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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
The following people have nothing to disclose:
Dennis D. Black
Ravinder Anand
Wanrong Yin
Gene L. Whitington
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)
PURPOSE
• To determine the utility of the AIH diagnostic criteria established by the
International AIH Group (IAIHG) (Alvarez et al, Journal of Hepatology, 31:929938, 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
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
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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
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Response to treatment not used
• Score stratification
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• North American registry of adults and children
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> 15 Definite AIH
10-15 Probable AIH
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
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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
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with:
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(IAIHG) (Alvarez et al, Journal of Hepatology, 31:929-938, 1999)
• Weighted scoring based on:

STUDIES OF PRIMARY SCLEROSING
CHOLANGITIS (STOPSC)
• 15 pediatric AIH patients (age 9.6 + 5.2 years) were
• Evaluated at entry using criteria established by the International AIH Group

BACKGROUND
RESULTS
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
CONCLUSIONS
PSC
PSC/autoimmune hepatitis (AIH) overlap
AIH (children only)
• 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
• 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
Moderate interface hepatitis
Photomicrographs by Pamela B. Sylvestre, MD
Interface activity with lymphoplasmacytic
infiltrate (arrows point to plasma cells)
Sponsored by the Morgan Foundation and PSC
Partners Seeking a Cure