In the last decades liver transplantation (LTx) has become a reliable life-saving procedure for patients with chronic end-stage liver diseases. LTx has an outstanding success rate in the first few years after allografting, especially considering that many patients are on the brink of survival at the time of transplantation. The success of LTx is owed to the pioneers who developed the surgical procedures and to researchers who discovered the medications to help prevent immunologic allograft rejection. However, several problems continue to impose serious limits on LTx today, including a shortage of donor livers, disease recurrence (e.g. hepatitis, hepatocellular cancer), preservation of long-term allograft function and anti-rejection drug side effects. While the organ shortage dilemma is not a focus of this review, we will address the latter issues as they relate to the "oldest" and "newest" approaches to immunosuppression, and discuss the prospect that recipients could potentially be made immunologically tolerant to liver transplants. Due to the critical organ shortage, new strategies to preserve transplanted liver allografts for the longest possible time are of paramount importance.
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