See “Autoimmune Hepatitis in Children in Eastern Denmark” by Vitfell-Pedersen et al on page 376.
Autoimmune hepatitis (AIH) may be particularly aggressive in children and induce severe liver damage, if untreated. On the contrary, immunosuppressive therapy, with prednisolone alone or in combination with azathioprine, leads to remission in 80% of cases resulting in a normal life expectancy, good quality of life (1), and a transplant-free survival rate of 90% (2).
In this issue of JPGN, Vitfell-Pedersen et al report the features and long-term outcome of children with AIH enrolled in a paediatric population-based survey from the eastern part of Denmark (3). This retrospective study, if compared with previous European series, shows some unusual findings such as male preponderance, extremely low rate of anti-liver kidney microsomal type 1 antibody–positive patients, and absence of fulminant cases (4,5). Despite these peculiarities, which could be due to bias of the study, it is noteworthy that liver cirrhosis, present in 69.6% of patients at diagnosis, did not affect either the overall survival or the survival free of liver transplantation.
This favourable outcome could suggest the possibility, reported in the literature, but still a matter of debate among experts, of reversibility of liver fibrosis in some chronic liver diseases (6,7). Obviously, this is a simple hypothesis because histological evaluation of the liver was not performed in Danish patients with sustained biochemical remission.
Another relevant finding of the Danish study is that 84% of patients achieved remission in a median of 5.4 months from the start of treatment (60.6% on treatment with prednisolone and azathioprine and 24% on prednisolone alone). Consequently, treatment with prednisolone and azathioprine seemed to be more effective than prednisolone alone in inducing remission. Unfortunately, the authors did not clarify why a single treatment schedule was not used and azathioprine added only to some patients (poor control of transaminases, steroid adverse effects?) or why so many patients were not controlled by treatment. At the end of follow-up, 15% of the patients were in stable remission and off therapy. Even for this issue, no information about the putative predictors of such a good outcome was provided. Actually, despite the availability of many studies and guidelines for AIH (8), many aspects concerning children with AIH remain unclear. In this context, it would have been useful to have more details about clinical features of patients treated with steroid alone versus those treated with steroid and azathioprine, doses of immunosuppressant drugs during the different phases of the treatment, duration of each phase, and minimum required doses to maintain remission to draw conclusions about the best mode of treatment for AIH in children.
Other limitations of the study are represented by the scarce use of the available autoantibody repertoire for the diagnosis of AIH (8,9) absence of indication of the autoantibodies’ serum levels considered positive for children (8), and limited use of cholangiography, which was not performed in all children with AIH to exclude biliary involvement according to American Association for the Study of Liver Diseases guidelines (8).
Even with these limitations, we think that Vitfell-Pedersen study is valuable because it draws attention to many unclarified points of AIH in childhood. To date, because of the relative rarity of this condition, in common clinical practice the management of children with AIH often reflects the preferences of individual centres (8). It is probably time to initiate large multicentre prospective studies to reach common agreement on the management of children with AIH.
1. Mieli-Vergani G, Vergani D. Autoimmune liver diseases in children—what is different from adulthood? Best Pract Res Clin Gastroenterol
2. Saadah OI, Smith AL, Hardikar W. Long-term outcome of autoimmune hepatitis in children. J Gastroenterol Hepatol
3. Vitfell-Pedersen J, Jørgensen MH, Müller K, Heilmann C. Autoimmune hepatitis in children in eastern Denmark. J Pediatr Gastroenterol Nutr
4. Gregorio GV, Portmann B, Reid F, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology
5. Gregorio GV, Portmann B, Karani J, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology
6. Friedman SL, Bansal MB. Reversal of hepatic fibrosis: fact or fantasy. Hepatology
7. Dufour JF, DeLellis R, Kaplan MM. Reversibility of hepatic fibrosis in autoimmune hepatitis. Ann Intern Med
8. Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis. Hepatology
9. Bogdanos DP, Mieli-Vergani G, Vergani D. Autoantibodies and their antigens in autoimmunet hepatitis. Semin Liver Dis