- Email: [email protected]
Autoimmune hepatitis in children: Predictors for orthotopic liver transplant evaluation
Initially, mean total bilirnbin, serum albumin, and ALT were 66 mg/dL, 2.9 mg/dl and 450 IU/L in gp A vs. 4 mg/dL, 3.8 mg/dL and 878 IU/L m gp B respectively (p = NS). The mean prothmmbin time (PT) of 17 seconds in gp A patients was prolonged cmnpared to 13.3 sec in gp B (p =0.05). All patients in gp A were diagnosed with type I AIH; in gp B 6 had type 1 AIH, 1 patient had type 2 AIH, while 3 were only ANA positive (p=NS) Liver histology at presentation revealed at least stage 2 cirrhosis in all (100%) in gp A cmnpared to 5 (50%) in gp B. Mean steroid dose used for induction of remission was 0 9 m gp A in contrast to 1.3 mg/kg/d in gp B. In the tbrmer gp none of the patients attained remission, 2 are post OLT, whereas 2 of the 3 0 L T listed patients are now on FK506 In gp B, all patients are on azathioprine/6-mercaptopurine in a state of remission, all but 2 are off steroids. There was no correlation between albumin, PT, and the type of AIH with cirrhotic and non-cirrhotic patients in this series. Conclusion: In children with AIH, prolonged Vr may predict poor response to medical management and may indicate the need tbe an early evaluation for OLT. We did not flnd a correlation of initial hepatic syntbetic fnnctinns with cirrhosis, but they may be a predictor of poor response in a larger cohort of patients ~Batts et al. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995;19:1409-17
significantly < 0 m the 4 age groups at diagnosis (G1 -0.66, G2 -1.05, G3 -1.18, G4 -117) and oornlaliaed after one year in the 2 younger groups and at 2 years in the older goups. Height gains (delta z-scores) were present at one year ( group A: 0.81 vs group B: 030 ) and at 3 years (group A: 141 vs. group B: 0.51 ) Height gain was > 0 at 2 and 3 years even in children who wmv above average at the time of diagnosis (group B) In the population studied, 83% of patients with CD had a normal height for age (z > -2.0) at diagnosis. CONCLUSION: Even children who were of average height at diagnosis had catchup growth and maintained it after three ),ears of a GFD, indicating prior suboptimal growth .Weight recovery was parallel to that of height. The overweight observed in group 2 during the third year roight be explained by the family attitude towards these children, aiming at a laster nutritional recovery"
T1354 The EfflcaW of Ondansetron in Attenuating Symptoms of Cyclic Vomiting Bhanu K. Sunku, B. U. la Terming Maa, John R. Hayes
Clinical ~ n
Background: Cyclic vomiting syndrome (CVS) is characterized by a clinical pattern of recurrent episodes of severe vomiting between which the child is normal. Because the pathophysinlo D, is unknovm, empiric therapy has been directed towards either preventing eDsodes , or aborting them in patients with infrequent episodes or attacks refractor}" to prophylaxis. In this study, we prospectively examined the efficacy of oral and IV ondansetmn used during acute episodes of CVS. Methods: A total of 25 patients meeting the consensus criteria for CVS were studied prospectively using a questionnaire: 17 patients were prescribed oral ondansetron and 14 patients received IV ondansetron dosed at 0.3 mg/kg, both administered at the onset of the episode Six patients were evaluated for both the IV and PO forms in separate episodes. Parents filled out a questinnnaim to e'
and follow.up.
