Diagnosing AIH in Children: Is the International AIH Group Scoring System Useful?Ebbeson RL, Schreiber RA. Clin Gastroenterol Hepatol 2004;2:935-940.
In 1992, the International Autoimmune Hepatitis Group developed a scoring system for adults to differentiate autoimmune hepatitis from other causes of chronic liver disease (1). In the present study, Ebbeson and Schreiber investigated the possibility that a modification of this system could be applied to children both to diagnose autoimmune hepatitis and to distinguish them from children with biliary features or “overlap syndrome.” The authors retrospectively applied the International Autoimmune Hepatitis Group scoring system to 28 children with a diagnosis of chronic immune liver disease (21 with autoimmune hepatitis, 4 with isolated sclerosing cholangitis and 3 with overlap syndrome). A diagnosis of overlap syndrome was made when the patient had not only the clinical and histologic findings of autoimmune hepatitis but also findings of sclerosing cholangitis on cholangiography.
The authors found that 18 of 21 patients with autoimmune hepatitis scored were identified as “definite” autoimmune hepatitis (>15 points) and the other three as “probable” (10 to 15 points). Four patients with primary sclerosing cholangitis were identified as “other” (<10 points) and three with overlap syndrome were identified as “definite” autoimmune hepatitis. It was noted that removing the two points allocated for <25 g daily alcohol intake did not alter the classification of the patients either before or after treatment in any way. The authors state that in growing children, gamma-glutamyl transaminase is a more specific marker of cholestatic liver disease than alkaline phosphatase, as the latter may reflect bone activity. When gamma-glutamyl transaminase was substituted for alkaline phosphatase in the item of the scoring system comparing the ratio of alkaline phosphatase to aspartate aminotransferase, five patients who scored “definite” for autoimmune hepatitis by the original system were reclassified as “probable” autoimmune hepatitis. Four of these five patients had incomplete response to treatment. Of the five reclassified as “probable” autoimmune hepatitis, two had sclerosing cholangitis confirmed by endoscopic retrograde cholangiopancreatography and a diagnosis of overlap syndrome, one had biliary changes on ultrasound and was awaiting cholangiography, one had inconclusive changes on endoscopic retrograde cholangiopancreatography because of incomplete filling of the biliary tree (follow-up liver biopsy showed biliary changes) and the last did not have cholangiographic studies performed (young age and complete response to treatment). Ebbeson and Schreiber concluded this paper by endorsing the modified International Autoimmune Hepatitis Group scoring system in the diagnosis of autoimmune hepatitis in children.
The scoring system for autoimmune hepatitis studied in this paper was first proposed in 1992 by an international panel of experts (the International Autoimmune Hepatitis Group) (1). The need for clear diagnostic criteria for what was then known as chronic active hepatitis was heightened by the identification of the hepatitis C virus in 1989 (2). The scoring system was constructed on clinical and biochemical parameters characteristic of autoimmune hepatitis. In the original scoring system, points were assigned for “minimal” parameters of (i) female gender, (ii) hepatitic biochemical profile, (iii) hyperglobulinemia, (iv) increased autoantibody titers, (v) absence of viral hepatitis markers, (vi) family history of autoimmunity and (vii) absence of drug or alcohol ingestion. Additional parameters included (i) characteristic histology, (ii) genetic factors and (iii) response to immunosuppressive therapy. A pretreatment aggregate score of >15 was designated “definite” and scores between 10-15 “probable” autoimmune hepatitis. Post-treatment scores >17 were designated “definite” and scores of 12 to 17 “probable” autoimmune hepatitis, respectively (1).
