Acetaminophen-related acute liver failure in the United States

Abstract

Acetaminophen overdoses are the number one cause of acute liver failure (ALF) in the United States; they account for 50% of all cases of ALF and carry a 30% mortality. Nevertheless, acetaminophen is a highly successful product with sales easily exceeding a billion dollars annually. A narcotic-containing acetaminophen preparation is the number one generic drug sold in the United States. Historically, a strong association was claimed with alcohol as a co-factor and the accidental nature of ingestions was emphasized but the association with alcohol remains a matter of debate. Recently, a very reliable assay has been developed which detects a byproduct of the toxic reaction, acetaminophen-CYS adducts, protein-acetaminophen compounds that are released from damaged hepatocytes in similar fashion to aminotransferases. The US Acute Liver Failure Study Group is a multi-center network established to gather data prospectively on all forms of acute liver failure, a rare but often fatal condition. The group has data on more than 500 acetaminophen cases and described 275 of them in detail in a recent paper. The clinical pattern of presentation is somewhat different in the US compared with the UK, since nearly half are considered to be unintentional, the result of overuse of acetaminophen-containing compounds for pain relief, without suicidal intent. Despite the relatively good prognosis for acetaminophen overdoses, 30% die once acute liver failure occurs and this is the largest cause of death in the entire ALF registry.