This cross-sectional study compared the 2008 criteria for diagnosing AIH with the 1999 revised original criteria in a pediatric cohort with liver disease. We showed that the 2008 simplified criteria are useful for pediatric patients. Prior studies evaluated these criteria compared to codified descriptive criteria first developed by the IAIHG in 1993.2–6
While all of our AIH subjects met the diagnostic criteria based on the 1993 criteria, we chose to use the 1999 original revised criteria as our “gold standard” due to its established use in clinical and research settings and the validation of this criteria in the pediatric population9
. Despite the relatively small sample size used in this study, we demonstrated excellent sensitivity and specificity of the 2008 criteria compared to the 1999 criteria consistent, with the results seen in adult studies.
We also showed that either IgG or serum globulin could be used to diagnose AIH in children. The 1993 and 1999 criteria used serum globulin and IgG levels interchangeably.1,2
Correlation between serum globulin levels and IgG have been previously established in patients with chronic liver disease.13
Hennes et al. discussed the use of IgG versus gamma globulin and found that there was a close correlation between the two (Pearson coefficient: r = 0.87).3
They chose to use IgG alone in their analysis due to many missing gamma globulin levels in their cohort. Missing data is frequent in many studied and this was also true of our population. For this reason, we validated the 2008 criteria using IgG levels first then using either IgG or serum globulins to determine the utility of both criteria. We found that calculating the simplified score using serum globulins was equally effective as using IgG and may be used when IgG is not available.
One limitation is that the 2008 criteria do not reliably identify patients presenting in FHF due to AIH. The 1999 criteria should be used to confirm the diagnosis of AIH in these patients. In our cohort we found that 4 out of 5 AIH patients presenting in FHF had normal IgG levels and 3 out of 5 had normal serum globulin levels. Yeoman et al also found this in an adult population and were cautious to note that both the 1999 and 2008 criteria were not developed with FHF in mind.5
In addition, there could be selection bias in the selection of non-AIH patients. Nearly 200 charts of non-AIH patients were reviewed to find sufficient that included all the required data to calculate 1999 and 2008 scores. These patients may have differed from those not included in that they had a more extensive evaluation than those with more readily diagnosed non-AIH disease.
Another concern is that of diagnosing children with other autoimmune liver diseases. Due to the retrospective nature of our study, we recognize that our study likely did not identify all the patients with autoimmune sclerosing cholangitis at diagnosis. We identified only one subject who presented with an AIH/PSC overlap syndrome. Gregorio et al found that 50% of patients with characteristics diagnostic of AIH actually had bile duct disease at presentation, diagnosed by cholangiography.14
Diagnostic guidelines from the American Association of the Study of Liver Diseases now include the need for cholangiographic evaluation in children at the time of diagnosis.15,16
We reviewed all available cholangiograms that were subsequently performed on our AIH patients and all 8 yielded normal results with no bile duct abnormalities. In our cohort 3 out of 8 subjects with PSC were diagnosed with “probably AIH” using the 2008 simplified criteria. All of the PSC patients had biliary tract changes on their pathology and abnormal cholangiograms or magnetic resonance cholangiopancreatography indicative of PSC. While a score of 6 inaccurately diagnoses these patients as having “probable AIH” and decreases the specificity of the 2008 criteria, the clinical diagnosis and management should be guided by the biopsy results and not the score alone. Ebbeson suggested that replacing alkaline phosphatase ratio with GGT ratio in the IAIHG score may identify better those children with biliary disease9
. Studies evaluating the IAIHG scoring systems in patients with PSC and overlap syndromes show that the revised original criteria and the simplified criteria have similar specificity in these patients.17–19
In conclusion, the 2008 diagnostic criteria for AIH have excellent sensitivity and specificity when used in a pediatric cohort, except in those AIH patients with FHF. Since there are only 4 variables to consider in the calculation of the 2008 diagnostic criteria, it is easier to use in a clinical setting compared with the 1999 system. However, cholangiographic studies should be performed in all children with AIH to exclude PSC.16
Serum globulin levels and IgG can be used interchangeably and can be used when IgG levels have not been obtained. The sensitivity and specificity in our pediatric cohort were similar to what has been reported in the adult population.