Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis

Yasuhiro Miyake, Yoshiaki Iwasaki, Haruhiko Kobashi, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Ryoichi Okamoto, Kouichi Takaguchi, Hiroshi Ikeda, Yasuhiro Makino, Masaharu Ando, Kohsaku Sakaguchi, Kazuhide Yamamoto

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Aim: 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.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalHepatology Research
Issue number3
Publication statusPublished - 2009


  • Acute hepatitis
  • Antinuclear antibody
  • Autoimmune hepatitis
  • Immunoglobulin G

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases


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