Combined Bio-histological assessment as a tool to refine diagnosis and avoid overtreatment of early T cell-mediated rejection after liver transplantation.

BACKGROUND

Early post-transplant T cell-mediated rejection (TCMR) is commonly defined by histology alone. However, isolated early histological rejection after liver transplantation (LT) often resolves spontaneously and may lead to overtreatment, excessive steroid exposure, and avoidable immunosuppression-related morbidity. Clinically meaningful criteria to distinguish patients who truly require treatment remain poorly defined.

METHODS

This single-center study included 421 consecutive adult LT recipients undergoing routine day-7 protocol biopsy between 2000 and 2016, managed with a standardized immunosuppression-minimization strategy and complete long-term follow-up. The Seven-Up score integrated day-7 Banff histology (0-9) with a biological score (Bio-score, 0-4) derived from dynamic changes in total bilirubin, platelet count, and eosinophil count between postoperative day 5 and day 7. Very early (< 15 d) clinically relevant rejection was defined as Banff 6-9 combined with Bio-score > 2. Incidence of histological and clinically relevant TCMR, graft survival, patient survival, and diagnostic performance of the Bio-score were analyzed.

RESULTS

At day 7, 157 recipients (37.3%) exhibited Banff 6-9 rejection, whereas 264 (62.7%) had Banff 0-5. A biopsy-only strategy would have resulted in steroid treatment in all 157 patients. Application of the Seven-Up score identified only 19 patients (4.5%) requiring very early antirejection therapy, sparing one in three recipients (138 patients, 32.8%). Long-term graft and patient survival were comparable between the treated and untreated groups. The Bio-score demonstrated good diagnostic accuracy for very early clinically relevant TCMR [area under the curve (AUC) = 0.78; 95% confidence interval (CI): 0.68-0.89; P < 0.001), supporting its role as a non-invasive surrogate of early immune activity.

CONCLUSIONS

In liver recipients managed with minimized immunosuppression, most early histological TCMR resolved without treatment. Combining histological and biological criteria substantially reduced overtreatment without compromising graft or patient survival. The Seven-Up score provides a pragmatic framework for personalized early post-transplant management and may inform clinical decision-making, endpoint definition, and future trial design. The bio-component of the score may serve as a tool to avoid risky biopsy in partial LT.