Early biochemical response to ursodeoxycholic acid and long-term prognosis of primary biliary cirrhosis: Results of a 14-year cohort study§

Authors

  • Li-Na Zhang,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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    • *These authors contributed equally to this work.

  • Tian-Yan Shi,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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    • *These authors contributed equally to this work.

  • Xu-Hua Shi,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Li Wang,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Yun-Jiao Yang,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Bin Liu,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Li-Xia Gao,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Zong-Wen Shuai,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Fang Kong,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Hua Chen,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Wei Han,

    1. Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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  • Shao-Mei Han,

    1. Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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  • Yun-Yun Fei,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Quan-Cai Cui,

    1. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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  • Qian Wang,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Min Shen,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Dong Xu,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Wen-Jie Zheng,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Yong-Zhe Li,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Wen Zhang,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Xuan Zhang,

    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
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  • Feng-Chun Zhang

    Corresponding author
    1. Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
    2. Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
    • Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, No. 41 Da Mu Cang, Western District, Beijing 100032, China===

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    • fax: +86-10-6915-8799


  • Potential conflict of interest: Nothing to report.

  • This work was supported by grants from the National Science Technology Pillar Program in the 11th Five-Year Plan (2008BAI59B03), the National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2012ZX09303006-002), and the Research Special Fund for Public Welfare Industry of Health (201202004).

Abstract

The biochemical response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis is a strong predictor of long-term outcome and thus facilitates the rapid identification of patients needing new therapeutic approaches. Numerous criteria for predicting outcome of treatment have been studied based on biochemical response to UDCA at 1 year. We sought to determine whether an earlier biochemical response at 3 or 6 months could as efficiently identify patients at risk of poor outcome, as defined by liver-related death, liver transplantation, and complications of cirrhosis. We analyzed the prospectively collected data of 187 patients with a median follow-up of 5.8 years (range, 1.3-14 years). The survival rates without adverse outcome at 5 years and 10 years were 86% and 63%. Under UDCA therapy, laboratory liver parameters experienced the most prominent improvement in the first 3 months (P < 0.0001) and then stayed relatively stable for the following months. The Paris, Barcelona, Toronto, and Ehime definitions, but not the Rotterdam definition, applied at 3, 6, and 12 months significantly discriminated the patients in terms of long-term outcome. Compared with biochemical responses evaluated after 1 year of UDCA therapy, biochemical responses at the third month demonstrated higher positive predictive value (PPV) but lower negative predictive value (NPV) and increased negative likelihood ratio (NLR) by all definitions; biochemical responses at the sixth month showed higher or the same PPV and NPV and lower NLR by all definitions. Conclusion: For the previously published criteria, biochemical responses at the sixth month can be used in place of those evaluated after 1 year of UDCA therapy. Our findings justify a more rapid identification of patients who need new therapeutic approaches. (HEPATOLOGY 2013)

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