Refractory autoimmune hepatitis in children: Considerations for assessment and management

Figure 1 Algorithm for the evaluation of children with autoimmune hepatitis not responding to or intolerant to first-line treatment. AIH: Autoimmune hepatitis; ESPGHAN: European Society of Pediatric Gastroenterology, Hepatology and Nutrition; ANA: Antinuclear antibody; SMA: Smooth muscle antibody; LKM-1: Liver kidney microsomal antibody type 1; LC-1: Liver cytosol antibody type 1; SLA: Soluble liver antigen; pANCA: Perinuclear antineutrophil cytoplasmic antibody; IgM: Immunoglobulin M; DNA: Deoxyribonucleic acid; PCR: Polymerase chain reaction; RNA: Ribonucleic acid; TSH: Thyrotropin; MRCP: Magnetic resonance cholangiopancreatography.

Figure 2 Histopathology of autoimmune hepatitis in a 13-year-old patient with good compliance on azathioprine but with mildly elevated aminotransferases (55-70 IU/L; upper limit of normal 40 IU/L) and immunoglobulin G (17 g/L; upper limit of normal 16 g/L). A and B: Classical features of autoimmune hepatitis in the index biopsy showing lymphoplasmacytic infiltrate affecting both portal and perivenular regions; C: Interface hepatitis with emperipolesis and hepatocyte resetting. Hematoxylin-eosin original magnifications, × 100, × 200, × 200; D and E: Follow-up biopsy demonstrating ongoing portal infiltrate with an interface component; F: Resolution of acute necro-inflammatory and perivenular inflammation, leaving bridging fibrosis. Hematoxylin-eosin original magnifications × 100, × 100, Haematoxylin van Gieson × 40.

Figure 3 Sequential liver biopsies in a patient with refractory autoimmune hepatitis with a change of phenotype to primary sclerosing cholangitis over time. A: Index biopsy showing features compatible with autoimmune hepatitis; portal plasma cell-rich infiltrate with interface hepatitis; B: Perivenular infiltrate with hepatocyte dropout [A and B: Hematoxylin-eosin (HE) × 200]; C: Early bridging fibrosis was present at time of index biopsy (Masson trichrome × 40); D and E: Follow-up biopsy after 10 years; resolution of inflammation (D) (HE × 40); subtle biliary features with an “onion skin” sclerosing bile duct lesion (E) (HE × 200); F: Sclerosing bile duct on collagen stain (Haematoxylin van Gieson × 200).

Figure 4 Suggested treatment algorithm for children with refractory autoimmune hepatitis. ¹If mycophenolate mofetil used as second line agent. ²In children with concomitant type 1 diabetes mellites. Modified from Mack et al[2] and Mieli-Vergani et al[37].