between the ages of 10 and 20 and 45 and 70 years and has To determine the clinical, biochemical, and histologia relatively benign course at least in adults, 3 whereas LKMcal features, and outcome of childhood autoimmune 1 positive patients have a more severe disease with progreshepatitis (AIH), we reviewed the medical records of 52 sion to cirrhosis despite immunosuppressive treatment. 3,4 children with AIH, 32 (median age: 10 [2-15] years) anti-When compared with human leukocyte antigen (HLA) DR-4 nuclear and/or smooth muscle antibody (ANA/SMA) posipositive subjects, patients with AIH that are HLA DR-3 positive, 20 (7 [0.8-14] years) liver/kidney microsomal antitive are more likely to present at an earlier age, to relapse body (LKM-1) positive, with median follow-up of 5 years on immunosuppressive treatment and to require liver trans-(range 0.3-19). At presentation: 56% had symptoms of proplantation. 5 In the only large series of children with AIH longed acute hepatitis; LKM-1 positive were younger published, 6 a similarly severe disease was reported in ANA/ (P Γ
.011), with higher bilirubin (P Γ
.007), and AST (P SMA positive and LKM-1 positive patients. No study has Γ
.047); ANA/SMA positive had lower albumin (P Γ
.023); attempted to identify factors predictive of long-term outcome. 69% ANA/SMA positive, and 38% LKM-1 positive were In the present study we have compared the clinical, biochemicirrhotic (P Γ
.080). ANA/SMA positive had increased frecal, and histological features and outcome of children with quency of HLA haplotype A1/B8/DR3/DR52a compared ANA/SMA positive or LKM-1 positive AIH, by reviewing the with controls (53% vs. 14%, P Γ΅ .001). Of six (5 LKM-1 medical records of 52 consecutive patients diagnosed in our positive) with fulminant hepatitis, four were transcenter over a period of 20 years. planted, one died, and one ANA/SMA positive improved with immunosuppression. Of 47 treated with immuno-
PATIENTS AND METHODS suppression, 2 (1 LKM-1 positive) died with no remission and 4 (2 LKM-1 positive) were transplanted 8 to 14 years Between 1973 and 1993, a total of 73 children with autoimmune after diagnosis. Immunosuppression was stopped sucliver disease, defined as the presence of clinical and/or biochemical cessfully in 19% of ANA/SMA positive after a median of evidence of liver disease and serological features of autoimmunity 3 years of treatment, but in none of LKM-1 positive. Basein the absence of a known cause, were referred to the Pediatric Liver line bilirubin and international normalized prothrom-Unit of King's College Hospital. Computerized recording of referred bin ratio (INR) were independent variables predictive cases started in 1991. Of 822 children with liver disease older than 4 months referred between 1991 and 1993, 19 had autoimmune liver of outcome. In conclusion, ANA/SMA positive and LKMdisease, giving a relative incidence of 2.3%. 1 positive AIH in childhood have clinical, biochemical, Of the 73 children, 20 with ANA/SMA positive sclerosing cholangiand histological differences, but similar severity and tis, diagnosed on the basis of characteristic bile duct changes on long-term outcome. (HEPATOLOGY 1997;25:541-547.)
cholangiography 7 and one with antimitochondrial antibody positive AIH were excluded from this analysis, leaving a total of 52 children Autoimmune hepatitis (AIH) is a progressive inflammatory with ANA/SMA positive or LKM-1 positive AIH. Ten of these 52 patients were diagnosed between 1991 and 1993 giving a relative liver disease characterized histologically by dense mononuincidence of 1.2%. The AMA positive patient was a 12-year-old girl clear cell infiltrates in the portal tracts and serologically by whose AMA was M2 specific and reactive to pyruvate dehydrogethe presence of nonorgan and liver specific autoantibodies in nase. 8,9 During a 12-year follow-up, she underwent six liver biopsy the absence of a known etiology. 1 The disease is rare and in procedures that showed features of periportal/periseptal hepatitis childhood is associated with either the nuclear and/or smooth with no evidence of bile duct damage. She went into remission with muscle antibody (ANA/SMA) or with the liver kidney microprednisolone and azathioprine treatment but died at the age of 24 somal type 1 antibody (LKM-1) in serum. 2 years with decompensated cirrhosis.
Reports including both adults and children with AIH sug-
Of the 52 children with AIH, 32 were ANA/SMA positive (24 girls; gest that ANA/SMA positive AIH has two peaks of incidence median age: 10.5, range 2.3-14.9 years). At presentation, four chil-