Several groups (2,3) have attempted to validate the International Autoimmune Hepatitis Group scoring system. In one pediatric study, when the original scoring system was applied retrospectively to 52 children with a diagnosis of untreated autoimmune hepatitis, 35 (67%) scored as definite autoimmune hepatitis and the remaining 17 as probable autoimmune hepatitis (4). While on treatment, 10 more patients fulfilled criteria for definite autoimmune hepatitis. As 86% of 52 children could be designated as definite autoimmune hepatitis and the remaining probable autoimmune hepatitis, the authors felt that the scoring system could be applied to the pediatric age group. The diagnostic criteria were reviewed and modified in 1999 (5). The principal changes related to the alkaline phosphatase:aspartate aminotransferase ratio, drug history, liver histology and response to treatment. To increase weighting against biliary disease, the negative score for anti-mitochondrial antibody epositivity was increased from −2 to −4 and the score for histologic evidence of bile duct damage was increased from −1 to −3. Because interface hepatitis is particularly characteristic of autoimmune hepatitis, a score of −5 was allocated to those who did not have this feature. As classic autoimmune hepatitis does not always respond to treatment, it was decided to remove points for “no response,” “treatment failure” or “partial response.” It was also noted that because low titers of antibodies may be significant in children, the previous specification for autoantibody titers was not a significant factor in childhood scoring. In consideration of the importance of correct identification of autoantibodies both in diagnosis and in monitoring disease activity, a committee was formed to work towards standardization of methodology and data collection on the sensitivity and specificity of various assay systems (6).
The overlap between sclerosing cholangitis and autoimmune hepatitis has been a matter of controversy, and several groups have used the scoring system to better delineate this group of patients. Boberg et al. used the original scoring system to evaluate 114 primary sclerosing cholangitis patients in Norway and reported that two primary sclerosing cholangitis patients (1.8%) fulfilled criteria for “definite” and 38 (33%) fulfilled criteria for “probable” autoimmune hepatitis (7). After the criteria were modified, the modified scoring system was applied to the same group of primary sclerosing cholangitis patients. Reanalysis showed that of the 38 (33.3%) originally classified as probable, only 10 (8.8%) remained in this category, giving an overall specificity of 89.5% for exclusion of autoimmune hepatitis in this group of primary sclerosing cholangitis patients (1). Chazouilleres and colleagues evaluated four groups (7-10) using the scoring system and reported that the modified system was more specific in diagnosing the overlap syndrome (11). In pediatrics, Gregorio et al. investigated whether sclerosing cholangitis with an autoimmune serology and autoimmune hepatitis are distinct entities (12). Overall, 25 (89%) patients with autoimmune hepatitis and 15 of 23 (65%) with autoimmune sclerosing cholangitis would have been diagnosed as definite autoimmune hepatitis post-treatment (P = 0.041) by using the scoring criteria (12). The difference in the adult studies and the pediatric study could be explained by the inclusion criteria. In the adult studies, any patient with cholangiographic changes of sclerosing cholangitis was included, whereas in the pediatric study only those with both autoantibodies and characteristic changes on cholangiography were included.
The International Autoimmune Hepatitis Group scoring system is not used commonly in pediatric clinical practice. The study of Ebbeson and Schreiber may persuade some readers to do so in children with a complicated presentation. The studies discussed above demonstrate that the International Autoimmune Hepatitis Group scoring system can effectively separate autoimmune hepatitis from isolated sclerosing cholangitis while highlighting the difficulty in identifying those with overlap between autoimmune hepatitis and sclerosing cholangitis. The current study, though retrospective and with small sample size, is novel in that by substituting gamma-glutamyl transferase for alkaline phosphatase, Ebbeson and Schreiber have tried to identify the overlap group. The basis for making this change appears appropriate given that alkaline phosphatase is affected by bone activity especially in a growing child (13). In routine clinical practice, the majority of children with autoimmune hepatitis are likely to be assigned to the “definite” group. Those who are designated as ‘probable’™ are more likely to have biliary features and comprise the overlap group. Problems with sedation for imaging studies in small children and the technical expertise required to perform endoscopic retrograde cholangiopancreatography have limited the use of this diagnostic test. The scoring system may help limit biliary imaging studies to those with overlap features whose scores indicate “probable” autoimmune hepatitis. This group of children might benefit from addition of ursodeoxycholic acid to the immunosuppressive regimen. The usefulness of the International Autoimmune Hepatitis Group scoring system has also been recently illustrated by Bridoux-Henno et al. in diagnosing autoimmune hepatitis when the sole antibody present was anti-liver cytosol antibody (14).
In conclusion, the international scoring system has a place in confirming the diagnosis of autoimmune hepatitis in cases with a complicated clinical presentation. The scoring system also provides a means of comparison between different centers in different parts of the world.
Assistant Professor Division of Pediatric Hepatology Recanati Miller Transplant Institute, Mount Sinai Medical Center New York, New York
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