The Acute Liver Failure Study Group (ALFSG) was a clinical research network that collected data and biospecimens from participants with acute liver failure (ALF) and acute liver injury (ALI). ALF is defined as a severe form of acute liver injury characterized by rapid onset over days and weeks in the absence of underlying cirrhosis, leading to abnormal coagulation with prolongation of the prothrombin time (INR ≥ 1.5) in the presence of altered mentation. ALI is defined as a severe acute liver injury with an INR ≥ 2.0 and no encephalopathy (altered mental functioning, drowsiness, or coma). Outcomes vary, but nearly 29% die while another 22% undergo liver transplantation, and the remaining recover fully in general. A unique feature of ALF and ALI is that there are a variety of causes, all of which share similar clinical features (coagulopathy, encephalopathy, susceptibility to infection, and bleeding) regardless of cause. The most frequent causes are acetaminophen overdose, drug-induced liver injury, autoimmune hepatitis, and viral hepatitis B, but less common causes include acute fatty liver of pregnancy, ischemia/shock, Wilson disease, heat stroke, and metastatic cancer.

ALFSG conducted a Multi-Center Trial to Study Adult Acute Liver Failure (AALF) with ALF and ALI participants and those less severe that had coagulopathy but not the threshold of encephalopathy, a pilot study with a subset of AALF participants using rotational thromboelastography as a dynamic measure of coagulation, and a clinical trial with a subset of AALF participants using 13C labeled methacetin breath testing to determine outcomes in ALF patients being considered for transplantation.

The primary objectives were to collect clinical and epidemiological data as well as biospecimens (serum, plasma, urine, tissue, DNA) from participants with ALF, ALI, or those with coagulopathy but did not reach the threshold of encephalopathy.

The primary outcome measure was overall survival of participants.

ALF inclusion criteria:

• Altered mentation of any degree (encephalopathy)
• Evidence of moderately severe coagulopathy (INR ≥ 1.5)
• A presumed acute illness onset of less than 26 weeks

• Cirrhosis patients
• Alcohol induced liver failure
• Known pre-existing chronic liver disease

• Acetaminophen (APAP) etiology: Acute illness < 2 weeks
• Non-acetaminophen etiology: Acute illness < 26 weeks
• INR ≥ 2.0, ALT ≥ 10X ULN, TBili ≥ 3 mg/dL

• Altered mentation of any degree (encephalopathy)

While the severity of illness did not decline over the course of the study, improvements in outcomes were observed. For example, the numbers requiring listing for transplantation, those receiving transplant, and those dying of ALF all declined during the study period. Participants with acetaminophen toxicity listed for transplantation were more severely ill and less likely to receive a liver transplant than those with any other etiology. Furthermore, participants with acetaminophen overdoses had an outcome by day 4 following admission, emphasizing how rapid deterioration can occur as well as recovery.