Use of International Autoimmune Hepatitis Group Criteria for Pediatric Patients

1. Use of International Autoimmune Hepatitis Group Criteria for Pediatric Patients in a North American Primary Sclerosing Cholangitis/AIH Registry (STOPSC) Dennis Black1,3, Ravinder Anand2, Wanrong Yin2, Gene Whitington3 and the STOPSC Research Group Dept. of Pediatrics, University of Tennessee Health Science Center, Memphis, TN; The EMMES Corporation, Rockville, MD; Le Bonheur Children’s Medical Center, Memphis, TN DISCLOSURES PURPOSE RESULTS The following people have nothing to disclose: Dennis D. Black Ravinder Anand Wanrong Yin Gene L. Whitington • To determine the utility of the AIH diagnostic criteria established by the International AIH Group (IAIHG) (Alvarez et al, Journal of Hepatology, 31:929-938, 1999) in pediatric patients with an existing diagnosis of AIH recruited into a PSC/AIH registry • Determine which specific criteria contributed most prominently to the final AIH score from a preliminary data analysis from the STOPSC database • 15 pediatric AIH patients (age 9.6 + 5.2 years) were evaluated who were diagnosed between 2002 and 2008 • 11 female, 4 male • Mean time from diagnosis to enrollment of 2.0 + 1.7 years • All had a normalized alkaline phosphatase (ALP) to alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ratio of less than 1.5 • 10/15 had autoantibody titers, including antinuclear antibody (ANA), anti-smooth muscle antibody (SMA) or liver-kidney microsomal antibody (LKM) greater than 1:80 (none had a titer less than 1:40) • 13/15 had negative viral markers • One subject had a positive HCV antibody screen and another was not evaluated) • 15/15 had no history of hepatotoxic drug use • 12/15 had both interface hepatitis and predominantly lymphoplasmacytic infiltrate receiving the maximum subscores for these criteria • 1/15 had interface hepatitis alone • 2/15 had lymphoplasmacytic infiltrate alone • None had hepatocyte rosetting • Serum globulins or IgG were measured in only 6/15 subjects, but 4 of these received maximum subscores • Antimitochondrial antibodies (AMA) as a marker for PBC were negative in 2 patients, but were not evaluated in 13/15 • 2/15 had a positive history of themselves or first-degree relative with another autoimmune disease • No patients had other defined parameters (HLA or autoantibodies) that contributed to scoring • 12/15 subjects had a cumulative score between 10 and 15 (13.3 + 1.7) consistent with probable AIH • 3/15 had a score > 15 (16.3 + 0.6) consistent with definite AIH ABSTRACT #1624 Use of International Autoimmune Hepatitis (AIH) Group Criteria for Pediatric Patients in a North American Primary Sclerosing Cholangitis (PSC)/AIH Registry (STOPSC) DD Black1,3, R Anand2, W Yin2, GL Whitington3 and the STOPSC Research Group 1Pediatrics, University of Tennessee Health Science Center, Memphis TN, 2the EMMES Corporation, Rockville, MD and 3Le Bonheur Children’s Medical Center, Memphis, TN Studies of Primary Sclerosing Cholangitis (STOPSC) is a registry of adults and children with PSC, PSC/AIH overlap and AIH (children only) that includes 10 adult and 10 pediatric hepatology programs in 13 centers in the US and Canada. Pediatric patients (less than 18 yrs of age) with AIH are included in the registry to enable study of the relationships among adult and pediatric PSC, PSC/AIH overlap and pediatric AIH. Children with AIH are evaluated at entry using criteria established by the International AIH Group (IAIHG) (Alvarez et al, Journal of Hepatology 31:929-938, 1999). Subjects were recruited between September, 2007 and May, 2008 with an average time from diagnosis to enrollment of 2.0+1.7 yrs. Data were analyzed to determine which specific criteria contributed most prominently to the final AIH score. Fifteen pediatric AIH patients (age 9.6+5.2 yrs) were evaluated. Eleven were