not have PSC. Ten complications occurred (9%): pancreatitis (3), cholangitis (2), increase of cholestasis (2), bleeding postsphincterotomy (1), cystic duct perforation (1), and venous thrombosis (1). All complications resolved quickly with medical therapy. Complications were increased (9/46) if ERCP was performed to evaluate a specific complaint (jaundice, recurrent cholangitis) compared to diagnostic ERCP (1 / 42, p = 0.08). Therapeutic interventions during ERCP (stone removal, placement of stent, stricture dilation) also increased the risk of post-procedural complications (relative risk = 5.04, p = 0.03). Conclusion: Diagnostic ERCP for assumed PSC has a low (4%) complication rate, provides a diagnosis, and gives an indication of treatment options. Therapeutic ERCP for PSC patients is associated with a higher complication rate (16%), but should currently be accepted since only liver transplantation would provide a therapeutic alternative in certain symptomatic patients.
]_] HEPATIC ARTERY RESISTANCE INDEX PREDICTS EARLY DEATH IN CHILDREN WITH BILIARYATRESlA. E. Broide. P. Fenant. F. Reid. A. Biker. H. Meire. M. Rela. N. Heafon. G. Mieit-Veroeni end A. M0wal. Dept. of Child Health, Liver Transplantation Unit, IQng's College Hospital, London. Innovative surgery has been exlremely successful in providing more organs suitable for paediatdc liver transplantation (OLT), pmtlculmly into infants, but there is still a significant shortfall in the number of organs available. Patients re©ognisedto be at dsk of mpld deterioration require early listing for OLT while they are in good clinical condition, and should be given pdorityfor organs. Hepatic artery resistance index (RI) was measured by ultrasoundDoppler in childrenwUh billary a~."sta (BA). 36 were identifind between 1986 and 1994 w#h Ri>I. Clinlcat, • biochemical, uitmsonogmphlcand outcome data ware awdobie In 32 (group A) mean age 0.87 yr; 15 males. These data were compared with those from 32 age matched patients with BA and RI <1.0 (group B). Group A was found to hive stgnificanl worse avar function tests (serum AST, albumin, billrubin, INR). Liver function lasts con'elated with resistance index in group B only. In group A all patients died (n=11) or underwent tmnsplaniation (n=21 of whom 4 died), compared w#h only 2 of group B who died, and 4 were tmnsplsNed without fataflty. No survival occurred without transplantatien In group A beyond 13 months compared with 92% proJeded5 year survival In group B (I)<0.0001). RI (.0<0.0004) end serum bilirubin (p<0.0003) were best predictors of death. When entered Into J, two component model to predict sunAvst, RJ was shown to be the independentvodable and serum billmbln the dependent. We suggestthai regular ultrasound Doppler examination In patients with BA can detect a groupwith RI>I.O who have a high dsk of early modatity. Such patients require ean'y evaluation and listing for OLT. Patients ~th BA already listed for OLT require 2-3 monthly ullmsma~ examinations with immediate upgrading of those found to have RI of 1.0 or above. Recognition and treatment of these pJients may reduce waiting-list morleilly and improve results.
109A
10 ARE BILE DUCT EPITHELIAL CELLS CAPABLE OF ACTING AS P R O F E S S I O N A L A N T I G E N P R E S E N T I N G CELLS IN PRIMARY SCLEROSING CHOLANGITIS ? Eduardo B Martins, Roger W Chapman, Kenneth A Fleming*. Department of Gastroenterology and *Nuffield Department of Pathology, Oxford Radcliffe Hospital. Oxford, UK. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology, where biliary epithelium aberrantly expresses HLA-DR. It is unclear whether bile duct epithelial eeUs can present antigen to CD4 T-cells. To activate T-lymphocytes, antigen preseming cells (APC) have to express co-stimulatory molecules such as CD80 (B7/BB1), otherwise T-cells either become anergic or may undergo apoptosis. AIM: To assess whether HLA-DR positive biliary epithelium in PSC can also express CD80. METHODS: Liver biopsies from 10 PSC (6 stage 1-2), 10 primary biliary cirrhosis (PBC) (8 stage 1-2), 6 auto-immune hepatitis (AIH), 9 obstructive jaundice, 6 alcoholic liver disease and 6 normal livers were analyzed for CD80 and HLA-DR expression by immunohistochemistry, using the APAAP technique. RESULTS: In PSC 25% of interlobular bile ducts expressed both HLA-DR and CD80, compared with 6.8% and 4.5% of interlobular ducts in PBC and AIH respectively (both p<0.05, Fisher's exact test), and in none of the other conditions studied. Proliferating ductules, when present, were negative in all other liver biopsies apart from PSC, where 100% of proliferating ducts co-expressed CDS0 and HLA-DR. CONCLUSION: Bile duct epithdial cells in PSC may act as APC, being capable of activating CD4 T-cells and therefore be may involved in disease etiopathogenesis.
12 F2-ISOPROSTANE EXCRETION IN HUMAN BILE OF PATIENTS WITH BILIARY TRACT AND PANCREATIC DISORDERS. MA Leo, SI Aleynik. JH Siegel, F Kasmin, MK Aleynik, CS Lieber. Section of Liver Disease & Nutr., Alcohol Research Ctr., Bronx VA and Beth Israel (North Division) Medical Centers and Mount Sinai School of Medicine, NY, NY. Fz-Isoprostanes (Fz-IP) result from free radical mediated peroxidation of arachidonic acid. They reflect in vivo lipid peroxidation and have been found in human blood and liver• To determine whether they are excreted in human bile, esterified F2-IP were measured by GC/MS in bile collected during 31 endoscopic retrograde cholangio-pancreatographies (ERCP). In 11 subjects with normal ERCP (controls), bile contained significant amounts of F2-1P (188+27 pg/ml). In 10 individuals with bile duct stones, there was a 3-fold increase of F2-1P (523 + 129 pg/ml; p < 0.05). In 10 patients with pancreatic diseases (9 with chronic pancreatitis and 1 with a pancreatic mass) bile Fz-IP were also enhanced (545+112 pg/ml; p<0.01). These increases were significant even when the values were expressed per bile acids. Contrasting with the rise in Fz-IP, there was no significant change in t~-tocopherol, the major physiological antioxidant. However,/3-carotene was decreased in biliary tract and pancreatic diseases (p < 0.05) compared to controls. Serum liver function tests were normal except for bilirubin which was increased together with a rise in alkaline phosphatase. Total lipids, phospholipids, and cholesterol did not significantly differ in the three groups. One of the hypotheses proposed for the pathogenesis of chronic pancreatitis invokes excess production of free oxygen radicals. The !:resent data provide the first evidence supporting such a mechanism in humans. In addition, it is possible that the striking increase in F2-IP may contribute to lithogenesis in the bile. It is also noteworthy that the rise in F2-IP was observed in the presence of a normal concentration of the antioxidant ~-tocopherol and therefore probably reflects production in the liver and/or surrounding tissues• In s,mmary, substantial amounts of Fz-IP were detected in subjects with normal ERCP and a significant rise was observed in pathological states, including chronic pancreatitis and biliary tract stones, documenting in vivo lipid peroxidation in these conditions. This increase could also play a lithogenir role in the bile.