n (f=md.) Age (yr), median (range) Symptomduration (wk), mean Follow-up (yr), median (range) Jaundice (%) Abdominal pain (%) FalJgue(%) oe.~(~)
~pA 5 (5) 12 (8-15) 5 2 (1.5-7) 90 40 0 4o
GpB lo (9) 10 (2-16) 13.5
2.5 (0.5-13) 70 70 30 30
T1357 CDP571, a Humanized Monoclonal Antibody to TNFmt, a Well Tolerated Alternative in Crohn's Disease Patients who have Experienced Hypersensitivity Reactions to Infliximab Stephen Hanauer, Daniel Present, Stephan R, Targan, kori Ram, Jatin Patel, wilham J. Sandbom Background: CDP571 is a novel humanized monoclonal antibody to tumor necrosis factor (TNF)-cc The aim of the study was to assess the tolerabifity of a single infusion of CDP571 in Crohn's disease patients with a histor}, of hypersensitivity' to infliximab. Hypersensitivity to inlliximab has been reported to correlate with the presence of human anti-chimeric antibodies (HACA), which may also decrease the plasma concentrations of the drag. Methods: 22 adult patients with Crohn's disease who had experienced either acute hypersensitivity reactions (AHR) ( n = l l ) or delayed hypersensitivity reactions (DHR) (n= 11) to infliximab were enrolled m this multicenter, open-label study Blood samples were taken at screening to confirm non-cross reactivity of plasma with CDP571 and for baseline analysis of HACA. Patients received a single intravenous dose of CDP57I (10 mg/kg) over 2 hours and were subsequently assessed for 4 weeks by standard clinical and laboratory analyses. Plasma samples were analyzed for CDP571 plasma concentrations and antibodies to CDP571 Crohn's disease was monitored using the CDAL Results: All patients had previously received ->2 doses of infliximab and 17/22 were found to have HACA. No cross-reactivity to CDP571 was found 21/22 patients completed the study One patient was withdrawn 13 days after the infusion due to disease progression. One patient experienced an acute reaction 1.7 hours into the infusion of CDP571, devdoping cough/dyspnea, which was treated *,vithdiphenylhydramme. One patient experienced a possible DHR 16-20 days post-infusion, developing urticaria, headache and artbralgias similar to previous reaction experienced with inflLximab, but less severe. No antibodies to CDP571 were detected in an}, of the 22 patients and the plasma concentrations of CDP571 were consistent with those observed in previous studies. During the study, 11 patients experienced 44 adverse events (AEs) - - mostly mild or moderate. 3 serious AEs were reported, none of which were considered related to the stud?/"medication. Clinical response (decrease in CDAi ->70 points) was observed in 9/22 (41%) patients by"Week 4, with no differences between the AHR and DHR groups. 5 of the 22 patients (23%) showed a decrease in CDAI >100 points. Conclusion: CDP571 is well tolerated and may provide an ahernative option in patients who have previously experienced hypersensitivity to inlhximab.
T1355
Comparison of Fecal L/pose Test and Fecal Elastase-1 Test in the Assessment of Exocrine Pancreatic Function in Cystic Fibrosis jaroslasv Walkowiak, Karl-Heinz Heraig, Kryst?/maStrzykala, Julinsz Prayslawski, Marian Graymis/awski, Marian Krawczy'nski Ot~ective: In pediatric patients, indirect tests am preferred because of their less invasive character. Among those, fecal elastase-1 test has so far been shown been shown to have the highest senmtivity and specificity. However, the role of the ti:cal lipase test in the diagnostic work up for pancreatic insufficiency in cystic hbmsis patients has not been defined. Therefbre, the aim of the present study was to compare the sensitivity and the specificity of fecal lipase (lP) test to the fecal e]astase-1 (El) test in the assessment of exocrine pancreatic function. Material gr methods: 63 CF patients and 95 HS on normal fat intake were evaluated. In all sultjects, E1 concentration (H.1SA) and LP activity (ELISA) ',',,ere measured. In 50 HS, ~mple-to-sample (n = 3) variation from the same stool and day-to-day variation from three consecutive stools were determined twice. The presence of pancreatic insufficiency patients was documented in 55 pancreatic it~nfficient CF patients by tire determination of fecal fat excretion and in 12 pancreatic sufficient patients by' the (hrect test The sensitivity" and specificity ot the E1 test and LP test were compared. Results: The sample-to-sample variation (mean + SEM 13 2 + 1.2 % vs. 23.4 + 2.2%) and day-to-day variation (mean + SEM: ]6.3 + 1.2% vs 325 + 26%) were significantly lower (p<0.0001) for E1 determinations tMn for LP measuremenl:s With the cut-off levds giving tire same specificity ['or both tests (95 8%), the sensitivity ot fecal elasrase-1 test (87.3%) was significantly higher (p<0.04) than Ihat of fecal lipase test (778%). In conclusion, tecal lipase test is less sensitive than fecal elastase-i test w'ith a comparable specificity in the assessment of CF pancreatic involvement.
