Donor organ shortage is the main limitation to liver transplantation as a treatment for end-stage liver disease (ESLD) and acute liver failure (ALF). Liver regenerative medicine may in the future offer an alternative form of therapy for these diseases, be it through cell transplantation, bioartificial liver (BAL) devices, or bioengineered whole organ liver transplantation. All three strategies have shown promising results in the past decade. However, before they are incorporated into widespread clinical practice, the ideal cell type for each treatment modality must be found, and an adequate amount of metabolically active, functional cells must be able to be produced. Research is ongoing in hepatocyte expansion techniques, use of xenogeneic cells, and differentiation of stem cell-derived hepatocyte-like cells (HLCs). HLCs are a few steps away from clinical application, but may be very useful in individualized drug development and toxicity testing, as well as disease modeling. Finally, safety concerns including tumorigenicity and xenozoonosis must also be addressed before cell transplantation, BAL devices, and bioengineered livers occupy their clinical niche. This review aims to highlight the most recent advances and provide an updated view of the current state of affairs in the field of liver regenerative medicine.

Introduction Identification of hospitalized patients with suddenly unfavorable clinical course remains challenging. Models using objective data elements from the electronic health record may miss important sources of information available to nurses. Methods We recorded nurses’ perception of patient potential for deterioration in 2 medical and 2 surgical adult hospital units using a 5-point score at the start of the shift (the Worry Factor [WF]), and any time a change or an increase was noted by the nurse. Cases were evaluated by three reviewers. Intensive care unit (ICU) transfers were also tracked. Results 31 159 patient-shifts were recorded for 3185 unique patients during 3551 hospitalizations, with 169 total outcome events. Out of 492 potential deterioration events identified, 380 (77%) were confirmed by reviewers as true deterioration events. Likelihood ratios for ICU transfer were 17.8 (15.2–20.9) in the 24 hours following a WF > 2, and 40.4 (27.1–60.1) following a WF > 3. Accuracy rates were significantly higher in nurses with over a year of experience (68% vs 79%, P = 0.04). The area under the receiver operator characteristic curve (AUROC) was 0.92 for the prediction of ICU transfer within 24 hours. Discussion This is a higher accuracy than most published early warning scores. Conclusion Nurses’ pattern recognition and sense of worry can provide important information for the detection of acute physiological deterioration and should be included in the electronic medical record.

The SRBAL improved survival, reduced ammonia, and accelerated liver regeneration in post-hepatectomy ALF. Improved survival was associated with a neuroprotective benefit of SRBAL therapy. These favorable results warrant further clinical testing of the SRBAL. This article is protected by copyright. All rights reserved.

Cell therapy is an emerging form of treatment for several liver diseases, but is limited by the availability of donor livers. Stem cells hold promise as an alternative to the use of primary hepatocytes. We performed an exhaustive review of the literature, with a focus on the latest studies involving the use of stem cells for the treatment of liver disease. Stem cells can be harvested from a number of sources, or can be generated from somatic cells to create induced pluripotent stem cells (iPSCs). Different cell lines have been used experimentally to support liver function and treat inherited metabolic disorders, acute liver failure, cirrhosis, liver cancer, and small-for-size liver transplantations. Cell-based therapeutics may involve gene therapy, cell transplantation, bioartificial liver devices, or bioengineered organs. Research in this field is still very active. Stem cell therapy may, in the future, be used as a bridge to either liver transplantation or endogenous liver regeneration, but efficient differentiation and production protocols must be developed and safety must be demonstrated before it can be applied to clinical practice.

Purpose of review To date, the only curative treatment for end-stage liver disease is liver transplantation, which is limited by the shortage of available organs. Cell therapy, in the form of cell transplantation or cell-based extracorporeal support devices, may in the future offer an alternative to transplantation, or at least provide liver function support as a bridging therapy until surgery may be performed. The purpose of this review is to highlight the most recent advances made in the field of cell therapy and regenerative medicine for the treatment of chronic liver disease (CLD). Recent findings After hepatocyte transplantation, long-term engraftment in the liver and spleen may be achieved, which can be stimulated through preconditioning, multiple infusions, and inflammatory response blockade. Mesenchymal stem cells are promising candidates for cell transplantation, as they have been shown to reduce liver fibrosis and support endogenous regeneration. Adipose tissue-derived stem cells are also being tested in this setting, due to their ready availability. Bioartificial liver (BAL) devices are being built that allow for effective preservation of hepatocytes, and one such device has recently demonstrated survival benefit in a porcine model of liver failure. Summary Cell transplantation of primary hepatocytes or stem cell-derived hepatocyte-like cells (HLCs) for the treatment of CLD holds promise. BAL systems may in the future be able to bridge acute-on-chronic liver failure patients to liver transplantation.