Most countries exclude human immunodeficiency virus (HIV)-positive patients from organ donation because of concerns regarding donor-derived HIV transmission. The Swiss Federal Act on Transplantation has allowed organ transplantation between HIV-positive donors and recipients since 2007. We report the successful liver transplantation from an HIV-positive donor to an HIV-positive recipient. Both donor and recipient had been treated for many years with antiretroviral therapy and harbored multidrug-resistant viruses. Five months after transplantation, HIV viremia remains undetectable. This observation supports the inclusion of appropriate HIV-positive donors for transplants specifically allocated to HIV-positive recipients.

The liver exhibits intrinsic immune tolerogenic properties that contribute to a unique propensity toward spontaneous acceptance when transplanted, both in animal models and in humans. Thus, in contrast to what happens after transplantation of other solid organs, several years following liver transplantation a significant subset of patients are capable of maintaining normal allograft function with histological integrity in the absence of immunosuppressive drug treatment. Significant efforts have been put into identifying sensitive and specific biomarkers of tolerance in order to stratify liver transplant recipients according to their need for immunosuppressive medication and their likelihood of being able to completely discontinue it. These biomarkers are currently being validated in prospective clinical trials of immunosuppression withdrawal both in Europe and in the United States. These studies have the potential to transform the clinical management of liver transplant recipients by mitigating, at least in part, the burden of lifelong immunosuppression.

Indefinite allograft acceptance after immunosuppression withdrawal (ISW), also known as operational tolerance (OT), can occur spontaneously after liver transplantation (LT) but reliable and reproducible prognosis of OT versus non‐OT outcomes remains elusive. To prime this, systematic extraction of OT‐predictive factors from the literature is crucial. We provide the first comprehensive identification and synthesis of clinical parameters and biomarkers predicting spontaneous OT in non‐autoimmune/non‐replicative viral LT recipients selected for ISW. We searched Embase, Medline, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform for articles, conference abstracts, and ongoing trials. We contacted principal investigators of stand‐alone abstracts and ongoing trials for unpublished data and screened citations and references of eligible articles. 23 articles reporting on 11 completed ISW studies, 13 abstracts, and five trial registry entries were included. Longer time between LT and ISW was the only clinical parameter that may increase the incidence of OT. Prognostic biomarkers conspicuously differed between pediatric and adult ISW candidates. These included allograft gene expression patterns and peripheral blood immune exhaustion markers for adults, and histological allograft scores for children. Our results will foster cross‐validation efforts to facilitate safe and harmonized candidate selection for successful ISW.