Hepatic Tissue Engineering

Liver disease afflicts over 600 million people worldwide, 30 million of whom are Americans. Liver disease leads to the death of over 40,000 individuals in the United States every year. Liver failure can be generally separated into two major categories: fulminant hepatic failure, also referred to as acute liver failure, and chronic hepatic failure resulting from chronic end-stage liver disorders. The term fulminant hepatic failure is utilized for cases in which hepatic encephalopathy and impaired synthetic function (i.e., coagulopathy) develops within 26 weeks of the initial onset of jaundice. Hepatic encephalopathy is a neuropsychiatric condition, which can be divided into four stages ranging from minor effects such as mild confusion and sleep disorder, to deep coma. Although fulminant hepatic failure is relatively rare, with approximately 2,000 cases in the United States per year, it exhibits a high mortality rate of approximately 28% [1]. The major identified causes of fulminant hepatic failure include acetaminophen overdose, idiosyncratic drug reactions, and viral hepatitis A and B [1]. Of note, a recent multicenter etiology study showed that 17% of fulminant hepatic failure cases remained of indeterminate origin [2]. In addition to hepatic encephalopathy, other clinical manifestations of fulminant hepatic failure include bacterial and fungal infection, coagulopathy, as well as metabolic, cardiorespiratory, and hemodynamic abnormalities. Though spontaneous recovery has been observed due to the regenerative capacity of the liver, this type of recovery is difficult to predict, and rarely occurs in various etiologies, such as idiosyncratic drug toxicity and hepatitis B [1]. Liver transplantation is currently the only therapy shown to directly alter mortality, and therefore, is the standard of care in most clinical settings. As a result, all fulminant hepatic failure patients that meet the criteria for orthotopic liver transplant are immediately listed as United Network for Organ Sharing Status 1 (highest priority) upon presentation. Factors that preclude this designation are irreversible brain damage, unresponsive cerebral edema, uncontrollable sepsis, malignancy, and multisystem organ failure. Despite the effectiveness of liver transplant in improving short-term survival of fulminant hepatic failure patients, the utility of this approach remains limited due to the scarcity of donor organs.