Autoimmune hepatitis in patients with multiple sclerosis: The role of immunomodulatory treatment

Clin Res Hepatol Gastroenterol. 2019 Jun;43(3):e25-e32. doi: 10.1016/j.clinre.2018.12.002. Epub 2018 Dec 26.

Abstract

Background: Development of autoimmune hepatitis (AIH) has been sporadically reported in patients with multiple sclerosis (MS) either concurrently or after treatment with immunomodulatory drugs, including interferon-beta (IFN-β) and steroids.

Aim: To report a large cohort of 14 patients with MS diagnosed with AIH during an assessment of deranged liver function tests (LFTs).

Patients and methods: From 2005 to 2017, we prospectively identified 14 (13 women) patients with MS who suffered also from AIH after investigation in our department for the presence of deranged LFTs. Age at diagnosis of MS was 36.7 ± 9.3 years while at diagnosis of AIH 43.1 ± 12 years.

Results: AIH diagnosis was based on elevation of aminotransferases in all patients [alanine aminotransferase: 520 IU/L (range: 115-1219)], elevation of IgG in 6, compatible autoantibody profile in all, including 5 patients with liver-specific autoantibodies and typical or compatible histological features in 11 patients. 5 patients were under treatment with IFN-β plus methylprednisolone pulses, 3 with IFN-β plus oral steroids, 1 with IFN-β, 4 with methylprednisolone pulses whereas 1 patient was free of treatment. The median time from IFN-β initiation to the development of hepatitis was 12 months (range:1-120). Treatment for AIH was initiated in 13 patients with prednisolone (0.5-1 mg/kg/day) plus mycophenolate myfetil (2 g/day) in 10 and prednisolone plus azathioprine in 3 with complete and partial response in 11 and 2 patients, respectively.

Conclusions: The differential diagnosis of hepatitis in MS patients should include AIH and in particular when immunomodulatory treatment has been preceded. Autoantibody testing and liver histology play fundamental role in establishing a prompt diagnosis of AIH in these patients. Treatment of AIH in patients with MS seems safe and efficient as complete or partial response was recorded in all of our patients.

Keywords: Autoimmune hepatitis; IFN-β; Immunomodulatory treatment; Multiple sclerosis.

MeSH terms

  • Adult
  • Autoantibodies / blood
  • Azathioprine / therapeutic use
  • Female
  • Glucocorticoids / therapeutic use
  • Hepatitis, Autoimmune / diagnosis*
  • Hepatitis, Autoimmune / drug therapy
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Interferon-beta / therapeutic use
  • Liver Function Tests
  • Male
  • Methylprednisolone / therapeutic use
  • Multiple Sclerosis / complications*
  • Mycophenolic Acid / therapeutic use
  • Prednisolone / therapeutic use

Substances

  • Autoantibodies
  • Glucocorticoids
  • Immunologic Factors
  • Immunosuppressive Agents
  • Interferon-beta
  • Prednisolone
  • Mycophenolic Acid
  • Azathioprine
  • Methylprednisolone