female, all had an alkaline phosphatase (ALP) to alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ratio of less than 1.5, 10/15 subjects had autoantibody titers, including antinuclear antibody (ANA), anti-smooth muscle antibody (SMA) or liver-kidney microsomal antibody (LKM), greater than 1:80 (none had a titer less than 1:40), 13/15 had negative viral markers (one subject had a positive HCV antibody screen and another was not evaluated), 15/15 had no hepatotoxic drug use, 12/15 had both interface hepatitis and predominantly lymphoplasmacytic infiltrate (1/15 had interface hepatitis alone, 2/15 had lymphoplasmacytic infiltrate alone, and none had hepatocyte rosetting), thus receiving the maximum subscores for these criteria. Serum globulins or IgG were measured in only 6/15 subjects, but 4 of these received maximum subscores. Antimitochondrial antibodies as a marker for PBC were negative in two patients but were not evaluated in 13/15. Only 2/15 subjects had a history of themselves or first-degree relative with another autoimmune disease. None had other defined parameters (HLA or autoantibodies) that contribute to scoring. 12/15 subjects had a cumulative score between 10 and 15 (13.3+1.7), consistent with probable AIH, and 3/15 had a score >15 (16.3+0.6), consistent with definite AIH. These preliminary results suggest that the IAIHG criteria are suitable as eligibility criteria for pediatric AIH patients entering a multicenter registry. More widespread measurement of serum globulins and IgG would likely increase overall scores. STOPSC enrollment is ongoing, and subjects will be followed longitudinally on an annual basis. (Sponsored by the Morgan Foundation and PSC Partners) INCLUSION OF PEDIATRIC PATIENTS WITH AIH • Subjects less than 18 years of age • Retrospective recruitment with diagnosis of AIH within the past five years, as well as prospective recruitment • Clinical and laboratory data collected at diagnosis and then annually • Subjects recruited between September, 2007 and May, 2008 INTERNATIONAL AUTOIMMUNE HEPATITIS GROUP SCORING • Evaluated at entry using criteria established by the International AIH Group (IAIHG) (Alvarez et al, Journal of Hepatology, 31:929-938, 1999) • Weighted scoring based on: • Sex • ALP/ALT or AST ratio after dividing values by the ULN for each test • Serum globulins or IgG above normal • Presence of autoantibodies • Absence of AMA (PBC marker), viral markers, and hepatotoxic drug history • Liver histology (interface activity, lymphoplasmacytic infiltrate, hepatocyte rosetting, absence of biliary changes) • Other autoimmune disease in patient or first degree relative • Optional • Presence of other defined autoantibodies (pANCA, anti-LC1, anti-SLA, anti-ASGPR, anti-LP, or anti-sulfatide) • HLA DR3 or DR4 • Response to treatment not used • Score stratification • > 15 Definite AIH • 10-15 Probable AIH BACKGROUND STUDIES OF PRIMARY SCLEROSING CHOLANGITIS (STOPSC) • North American registry of adults and children with: • PSC • PSC/autoimmune hepatitis (AIH) overlap • AIH (children only) • 10 adult and 10 pediatric hepatology programs in 13 major medical centers in the US and Canada • Children included to enable study of the relationships among adult and pediatric PSC, PSC/AIH overlap, and pediatric AIH CONCLUSIONS • These preliminary results suggest that the IAIHG criteria are suitable as eligibility criteria for pediatric AIH patients entering a multicenter registry • More widespread measurement of serum globulins and IgG would likely increase overall scores • STOPSC enrollment is ongoing, and subjects will be followed longitudinally on an annual basis Sponsored by the Morgan Foundation and PSC Partners Seeking a Cure Interface activity with lymphoplasmacytic infiltrate (arrows point to plasma cells) Moderate interface hepatitis Photomicrographs by Pamela B. Sylvestre, MD