Efficacy and safety of liver support devices in acute and hyperacute liver failure: a systematic review and network meta-analysis

Acute liver failure (ALF) is a potentially life-threatening condition. Liver support therapies can be applied as a bridging-to-transplantation or bridging-to-recovery; however, results of clinical trials are controversial. Our aim was to compare liver support systems in acute and hyperacute liver failure with network meta-analysis. After systematic search, randomized controlled trials (RCT) comparing liver support therapies in adults with acute or hyperacute liver failure were included. In-hospital mortality was the primary outcome, the secondary outcomes were hepatic encephalopathy and mortality-by-aetiology. A Bayesian-method was used to perform network meta-analysis and calculate surface under the cumulative ranking curve (SUCRA) values to rank interventions. Eleven RCTs were included. BioLogic-DT and molecular adsorbent recirculating system (MARS) resulted in the lowest mortality (SUCRAs: 76% and 73%, respectively). In non-paracetamol-poisoned patients, BioLogic-DT, charcoal hemoperfusion and MARS may be equally efficient regarding mortality (SUCRAs: 53%, 52% and 52%, respectively). Considering hepatic encephalopathy, extracorporeal liver assist device (ELAD) may be the most effective option (SUCRA: 78%). However, in pairwise meta-analysis, there were no statistically significant differences between the interventions in the outcomes. In conclusion, MARS therapy seems to be the best available option in reducing mortality. Further research is needed on currently available and new therapeutic modalities. (CRD42020160133).

Pluripotent-Stem-Cell-Derived Hepatic Cells: Hepatocytes and Organoids for Liver Therapy and Regeneration

The liver is a very complex organ that ensures numerous functions; it is thus susceptible to multiple types of damage and dysfunction. Since 1983, orthotopic liver transplantation (OLT) has been considered the only medical solution available to patients when most of their liver function is lost. Unfortunately, the number of patients waiting for OLT is worryingly increasing, and extracorporeal liver support devices are not yet able to counteract the problem. In this review, the current and expected methodologies in liver regeneration are briefly analyzed. In particular, human pluripotent stem cells (hPSCs) as a source of hepatic cells for liver therapy and regeneration are discussed. Principles of hPSC differentiation into hepatocytes are explored, along with the current limitations that have led to the development of 3D culture systems and organoid production. Expected applications of these organoids are discussed with particular attention paid to bio artificial liver (BAL) devices and liver bio-fabrication.

Developing Activated Carbon From Date Seeds and Carbon Fiber for Use in Liver Support Devices

This work aims at utilizing natural resources and recycling materials from aircraft industries to enable their usage in medical and purification applications. The main application for which the materials are tested is the adsorption of bilirubin toxin from the liver of end stage liver failure patients. The two materials of concern are date seeds and carbon fiber reinforced polymers (CFRP). Samples of the materials will be treated to produce activated carbon (AC). Following the preparation of the ACs and chitosan coated ACs, tests are carried out to compare uncoated ACs with chitosan coated ACs. FTIR spectroscopy, TGA, DSC and a Spectrophotometer are utilized in order to characterize the samples obtained. From the data acquired, it is concluded that the chitosan coated ACs have better adsorption than the uncoated ACs. The activated carbon fibers showed the highest efficiency for the adsorption of bilirubin toxin. At an adsorbent dose of 0.8 gm, findings show that 98.4% of bilirubin toxin is adsorbed in samples where ACF is used as the adsorbent while 96.5% remained in samples where DPAC was used as the adsorbent.

Review of Extracorporeal Membrane Oxygenation and Dialysis-Based Liver Support Devices for the Use of Nephrologists

Acute kidney injury in the intensive care unit (ICU) is a manifestation of an underlying severe illness that commonly involves other organ systems. Pulmonary, cardiac, and hepatic failures are the most prevalent. This article provides a simplified review of the technical aspects of extracorporeal cardiopulmonary and liver support devices used in the adult ICU patient, as well as a summary of the most relevant and up-to-date clinical evidence that supports their use.

Extracorporeal liver support devices in the ICU

Liver failure is common and carries high morbidity and mortality. Liver transplantation (LT) is the only definitive treatment available performed as an emergency in acute liver failure and electively for chronic liver disease. In the last 50 years, a number of extracorporeal liver support devices and modifications have emerged , some of them purely mechanical in nature aimed at detoxification, while others are cell based systems possessing bio-transformational capability. Mechanical devices are mainly based on albumin dialysis, albumin being a key transporter protein that is severely deficient and irreversibly destroyed in liver diseases. Despite a sound scientific rationale and good safety profile, none of the currently available devices have shown enough promise to be incorporated in routine clinical practice, their use being limited to specific clinical situations. This chapter describes currently available devices, their operational characteristics, current evidence of their utility and limitation, and the future developments in the field of extracorporeal liver support.