Peritransplant absolute lymphocyte count as a predictive factor for advanced recurrence of hepatitis C after liver transplantation

Authors

  • Shunji Nagai,

    1. Division of Transplant and Hepatobiliary Surgery, Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
    Search for more papers by this author
  • Atsushi Yoshida,

    1. Division of Transplant and Hepatobiliary Surgery, Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
    Search for more papers by this author
  • Keisuke Kohno,

    1. Division of Transplant and Hepatobiliary Surgery, Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
    2. Department of Surgery, Division of Gastroenterological and Hepatobiliary Surgery and Organ Transplantation, University of Tsukuba, Tsukuba, Japan
    Search for more papers by this author
  • David Altshuler,

    1. Division of Transplant and Hepatobiliary Surgery, Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
    Search for more papers by this author
  • Mio Nakamura,

    1. Division of Transplant and Hepatobiliary Surgery, Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
    Search for more papers by this author
  • Kimberly A. Brown,

    1. Division of Gastroenterology, Henry Ford Hospital, Detroit, MI
    Search for more papers by this author
  • Marwan S. Abouljoud,

    1. Division of Transplant and Hepatobiliary Surgery, Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI
    Search for more papers by this author
  • Dilip Moonka

    Corresponding author
    1. Division of Gastroenterology, Henry Ford Hospital, Detroit, MI
    • Address reprint requests to: Dilip Moonka, M.D., Division of Gastroenterology, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202. E-mail: DMOONKA1@hfhs.org; fax: 313-916-5960.

    Search for more papers by this author

  • See Editorial on Page 21

    Potential conflict of interest: Dr. Brown advises and received grants from Vertex, Gilead, and Merck. She advises Janssen, Gilead, Genentech, Bayer Onyx, and Novartis, and received grants from Hyperion, Exelenz, Bristol-Myers Squibb, and Massbiologics. She consults for CDLF.

Abstract

Lymphocytes play an active role in natural immunity against hepatitis C virus (HCV). We hypothesized that a lower absolute lymphocyte count (ALC) may alter HCV outcome after liver transplantation (LT). The aim of this study was to investigate the impact of peritransplant ALC on HCV recurrence following LT. A total of 289 LT patients between 2005 and 2011 were evaluated. Peritransplant ALC (pre-LT, 2-week, and 1-month post-LT) and immunosuppression were analyzed along with recipient and donor factors in order to determine risk factors for HCV recurrence based on METAVIR fibrosis score. When stratifying patients according to pre- and post-LT ALC (<500/μL versus 500-1,000/μL versus >1,000/μL), lymphopenia was significantly associated with higher rates of HCV recurrence with fibrosis (F2-4). Multivariate Cox regression analysis showed posttransplant ALC at 1 month remained an independent predictive factor for recurrence (P = 0.02, hazard ratio [HR] = 2.47 for <500/μL). When peritransplant ALC was persistently low (<500/μL pre-LT, 2-week, and 1-month post-LT), patients were at significant risk of developing early advanced fibrosis secondary to HCV recurrence (F3-4 within 2 years) (P = 0.02, HR = 3.16). Furthermore, severe pretransplant lymphopenia (<500/μL) was an independent prognostic factor for overall survival (P = 0.01, HR = 3.01). The use of rabbit anti-thymocyte globulin induction (RATG) had a remarkable protective effect on HCV recurrence (P = 0.02, HR = 0.6) despite its potential to induce lymphopenia. Subgroup analysis indicated that negative effects of posttransplant lymphopenia at 1 month (<1,000/μL) were significant regardless of RATG use and the protective effects of RATG were independent of posttransplant lymphopenia. Conclusion: Peritransplant ALC is a novel and useful surrogate marker for prediction of HCV recurrence and patient survival. Immunosuppression protocols and peritransplant management should be scrutinized depending on peritransplant ALC. (Hepatology 2014;58:35–45)

Ancillary