Bioartificial liver support for acute liver failure

Abstract

Acute liver failure (ALF) is a life-threatening condition characterized by rapid hepatic deterioration, coagulopathy, and encephalopathy. While orthotopic liver transplantation (OLT) is often necessary, donor organ shortages and the unpredictable course of ALF highlight the need for alternative supportive therapies. Bioartificial liver (BAL) systems offer a potential bridge to OLT or spontaneous liver recovery by providing metabolic and synthetic liver functions. Early extracorporeal liver support efforts relied on artificial-liver devices, which primarily performed detoxification but failed to improve survival. This led to the development of BAL systems incorporating viable hepatocytes to support both metabolic detoxification and biosynthetic functions. Initial BAL studies, including the HepatAssist® system, demonstrated improvements in biochemical parameters and hepatic encephalopathy, though survival benefits remained inconsistent. BAL devices comprise functional subunits, including filtration, detoxification, and bioreactor components housing hepatocytes. Various cell sources have been explored, including porcine hepatocytes, immortalized human cell lines, and induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells. While porcine hepatocytes remain widely used due to their metabolic activity, concerns regarding immunogenicity and zoonotic transmission persist. Clinical trials of BAL devices have shown biochemical and neurologic improvements but have yet to demonstrate definitive survival benefits. Recent advances, such as hepatocyte spheroid culture and iPSC-derived hepatocytes, may enhance BAL efficacy. Further research is needed to optimize cell sources, bioreactor designs, and integration with existing liver failure management strategies. While BAL systems offer a promising approach for ALF management, their clinical efficacy remains unproven. Continued advancements in cell technology and bioreactor design are necessary to establish BAL as a viable therapeutic option.