T1358 A Prospective Cohort Study of the Influence of Nonsteroidal Anti-inflammatory Drugs on Disease Activity in Outpatients with Inflammatory Bowel Disease (IBD) Gregory F. Bonner, Alifiya Fakhri, Sridhar R. Vennamaneni
T1356
Aims: We examined whether use of nonsteroidal anti-inflammatory drags (NSAIDs) in oupatients with IBD was associated with increased severity of disease activity. Methods: 426 outpatients with Crohn's disease (CD) and 203 with ulcerative colitis (UC) were followed from November 1997 to April 2002. Patients were questioned at each ,,/sit regarding any use of prescription or OTC NSAIDs and a clinical disease activity index (modified Harvey Bradshaw (MHB) or Lichtiger score (LS)) was obtained A moderately active flare was defined as an MHB score of 7 or LS of 8. Patients with an ostomy or J-pouch surgery were excluded. NSAID use was dwided into low-dose (ASA 325 mg/d or less or equivalent doses of other NSAIDs) or high-dose, hrdividual patients could have multiple visits and each visit was counted separately. Statistical analysis was performed using the GEE regression model. Results: CD patients had 1315 visits with no NSAIDs, 215 visits with tow-dose NSAIDs and 139 visits with high-dose NSAIDs. UC patients had 495 visits w'ith no NSA1Ds, 112 lowdose NSAIDs, and 49 high-dose NSAIDs. For CD, the average MHB score was 4.07 for the no-NSAID group, 4.24 for tow-dose NSAIDs (p=0.46) and 4.78 for high-dose NSAIDs
Autuimmune Hepatitis in Children: Predictors for Orthotopic Liver Transplant Evaluation Mahmoud Sabri, John Peters, Maria Clavell, Seema Khan Background: Autoimmune hepatitis (AIH) is a chronic liver disease that may, progress to cirrhosis and death if left untreated. Data at initial presentation on predictors of outcome in children with AIH are scarce. Aim: To assess dinicohistologic parameters as predictors oi medical treatment outcome in children with AIH. Methods: We re,hewed retrospectively climcal data related to 15 children (14 temales), median age 11 y (range, 2-16) with A1H followed at our center since 1989. Clinical presentation, laboratory tests, and liver histology were compared between two groups: gp A with patients either listed or post orthotopic liver transplant (OLT) (n = 5), and gp B with patients in clinical remission with medical management (n= 10). We defined clinical remission as hepatic transaminases less than 2-fold normal; liver histology, was staged according to prev/onaly published criteria ~. Results:
A-517
AGA Abstracts
significantly < 0 m the 4 age groups at diagnosis (G1 -0.66, G2 -1.05, G3 -1.18, G4 -117) and oornlaliaed after one year in the 2 younger groups and at 2 years in the older goups. Height gains (delta z-scores) were present at one year ( group A: 0.81 vs group B: 030 ) and at 3 years (group A: 141 vs. group B: 0.51 ) Height gain was > 0 at 2 and 3 years even in children who wmv above average at the time of diagnosis (group B) In the population studied, 83% of patients with CD had a normal height for age (z > -2.0) at diagnosis. CONCLUSION: Even children who were of average height at diagnosis had catchup growth and maintained it after three ),ears of a GFD, indicating prior suboptimal growth .Weight recovery was parallel to that of height. The overweight observed in group 2 during the third year roight be explained by the family attitude towards these children, aiming at a laster nutritional recovery"
T1354 The EfflcaW of Ondansetron in Attenuating Symptoms of Cyclic Vomiting Bhanu K. Sunku, B. U. la Terming Maa, John R. Hayes
Clinical ~ n
Background: Cyclic vomiting syndrome (CVS) is characterized by a clinical pattern of recurrent episodes of severe vomiting between which the child is normal. Because the pathophysinlo D, is unknovm, empiric therapy has been directed towards either preventing eDsodes , or aborting them in patients with infrequent episodes or attacks refractor}" to prophylaxis. In this study, we prospectively examined the efficacy of oral and IV ondansetmn used during acute episodes of CVS. Methods: A total of 25 patients meeting the consensus criteria for CVS were studied prospectively using a questionnaire: 17 patients were prescribed oral ondansetron and 14 patients received IV ondansetron dosed at 0.3 mg/kg, both administered at the onset of the episode Six patients were evaluated for both the IV and PO forms in separate episodes. Parents filled out a questinnnaim to e'
and follow.up.
