Elevated Liver Enzyme in Obesity Is Not Necessarily Fatty Liver Disease

Posted Oct 27, 2008.By Damian McNamara

ORLANDO (EGMN) - Consider a diagnosis other than nonalcoholic fatty liver disease when an obese child or adolescent presents with elevated levels of the liver enzyme alanine aminotransferase, a retrospective study suggests.

Other important diagnoses were missed - in some cases for years - when obesity was automatically assumed to be the culprit and no further clinical investigations were performed.

"It used to be that it goes without saying that it's fatty liver disease" when an obese pediatric patient presents with elevated serum levels of alanine aminotransferase (ALT), Dr. Daniel Preud'Homme said. But his experience was suggesting that this was not necessarily the case.

To find out more, Dr. Preud'Homme and his colleagues reviewed the medical records of 372 children and adolescents who were referred for evaluation and management of obesity to the pediatric healthy life center at the University of South Alabama in Mobile. A complete metabolic profile for each patient included liver testing with serum ALT measurements.

Mean age was 14 years and mean body mass index was 39 kg/m².

Of the 113 patients who had an abnormally high ALT (defined as greater than a laboratory cutoff of 48 U/L), 8 patients (7%) were eventually diagnosed with a condition other than nonalcoholic fatty liver disease.

"Seven percent doesn't sound like a lot, but it is. If you assume they [all] have fatty liver disease, you could be sitting on another disease," said Dr. Preud'Homme, a pediatric gastroenterologist at the university.

The index case was a 13-year-old girl who had four abnormally high ALT assays over 2 years. The results were attributed to her obesity only, when in fact she had autoimmune hepatitis type 1. In addition, the patient was being treated with steroids "which could be a problem with autoimmune hepatitis," Dr. Preud'Homme said during a poster presentation at the annual meeting of the American College of Gastroenterology.

Two other patients with abnormally high ALT levels had smooth muscle antibody-positive and antinuclear antibody-positive assays consistent with autoimmune hepatitis type 1. This finding supports a need for a more comprehensive evaluation in any patient with elevated ALT levels, obese or not, Dr. Preud'Homme said. He recommended comprehensive testing for all liver diseases, performing an ultrasound, and, in some cases, taking biopsies. He also suggested repeating the serum ALT test.

Interestingly, the degree of obesity was not associated with a higher likelihood of another diagnosis. "In terms of [body mass index], it did not matter how big you were. It was not related to this," Dr. Preud'Homme said.

Two other patients had indeterminate biopsies. "It could be early, but they had abnormal ALT and liver enzymes," Dr. Preud'Homme said. He plans to closely follow these patients and repeat the biopsies.

Two others who were originally assumed to have fatty liver disease were diagnosed with alpha-1 antitrypsin deficiency.

Another "very interesting case" was a child diagnosed with Wilson's disease. Wilson's disease is a rare, inherited condition in which a patient cannot fully metabolize copper. As a result, copper accumulates over time in the liver, brain, kidney, cornea, and other tissues in the body. Liver disease is the most common presentation in children, and neurologic disease is most common among young adults.

"Our observations show that if we assume ALT is just elevated because [patients] are obese, we are likely to miss other diseases," Dr. Preud'Homme said. "The percentage is high enough to warrant not ignoring it."

Some laboratories use a lower serum ALT cutoff value of 40 U/L, which might be more beneficial, Dr. Preud'Homme said. If this had been the protocol at his institution's laboratory, the prevalence of diagnoses other than fatty liver disease would have increased from 7% to 42% in the study population.