Management of Acute Liver Failure

Fulminant hepatic failure, a life threatening condition induced by massive hepatocellular necrosis may be associated with significant morbidity and mortality. A better understanding of the pathophysiology of this condition, associated with advances in intensive care management and liver transplantation have improved outcomes. This review describes recent advances in the management of fulminant hepatic failure as well as emerging therapies. INTRODUCTION Liver failure, induced by massive hepatocellular necrosis effects greater than 4,000 patients in the United States per year. Prior to the advent of liver transplantation and improvements in the intensive care unit management of afflicted patients, prognosis following liver failure had historically been poor. This review describes advances in ICU management as well as emerging therapies for patients with liver failure. DEFINITION The most widely accepted definition of liver failure as proposed by Trey and Davidson in 1970 (1)(2) described the onset of hepatic encephalopathy within 8 weeks following massive liver injury. Although purists recognize that the original description of fulminant liver failure typified patients without pre-existing liver disease, this review will encompass liver failure in patients with and without a previous history of chronic liver injury. ETIOLOGY The disease processes that induce liver failure (LF) can be divided into several broad categories; viral infection, metabolic and toxic hepatitis, and ischemia or hypoxia (Table 1). In addition, there are several conditions associated with preexisting liver disease that may be associated with a fulminant course. (Table 2) Several of the mechanisms that induce LF deserve further comment. VIRAL HEPATITIS Worldwide, viral hepatitis is the most common precipitant of acute LF (3). Although rare, Hepatitis A (HAV) may be associated with LF, especially in patients over age 40 (4) or in patients with pre-existing liver disease (5). Recent reports describe a significant incidence of LF following acute HAV infection in patients with chronic hepatitis C (6) . Both “wild type” and mutant Hepatitis B Virus (HBV) may induce LF (7), as well as in circumstances when HBV infection is associated with Delta Hepatitis (HDV) co-infection.(8). Although advances in molecular biologic techniques have enhanced the ability to diagnose viral hepatitis not caused by HAV or HBV hepatitis, the specific contribution of these viruses towards inducing LF remains uncertain. Clearly, Hepatitis E virus (HEV), especially in pregnant