title: Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis.
abstract: OBJECTIVE
  Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20-30% of patients are negative for ANA. We assessed the clinical features of ANA-negative patients.
  
  
  METHODS
  A retrospective analysis was performed of 176 patients with type 1 AIH (153 females, median age 55 years). A diagnosis of AIH was made based on the revised scoring system proposed by the International Autoimmune Hepatitis Group. ANA titers were measured using a standard indirect immunofluorescence technique.
  
  
  RESULTS
  Thirty-eight patients (22%) had low titers of ANA (1:40 or 1:80), and 114 (65%) had high titers (>/= 1:160). Of 24 ANA-negative patients, 15 were positive for smooth muscle antibodies (SMA). Three of nine both ANA- and SMA-negative patients developed ANA during follow-up. The other six were diagnosed based on histological characteristics. Thirteen ANA-negative patients relapsed after the normalization of serum alanine aminotransferase (ALT) levels. ANA-negative patients more frequently showed acute presentation and, at presentation, had lower serum immunoglobulin G levels, higher serum levels of bilirubin and transaminase, and higher frequencies of histological acute hepatitis and zone 3 necrosis than those with high titers. However, the frequency of advanced stage of fibrosis was similar. The response to corticosteroids was not different among the three groups.
  
  
  CONCLUSIONS
  ANA-negative type 1 AIH shows acute-onset more frequently but may include not only acute autoimmune hepatitis, but also acute exacerbation of inactive chronic disease. Regarding the diagnosis of ANA-negative AIH, the determination of ANA during follow-up and the response to immunosuppressive treatment may be helpful.
authors.affiliation: Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kobashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yasunaka
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Okamoto
authors.forename: Kouichi
authors.initials: K
authors.lastname: Takaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Makino
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ando
authors.forename: Kohsaku
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto