Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis

Minoru Nakamura; Hisayoshi Kondo; Atsushi Tanaka; Atsumasa Komori; Masahiro Ito; Kazuhide Yamamoto; Hiromasa Ohira; Mikio Zeniya; Etsuko Hashimoto; Masao Honda; Shuichi Kaneko; Yoshiyuki Ueno; Kentaro Kikuchi; Shinji Shimoda; Kenichi Harada; Kuniaki Arai; Yasuhiro Miyake; Masanori Abe; Makiko Taniai; Toshiji Saibara; Shotaro Sakisaka; Hajime Takikawa; Morikazu Onji; Hirohito Tsubouchi; Yasuni Nakanuma; Hiromi Ishibashi

doi:10.1111/hepr.12423

Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis

Hepatol Res. 2015 Aug;45(8):846-55. doi: 10.1111/hepr.12423. Epub 2014 Dec 11.

Authors

Minoru Nakamura^{1

2}, Hisayoshi Kondo³, Atsushi Tanaka⁴, Atsumasa Komori¹, Masahiro Ito¹, Kazuhide Yamamoto⁵, Hiromasa Ohira⁶, Mikio Zeniya⁷, Etsuko Hashimoto⁸, Masao Honda⁹, Shuichi Kaneko⁹, Yoshiyuki Ueno¹⁰, Kentaro Kikuchi¹¹, Shinji Shimoda¹², Kenichi Harada¹³, Kuniaki Arai⁹, Yasuhiro Miyake⁴, Masanori Abe¹⁴, Makiko Taniai⁸, Toshiji Saibara¹⁵, Shotaro Sakisaka¹⁶, Hajime Takikawa⁴, Morikazu Onji¹⁴, Hirohito Tsubouchi¹⁷, Yasuni Nakanuma¹³, Hiromi Ishibashi¹

Affiliations

¹ Clinical Research Center in National Hospital Organization (NHO) Nagasaki Medical Center and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan.
² Headquaters of gp210 working in Intractable Hepatobiliary Disease Study Group supported by the Ministry of Health, Labor and Welfare of Japan, Tokyo, Japan.
³ Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
⁴ Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
⁵ Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁶ Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
⁷ Division of Gastroenterology and Hepatology, Tokyo Jikei University School of Medicine, Tokyo, Japan.
⁸ Department of Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
⁹ Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
¹⁰ Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
¹¹ Department of Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki, Japan.
¹² Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
¹³ Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
¹⁴ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan.
¹⁵ Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
¹⁶ Department of Gastroenterology and Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
¹⁷ Department of Digestive and Lifestyle-related Disease, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan.

PMID: 25220608
DOI: 10.1111/hepr.12423

Abstract

Aim: The aim of the present study is to evaluate the factors influencing biochemical response to treatment and the value of biochemical response for predicting long-term outcomes in Japanese patients with primary biliary cirrhosis (PBC).

Methods: Biochemical response to ursodeoxycholic acid (UDCA) or UDCA plus bezafibrate was defined as good (≤upper limit of normal [ULN]), fair (≤1.5 × ULN) or poor (>1.5 × ULN) at 2 years after initiation of UDCA treatment. Associations between various factors (including age, sex, autoantibody status and histological variables at baseline), biochemical response to treatment and long-term outcomes were evaluated in 164 Japanese PBC patients.

Results: Anti-gp210 positivity and a higher bile duct loss score were significant risk factors for worse alkaline phosphatase (ALP) response (odds ratios [OR], 2.78 and 1.85, respectively). Age, anti-gp210 positivity and anticentromere positivity were significant risk factors for worse alanine aminotransferase (ALT) response (OR, 1.05, 4.0 and 2.77, respectively). Anti-gp210 positivity and a higher hepatitis score were significant risk factors for worse immunoglobulin (Ig)M response (OR, 2.10 and 2.06, respectively). Worse ALP and IgM response were significant risk factors for progression to late-stage disease without jaundice (OR, 2.27 and 2.32, respectively). Worse ALT response was a significant risk factor for progression to late-stage disease with persistent jaundice (OR, 11.11).

Conclusion: Biochemical response to treatment at 2 years, which is influenced by autoantibody status and histological variables at baseline, can predict long-term outcomes in Japanese patients with PBC.

Keywords: anti-gp210 antibody; anticentromere antibody; bezafibrate; biochemical response to treatment; histological staging and grading for primary biliary cirrhosis; ursodeoxycholic acid.