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Abstract
Background
With advances in immunosuppression, graft and patient survival rates have increased significantly, but acute cellular rejection remains an important problem following liver transplantation (LT), and late acute rejection (LAR) occurs in a small percentage of recipients. Some risk factors for LAR have been identified, yet the cause of LAR has not been completely investigated. The efficacy of mycophenolate mofetil (MMF) administered in combination with calcineurin inhibitor (CNI) for reduction of LAR has been demonstrated.
Methods
Between January 2006 and August 2007, adult LT recipients (n=309) were enrolled in this study. Biopsy-proven acute rejection that occurred ＞6 months after LT was defined as LAR. The immunosuppression regimens, CNI or CNI plus MMF, were used continuously for at least 6 months after LT. The mean follow-up period was 34.8 months (range, 25∼46 months).
Results
LAR occurred in 17 cases (5.5%). The incidence of LAR in the CNI (n=138) or CNI plus MMF groups (n=171) was 8.6% (n=12) and 2.9% (n=5), respectively (P=0.015). Multivariate Cox regression confirmed that CNI plus MMF versus CNI therapy is associated with a decreased risk of LAR (relative risk, 0.33; P=0.04).
References
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Fig. 1.
Etiology of liver disease. (A) Patients without late acute rejection (LAR). (B) Patients with LAR. Abbreviations: HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LC, liver cirrhosis; PBC, primary biliary cirrhosis.
Fig. 2.
Kaplan-Meier analysis. (A) LAR-free survival rate between CNI and CNI＋ MMF group (log-rank test; P=0.042). (B) Overall survival rate between LAR and No LAR group (log-rank test; P=0.0023). Abbreviations: LAR, late acute rejection; CNI, calcineurin inhibitor; MMF, mycophenolate mofetil.
Table 1.
Target trough levels of calcineurin inhibitors of our center
| Postoperative time (months) | Tacrolimus (ng/mL) | Cyclosporine (ug/mL) |
|---|---|---|
| 1 | 15∼16 | 150∼180 |
| 6 | 9∼11 | 100∼120 |
| 12 | 6∼8 | 80∼100 |
Table 2.
Baseline clinical characteristics
Table 3.
Immunosuppression levels at the time of 1, 6, 12 months follow-ups after liver transplantation
Table 4.
Comparison of CNI trough level in No late acute rejection group
| Months | No LAR | P | ||
|---|---|---|---|---|
| CNI | CNI＋ MMF | |||
| FK (ng/mL) | 1 | 18.2 | 14.9 | 0.04 |
| (mean) | 6 | 9.3 | 7.9 | 0.02 |
| 12 | 7.6 | 7.1 | 0.65 | |
| CSA (ug/mL) | 1 | 143 | 186 | 0.36 |
| (mean) | 6 | 97 | 105 | 0.69 |
| 12 | 91 | 94 | 0.88 | |
Table 5.
Relative risk of LAR-free survival with Cox proportional hazard model (Univariate analyses of demographic characteristics)
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