Predictive Value of Assessing Peripheral Blood Mononuclear Cells Prior to Living Donor Liver Transpl

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Predictive Value of Assessing Peripheral Blood
Mononuclear Cells Prior to Living Donor Liver
Transplantation for Acute Rejection in HCV
Patients

• Y Li, T Koshiba, X Zhao, A Ito, H Kawamoto, Y
  Tanaka, A Koizumi, S Sakaguchi, N
  Minato, and K Tanaka
• Department of Transplantation and Immunology
• Kyoto University, Faculty of medicine, Kyoto,
  Japan

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Background 1

• Anti-rejection therapy after liver
  transplantation, especially steroid, facilitates
  HCV recurrence (Sheiner 1995)
• INF based anti-viral therapy could trigger
  rejection in HCV patients (Dousset 1994)
• Overlapping histologic features of acute
  rejection and recurrent HCV may result in
  diagnostic ambiguity. (McTaggart, 2004)

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Background 2

• Persistent HCV infection strikingly affects
  frequency and function of several lymphocyte
  subsets in the blood and liver.
• Viral-specific CD4() and CD8() T-cell responses
  persistent (Rosen 2003 review)
• Impaired function of NK cells (Jinushi 2004 )
• Upregulation of regulatory T cells CD4CD25
  (Cabrera, 2004) and IL-10 producing CD8
  (Accapezzato, 2004)
• A certain subset of ?dT cells infiltration into
  the liver (Tseng 2001)
• Decrease of hepatic NKT lymphocytes in chronic
  HCV infection patients (Deignan 2002)

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Aim
Hypothesis
Certain cellular responses caused by HCV
infection could modify anti-graft response in HCV
patients.

• To examine whether pre-Ltx assessment of
  peripheral blood mononuclear cell (PBMC) subsets
  predict early acute rejection (EAR) in HCV
  patients ( vs non-HCV patients)

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Material and Method
Patients

• Non-HCV
• N26 (f/m10/16)
• Age 41?15 y
• Primary Disease
• HBV with or without HCC 7/9
• PBC5
• BA 5
• PSC2 and etc
• ABO compatible or Identical

• HCV
• N22 (f/m6/16)
• Age 54?8 y
• Primary Disease
• HCV 4
• HCV with HCC 18
• ABO compatible or Identical

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Rejection

• Acute celluar rejection (ACR)
• biopsy-proven and graded according to Banff
  criteria
• Early acute rejection (EAR)
• defined as ACR diagnosed within 3 months
  post-Ltx

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FACS analysis
CD4 CD8
IL-2Rachain (CD25)
aßTcells(TCRaß) ?dTcells(TCR?d)
T cells (CD3)

NKTcells(CD3Va24Vß11)
B cells(CD19)
NKcells(CD3-CD56)
(Y Li et al Am J Transplant 2004)
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Statistical Analyses

• Student t test and Mann-Whitney U test
• To analyze difference between HCV and
  non-HCV groups or between rejection and
  non-rejection groups
• Kaplan-Meier analysis
• To analyze Free from ACR rate post-Ltx, and
  compared by use of the log rank test.
• Cox Proportional Hazard Model
• To detect risk factors for EAR

Plt0.05 significant
Plt0.05 significant
Plt0.07 significant
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Results
Patients Characteristics
Table 2
Table 1
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Cox proportion hazard Analysis
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Conclusion

• Immunological risk factors for EAR differ between
  HCV and non-HCV groups.
• This suggests that HCV infection itself causes
  immune changes which in turn alters
  susceptibility of rejection.
• Pre-Ltx knowledge of the risk of rejection may
  help to optimize especially post-Ltx outcome of
  HCV patients by tailoring anti-rejection and
  antiviral therapy