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Expert strategy identifies etiology in indeterminate acute liver failure cases

Researchers were able to establish an etiologic diagnosis among nearly 50% of patients with previously indeterminate etiology of acute liver failure using a systematic analysis strategy that included diagnostic algorithms and expert opinion.

“Indeterminate or unknown etiology of acute liver failure is established after a careful history and a series of diagnostic blood tests are still unable to identify a clear cause for the serious liver injury,” Daniel R. Ganger, MD, from the Northwestern University Feinberg School of Medicine in Chicago, told Healio Gastroenterology and Liver Disease. According to Ganger and colleagues, indeterminate ALF etiology can also often result from incomplete testing or competing diagnoses.

Ganger and colleagues formed a causality adjudication committee that consisted of site investigators and outside senior hepatologists. The committee reviewed the initial examination data of 292 patients with indeterminate ALF or acute liver injury etiology.

The committee determined a new specific etiologic diagnosis for 48.6% of the original cases. Acetaminophen overdose was the most common re-adjudicated etiology among 45 patients.

“In the U.S., acetaminophen overdose remains the most common cause of acute liver failure. Medications and alternative therapies are also common,” Ganger said. “Physicians need to be educated about the risk of medications and also the importance of rapid diagnosis and early referral to tertiary centers that have transplant options.”

The committee determined 32 of the new acetaminophen overdose etiologies using APAP-adduct protein testing. Eight of the other patients received their diagnosis based on history of acetaminophen intake, positive but not toxic adduct results, and compatible chemistries. The researchers noted that history of acetaminophen intake was often “intentionally hidden or unavailable primarily due to altered mentation.”

“Once the adduct test becomes available, emergency rooms may apply this technology for rapid diagnosis of occult acetaminophen overdose,” Ganger said. “We found that it helped uncover about 20% of indeterminate cases.”

Twenty-four cases received a new diagnosis of drug-induced liver injury. In many cases, review of patient history included medications that were subsequently identified as hepatotoxic.

“We stress the importance of using resources such as Livertox and available expert opinion,” Ganger said, regarding the livertox.gov website, which the researchers used to search for evidence of overlooked DILI etiologies.

The other new etiologic findings included 34 cases of autoimmune hepatitis, 12 cases of hypovolemic shock or ischemia, five cases of hepatitis B, and two cases of hepatitis A.

“We found that indeterminate etiology of acute liver failure is less common in the U.S. than previously thought at 5.5% of all cases,” Ganger said. “This is also one of the lowest rates of indeterminate etiology reported compared to other countries or regions of the world.”

Ganger and colleagues noted that while their systematic analysis was able to establish common etiologic diagnoses, the process remained challenging for senior clinicians. They recommend the use of a checklist to encourage more complete initial testing, such as the one developed by the Acute Liver Failure Study Group. – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.