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Is there a role for extracorporeal liver support as a bridge to liver transplantation in acute liver failure?

Mortality in acute liver failure (ALF) is high, with liver transplantation offering the only chance of survival in the most severe cases (1). However, with the increasing shortage of donor organs, a treatment strategy to prolong survival during the wait for transplantation is required. Extracorporeal liver support (ELS) systems aim to support the failing liver, potentially facilitating regeneration or prolonging survival until a suitable organ donor can be found. Artificial systems center on albumin dialysis, removing protein-bound and soluble toxins. Bioartificial systems incorporate porcine hepatocytes or human hepatoblastoma cells aiming to combine detoxification and synthetic liver functions. Using ELS systems to provide a “bridge to transplantation” has been widely considered, but ELS use remains restricted to a minority of specialist centers. In a recent meta-analysis, results demonstrated survival benefit for ELS use in ALF but not in acute-on-chronic liver failure (2). However, randomized controlled trials have either been small ( 20 participants) or recruit patients from multiple centers (up to 20 centers), often with lengthy recruitment periods (3–11). With ELS devices representing a considerable investment and new devices under development, it is necessary to consider the current demand for an ELS device to prolong survival to transplantation in ALF at a single transplant center. This investigation examines experience at a regional transplant center (Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, United Kingdom) serving a population of approximately 6 million. A prospectively collated database for patients presenting with ALF, categorized as top priority for transplantation (super-urgent), between November 1992 and November 2009 was reviewed. One hundred forty-nine patients presenting with ALF were listed for superurgent liver transplantation. Etiology of ALF included paracetamol overdose (n 76), non-A-E hepatitis (n 39), idiosyncratic drug reaction (n 9), autoimmune hepatitis (n 8), hepatitis B (n 4), Budd-Chiari syndrome (n 4), Wilson’s disease (n 3), hepatitis A (n 1), and unknown etiology (n 5). One hundred twenty-four patients (83%) underwent liver transplantation, and the majority were performed by day 3 (Fig. 1). Twentyfour patients (16%) died of ALF before transplantation without sepsis. This equates to a mean of 1.5 eligible patients per year dying without receiving liver transplantation. One patient’s clinical condition improved without transplantation. These data demonstrate that although there is a role for prolonging survival to transplantation in ALF, the majority of patients do undergo liver transplantation promptly. Time to death was rapid, suggesting that an ELS therapy capable of short-term survival benefit could considerably improve the chance of patients receiving a liver transplant. Despite the apparent need for prolonged survival in these critically ill patients, these data suggest that only 1.5 patients per year with ALF categorized as superurgent could have benefited from a “bridge to transplantation.” In the United Kingdom, patients with the highest risk of death from ALF, based on modified Kings College criteria, are termed “super-urgent” (12). “Super-urgent” patients can receive the most suitable organ from the National pool. Similar waiting times have been reported by other countries where such allocation systems exist. A single-center Canadian series achieved a mean waiting time to transplantation of 2.7 days (1). A French series involving 16 centers reported that 90% underwent transplantation within 48hours (13). In the United States, a regional allocation pool is available, with 95% undergoing transplantation within 8 days (14). Direct comparisons between series are complicated by differences in definitions and data acquisition; however, they do demonstrate the prompt nature of liver transplantation for the sickest patients. In countries where donor pools are more limited, the proportion of patients with ALF dying before transplantation may be higher, potentially resulting in a greater role for ELS. Setting a time point beyond which ELS may be beneficial is currently without evidence base. It may be suggested in the absence of an urgent liver transplantation service or where the wait for transplantation may be lengthy, instituting ELS may offer the only hope of survival. The ideal situation is that ELS could negate the requirement for transplantation, supporting the liver during its recovery. Although there is some evidence that this may be possible, it is