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 journalArticle

17 Citations (Scopus)

Abstract

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
Volume39
Issue number3
DOIs
Publication statusPublished - 2009

Fingerprint

Autoimmune Hepatitis
Antinuclear Antibodies
Smooth Muscle
Serum
Antibodies
Immunosuppressive Agents
Indirect Fluorescent Antibody Technique
Transaminases
Alanine Transaminase
Bilirubin
Hepatitis
Adrenal Cortex Hormones

Keywords

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

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

Cite this

Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis. / Miyake, Yasuhiro; Iwasaki, Yoshiaki; Kobashi, Haruhiko; Yasunaka, Tetsuya; Ikeda, Fusao; Takaki, Akinobu; Okamoto, Ryoichi; Takaguchi, Kouichi; Ikeda, Hiroshi; Makino, Yasuhiro; Ando, Masaharu; Sakaguchi, Kohsaku; Yamamoto, Kazuhide.

In: Hepatology Research, Vol. 39, No. 3, 2009, p. 241-246.

Research output: Contribution to journalArticle

Miyake, Y, Iwasaki, Y, Kobashi, H, Yasunaka, T, Ikeda, F, Takaki, A, Okamoto, R, Takaguchi, K, Ikeda, H, Makino, Y, Ando, M, Sakaguchi, K & Yamamoto, K 2009, 'Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis', Hepatology Research, vol. 39, no. 3, pp. 241-246. https://doi.org/10.1111/j.1872-034X.2008.00454.x
Miyake, Yasuhiro ; Iwasaki, Yoshiaki ; Kobashi, Haruhiko ; Yasunaka, Tetsuya ; Ikeda, Fusao ; Takaki, Akinobu ; Okamoto, Ryoichi ; Takaguchi, Kouichi ; Ikeda, Hiroshi ; Makino, Yasuhiro ; Ando, Masaharu ; Sakaguchi, Kohsaku ; Yamamoto, Kazuhide. / Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis. In: Hepatology Research. 2009 ; Vol. 39, No. 3. pp. 241-246.
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T1 - Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis

AU - Miyake, Yasuhiro

AU - Iwasaki, Yoshiaki

AU - Kobashi, Haruhiko

AU - Yasunaka, Tetsuya

AU - Ikeda, Fusao

AU - Takaki, Akinobu

AU - Okamoto, Ryoichi

AU - Takaguchi, Kouichi

AU - Ikeda, Hiroshi

AU - Makino, Yasuhiro

AU - Ando, Masaharu

AU - Sakaguchi, Kohsaku

AU - Yamamoto, Kazuhide

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Acute hepatitis

KW - Antinuclear antibody

KW - Autoimmune hepatitis

KW - Immunoglobulin G

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