BACKGROUNDOrthotopic liver transplantation (OLT) is the only treatment for end-stage liver failure; however, graft shortage impedes its applicability. Therefore, studies investigating alternative therapies are plenty. Nevertheless, no study has comprehensively analyzed these therapies from different perspectives.AIMTo summarize the current status of alternative transplantation therapies for OLT and to support future research.METHODSA systematic literature search was performed using PubMed, Cochrane Library and EMBASE for articles published between January 2010 and 2018, using the following MeSH terms: [(liver transplantation) AND cell] OR [(liver transplantation) AND differentiation] OR [(liver transplantation) AND organoid] OR [(liver transplantation) AND xenotransplantation]. Various types of studies describing therapies to replace OLT were retrieved for full-text evaluation. Among them, we selected articles including in vivo transplantation.RESULTSA total of 89 studies were selected. There are three principle forms of treatment for liver failure: Xeno-organ transplantation, scaffold-based transplantation, and cell transplantation. Xeno-organ transplantation was covered in 14 articles, scaffold-based transplantation was discussed in 22 articles, and cell transplantation was discussed in 53 articles. Various types of alternative therapies were discussed: Organ liver, 25 articles; adult hepatocytes, 31 articles; fetal hepatocytes, three articles; mesenchymal stem cells (MSCs), 25 articles; embryonic stem cells, one article; and induced pluripotent stem cells, three articles and other sources. Clinical applications were discussed in 12 studies: Cell transplantation using hepatocytes in four studies, five studies using umbilical cord-derived MSCs, three studies using bone marrow-derived MSCs, and two studies using hematopoietic stem cells.CONCLUSIONThe clinical applications are present only for cell transplantation. Scaffold-based transplantation is a comprehensive treatment combining organ and cell transplantations, which warrants future research to find relevant clinical applications.