Overlap autoimmune hepatitis and primary sclerosing cholangitis in a patient with multiple sclerosis

A 16-year-old boy was diagnosed from multiple sclerosis (MS) after suffering from paresthesia in upper limbs and VI cranial nerve paresis. Corticosteroids and fingolimod were started. After 13 months a worsening of liver biochemical tests (LBT) was noticed: ALP 787 U/L, GGT 737 U/L, AST 195, ALT 321, Bi 0.5 mg/dL, so fingolimod was stopped. Serologies were negative, thyroid function, Alpha-1-antitrypsin, ceruloplasmin, and iron metabolism tests were normal. He had ANA 1/320 and c-ANCA positive autoantibodies. After 3 months there was no improvement of LBT: ALP 726 AST 87 ALT 95 GGT 515 Bi 0.7. After an elevation of IgG (18,23g/L), a liver biopsy (LB) and a magnetic resonance cholangiography (MRC) were performed, being diagnosed from small duct Primary Sclerosing Cholangitis (PSC). A review of liver biopsy from specialized pathologists was requested, showing changes consistent with overlap autoimmune hepatitis (AIH). Ursodeoxycholic acid was initiated with decrease of AP and GGT. No treatment with corticosteroids or immunosuppressant agents were required since AST/ALT spontaneously decreased. Natalizumab was introduced with adequate control of MS. Autoimmune liver diseases are believed to have a multifactorial but unknown etiology. Studies have reported the coexistence of MS with other autoimmune diseases (AD) 1. Drug toxicity (DILI) is becoming a relatively important cause of liver altered tests given emerging therapies used as disease-modifying agents 2. In comparison to a 0.02% prevalence of AIH in general population, AIH was diagnosed in a cohort of MS in 3 out of 1800 patients (0.17%) 3. Only 1 case of MS and PSC has been reported in 2003 4. Therefore we present the first case of PSC/AIH overlap in a patient with MS so far. The existence of a previous AD in a young patient with chronic and fluctuating LBT alteration lead to the suspicion of an AILD. Some authors believe AIH/PSC-overlap might represent the same entity, described in childhood as `autoimmune sclerosing cholangitis (ASC)', with inflammatory phases of PSC manifesting earlier in the disease course as AIH and developing duct fibrosis over time 5. Treatment of MS with immunosuppressants and biologics agents such as natalizumab, might have influenced the decrease in serum transaminases due to their role in blocking leukocyte migration, which might also affect immune response in the liver.