n (f=md.) Age (yr), median (range) Symptomduration (wk), mean Follow-up (yr), median (range) Jaundice (%) Abdominal pain (%) FalJgue(%) oe.~(~)
~pA 5 (5) 12 (8-15) 5 2 (1.5-7) 90 40 0 4o
GpB lo (9) 10 (2-16) 13.5
2.5 (0.5-13) 70 70 30 30
T1357 CDP571, a Humanized Monoclonal Antibody to TNFmt, a Well Tolerated Alternative in Crohn's Disease Patients who have Experienced Hypersensitivity Reactions to Infliximab Stephen Hanauer, Daniel Present, Stephan R, Targan, kori Ram, Jatin Patel, wilham J. Sandbom Background: CDP571 is a novel humanized monoclonal antibody to tumor necrosis factor (TNF)-cc The aim of the study was to assess the tolerabifity of a single infusion of CDP571 in Crohn's disease patients with a histor}, of hypersensitivity' to infliximab. Hypersensitivity to inlliximab has been reported to correlate with the presence of human anti-chimeric antibodies (HACA), which may also decrease the plasma concentrations of the drag. Methods: 22 adult patients with Crohn's disease who had experienced either acute hypersensitivity reactions (AHR) ( n = l l ) or delayed hypersensitivity reactions (DHR) (n= 11) to infliximab were enrolled m this multicenter, open-label study Blood samples were taken at screening to confirm non-cross reactivity of plasma with CDP571 and for baseline analysis of HACA. Patients received a single intravenous dose of CDP57I (10 mg/kg) over 2 hours and were subsequently assessed for 4 weeks by standard clinical and laboratory analyses. Plasma samples were analyzed for CDP571 plasma concentrations and antibodies to CDP571 Crohn's disease was monitored using the CDAL Results: All patients had previously received ->2 doses of infliximab and 17/22 were found to have HACA. No cross-reactivity to CDP571 was found 21/22 patients completed the study One patient was withdrawn 13 days after the infusion due to disease progression. One patient experienced an acute reaction 1.7 hours into the infusion of CDP571, devdoping cough/dyspnea, which was treated *,vithdiphenylhydramme. One patient experienced a possible DHR 16-20 days post-infusion, developing urticaria, headache and artbralgias similar to previous reaction experienced with inflLximab, but less severe. No antibodies to CDP571 were detected in an}, of the 22 patients and the plasma concentrations of CDP571 were consistent with those observed in previous studies. During the study, 11 patients experienced 44 adverse events (AEs) - - mostly mild or moderate. 3 serious AEs were reported, none of which were considered related to the stud?/"medication. Clinical response (decrease in CDAi ->70 points) was observed in 9/22 (41%) patients by"Week 4, with no differences between the AHR and DHR groups. 5 of the 22 patients (23%) showed a decrease in CDAI >100 points. Conclusion: CDP571 is well tolerated and may provide an ahernative option in patients who have previously experienced hypersensitivity to inlhximab.
