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The natural history of acute histologic rejection without biochemical graft dysfunction in orthotopic liver transplantation: A systematic review

Protocol biopsy results in the first few weeks after liver transplantation sometimes display histologic features of acute cellular rejection (ACR), even in the absence of significant clinical or biochemical dysfunction. At present there is no clear consensus about the need to treat such cases with adjuvant immunosuppression. This systematic review describes, from the available evidence, the natural history of untreated histologic ACR in the absence of biochemical graft dysfunction. An electronic search of the Medline, Embase, and Cochrane Library databases was performed to select studies that reported protocol liver biopsies in the early posttransplant period from 1983 to 2000. Studies that identified patients with ACR on protocol biopsy who were not treated with adjuvant immunosuppression formed the basis of the study group. Data from individual studies were extracted using standardized pro forma and pooled for descriptive analysis. The search identified 3431 studies, of which 516 were cited in full. Of these, 15 studies met all of the inclusion criteria. These 15 studies reported on 1566 patients who had protocol biopsies performed in the early posttransplant period, of which 1048 (67%) had histologic evidence of ACR. Three hundred and thirty one (32%) patients with histologic ACR on protocol biopsy had no associated biochemical graft dysfunction. Without treatment, only 14% of these patients subsequently developed biochemical graft dysfunction requiring adjuvant immunosuppression. Steroid‐resistant rejection and chronic rejection both had a prevalence of 4% in patients with untreated histologic ACR and no biochemical graft dysfunction. Withholding adjuvant immunosuppression from patients with histologic ACR and no biochemical graft dysfunction seems to be safe, as long as graft function is carefully monitored. The rationale for performing protocol biopsies in the absence of biochemical graft dysfunction is questionable.