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Fibrosis progression in human immunodeficiency virus/hepatitis C virus coinfected adults: Prospective analysis of 435 liver biopsy pairs

Authors

  • Monica A. Konerman,

    Corresponding author
    1. Johns Hopkins Hospital/University School of Medicine, Baltimore, MD
    • Address reprint requests to: Monica A. Konerman, M.D., University of Michigan Health System, Division of Gastroenterology, 3912 Taubman Center, 1500 East Medical Center Dr,, SPC 5362, Ann Arbor, MI 48109. E-mail: konerman@med.umich.edu; fax: 734-763-7834. or Mark S. Sulkowski, M.D., Johns Hopkins University School of Medicine, 600 North Wolfe St., 1830 Bldg., Ste. 445, Baltimore, MD 21287. E-mail: msulkowski@jhmi.edu; fax: 410-616-2831.

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  • Shruti H. Mehta,

    1. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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  • Catherine G. Sutcliffe,

    1. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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  • Trang Vu,

    1. Johns Hopkins Hospital/University School of Medicine, Baltimore, MD
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  • Yvonne Higgins,

    1. Johns Hopkins Hospital/University School of Medicine, Baltimore, MD
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  • Michael S. Torbenson,

    1. Johns Hopkins Hospital Department of Pathology, Baltimore, MD
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  • Richard D. Moore,

    1. Johns Hopkins Hospital/University School of Medicine, Baltimore, MD
    2. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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  • David L. Thomas,

    1. Johns Hopkins Hospital/University School of Medicine, Baltimore, MD
    2. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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  • Mark S. Sulkowski

    Corresponding author
    1. Johns Hopkins Hospital/University School of Medicine, Baltimore, MD
    • Address reprint requests to: Monica A. Konerman, M.D., University of Michigan Health System, Division of Gastroenterology, 3912 Taubman Center, 1500 East Medical Center Dr,, SPC 5362, Ann Arbor, MI 48109. E-mail: konerman@med.umich.edu; fax: 734-763-7834. or Mark S. Sulkowski, M.D., Johns Hopkins University School of Medicine, 600 North Wolfe St., 1830 Bldg., Ste. 445, Baltimore, MD 21287. E-mail: msulkowski@jhmi.edu; fax: 410-616-2831.

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  • Potential conflict of interest: Dr. Thomas consults for and received grants from Gilead and Merck. He consults for Janssen. Dr. Sulkowski advises and received grants from Gilead, AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Vertex, and Janssen.

  • Supported by grants K24DA00432, DA-11602, DA-16065, and DA-13806 from the National Institute on Drug Abuse, AA016893 from the National Institute on Alcohol Abuse and Alcoholism, K23 AT002862 (TTB) from the National Center for Complementary and Alternative Medicine, grant HS 07-809 from the Agency for Healthcare Policy and Research and the Clinical Research Unit at the Johns Hopkins Medical Institutions, M01RR-02719. This publication was made possible by grant number UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

Abstract

Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection is associated with progressive liver disease. However, the rate of progression is variable and the ability to differentiate patients with stable versus progressive HCV disease is limited. The objective of this study was to assess the incidence of and risk factors for fibrosis progression in a prospective cohort of coinfected patients. Overall, 435 liver biopsy pairs from 282 patients without cirrhosis were analyzed. Biopsies were scored according to the METAVIR system by a single pathologist blind to biopsy sequence. Fibrosis progression was defined as an increase of at least one METAVIR fibrosis stage between paired biopsies. The majority of patients were African American (84.8%), male (67.7%), and infected with HCV genotype 1 (93.4%). On initial biopsy, no or minimal fibrosis was identified in 243 patients (86%). The median interval between biopsies was 2.5 years. Fibrosis progression was observed in 97 of 282 (34%) patients and 149 of 435 (34%) biopsy pairs. After adjustment, greater body mass index (adjusted odds ratio [aOR]: 1.04 per 1 unit increase), diabetes (aOR: 1.56), and hepatic steatosis (aOR: 1.78) at the time of initial biopsy were marginally associated with subsequent fibrosis progression. Between biopsies, elevated serum aspartate and alanine aminotransferase (AST, ALT) (aOR AST: 3.34, ALT: 2.18 for >25% values >100 U/L versus <25% values >100 U/L) were strongly associated with fibrosis progression. Conclusion: Fibrosis progression is common among HIV/HCV coinfected patients; these data suggest that progression can be rapid. Persistent elevations in serum transaminase levels may serve as important noninvasive markers to identify subsets of patients who are more likely to progress and thus warrant closer monitoring and consideration of HCV treatment. (Hepatology 2014;59:767–775)

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