T1355
Comparison of Fecal L/pose Test and Fecal Elastase-1 Test in the Assessment of Exocrine Pancreatic Function in Cystic Fibrosis jaroslasv Walkowiak, Karl-Heinz Heraig, Kryst?/maStrzykala, Julinsz Prayslawski, Marian Graymis/awski, Marian Krawczy'nski Ot~ective: In pediatric patients, indirect tests am preferred because of their less invasive character. Among those, fecal elastase-1 test has so far been shown been shown to have the highest senmtivity and specificity. However, the role of the ti:cal lipase test in the diagnostic work up for pancreatic insufficiency in cystic hbmsis patients has not been defined. Therefbre, the aim of the present study was to compare the sensitivity and the specificity of fecal lipase (lP) test to the fecal e]astase-1 (El) test in the assessment of exocrine pancreatic function. Material gr methods: 63 CF patients and 95 HS on normal fat intake were evaluated. In all sultjects, E1 concentration (H.1SA) and LP activity (ELISA) ',',,ere measured. In 50 HS, ~mple-to-sample (n = 3) variation from the same stool and day-to-day variation from three consecutive stools were determined twice. The presence of pancreatic insufficiency patients was documented in 55 pancreatic it~nfficient CF patients by tire determination of fecal fat excretion and in 12 pancreatic sufficient patients by' the (hrect test The sensitivity" and specificity ot the E1 test and LP test were compared. Results: The sample-to-sample variation (mean + SEM 13 2 + 1.2 % vs. 23.4 + 2.2%) and day-to-day variation (mean + SEM: ]6.3 + 1.2% vs 325 + 26%) were significantly lower (p<0.0001) for E1 determinations tMn for LP measuremenl:s With the cut-off levds giving tire same specificity ['or both tests (95 8%), the sensitivity ot fecal elasrase-1 test (87.3%) was significantly higher (p<0.04) than Ihat of fecal lipase test (778%). In conclusion, tecal lipase test is less sensitive than fecal elastase-i test w'ith a comparable specificity in the assessment of CF pancreatic involvement.
T1358 A Prospective Cohort Study of the Influence of Nonsteroidal Anti-inflammatory Drugs on Disease Activity in Outpatients with Inflammatory Bowel Disease (IBD) Gregory F. Bonner, Alifiya Fakhri, Sridhar R. Vennamaneni
T1356
Aims: We examined whether use of nonsteroidal anti-inflammatory drags (NSAIDs) in oupatients with IBD was associated with increased severity of disease activity. Methods: 426 outpatients with Crohn's disease (CD) and 203 with ulcerative colitis (UC) were followed from November 1997 to April 2002. Patients were questioned at each ,,/sit regarding any use of prescription or OTC NSAIDs and a clinical disease activity index (modified Harvey Bradshaw (MHB) or Lichtiger score (LS)) was obtained A moderately active flare was defined as an MHB score of 7 or LS of 8. Patients with an ostomy or J-pouch surgery were excluded. NSAID use was dwided into low-dose (ASA 325 mg/d or less or equivalent doses of other NSAIDs) or high-dose, hrdividual patients could have multiple visits and each visit was counted separately. Statistical analysis was performed using the GEE regression model. Results: CD patients had 1315 visits with no NSAIDs, 215 visits with tow-dose NSAIDs and 139 visits with high-dose NSAIDs. UC patients had 495 visits w'ith no NSA1Ds, 112 lowdose NSAIDs, and 49 high-dose NSAIDs. For CD, the average MHB score was 4.07 for the no-NSAID group, 4.24 for tow-dose NSAIDs (p=0.46) and 4.78 for high-dose NSAIDs
Autuimmune Hepatitis in Children: Predictors for Orthotopic Liver Transplant Evaluation Mahmoud Sabri, John Peters, Maria Clavell, Seema Khan Background: Autoimmune hepatitis (AIH) is a chronic liver disease that may, progress to cirrhosis and death if left untreated. Data at initial presentation on predictors of outcome in children with AIH are scarce. Aim: To assess dinicohistologic parameters as predictors oi medical treatment outcome in children with AIH. Methods: We re,hewed retrospectively climcal data related to 15 children (14 temales), median age 11 y (range, 2-16) with A1H followed at our center since 1989. Clinical presentation, laboratory tests, and liver histology were compared between two groups: gp A with patients either listed or post orthotopic liver transplant (OLT) (n = 5), and gp B with patients in clinical remission with medical management (n= 10). We defined clinical remission as hepatic transaminases less than 2-fold normal; liver histology, was staged according to prev/onaly published criteria ~. Results:
A-517
AGA Abstracts