SOUTH LAKE TAHOE, CALIF. — Attribute a mild chronic elevation in alanine aminotransferase to fatty liver disease only after considering eight other diagnoses, Dr. Christopher L. Bowlus advised at an update in gastroenterology and hepatology sponsored by the University of California, Davis.
He offered an algorithm for work-up of a patient whose serum alanine aminotransferase (ALT) is 1.5 times higher than the upper limit of normal, as defined by your clinical laboratory. If a physician doesn't do the work-up he described, a treatable condition will be missed in these patients 10% of the time, studies suggest.
The algorithm is based on consensus among physicians, because data on the subject are sparse, he added. “These are very common problems, but no one has really taken the time to look at what is the most effective or cost-effective way of evaluating patients,” said Dr. Bowlus of the university.
After ruling out four common causes of mild, chronic ALT elevation (alcoholic hepatitis, hepatitis B or C infection, and exposure to drugs or toxins that alter ALT), consider four less common diagnoses before fatty liver disease: hemochromatosis, autoimmune hepatitis, alpha-1 antitrypsin deficiency, and Wilson's disease.
When taking the patient's history, ask about alcohol use and parenteral exposures to viral infection through sexual activity, intravenous drug use, or blood transfusion prior to 1990. Inquire about illicit or prescribed drugs or herbal therapies, supplements, and over-the-counter medications that may affect ALT levels. The presence of diabetes is a risk factor for fatty liver disease.
Determine not only if the patient is an immigrant from a region with endemic hepatitis B but also if the patient's parents fit this description. “I've seen lots of positive hepatitis B students born in the United States” whose parents are immigrants, he said.
The physical exam will lead to a specific diagnosis in a minority of patients with ALT elevations. Look for signs of chronic liver disease, such as “spider” lesions on the skin (which can be subtle and usually are on the upper torso), palmar erythema, temporal wasting, hepatomegaly (common in alcoholic liver disease), and splenomegaly (often an early sign of portal hypertension). If the ALT elevation has been present for at least 6 months or the patient is symptomatic or has risk factors for hepatitis B or C infection, it's reasonable to order some lab tests. Get a hepatitis B surface antigen test and a hepatitis C antibody test; negative results rule out these viral infections. An ultrasound of the liver would be appropriate.
A transferrin saturation test is a good screening tool for hemochromatosis. If you need further testing for this condition, a genetic test is the way to go, but be prepared to explain potentially confusing results, Dr. Bowlus suggested.
If none of these leads to a diagnosis, order an antinuclear antibody test to screen for autoimmune hepatitis. A more specific screening tool is the anti-smooth muscle antibody level; a serum protein electrophoresis also can test for this disease.
Get a serum alpha-1 antitrypsin level to screen for alpha-1 antitrypsin deficiency. “We think of this as causing lung disease, but it can cause liver disease alone without lung disease,” he said.
A ceruloplasmin test is helpful to screen for Wilson's disease, an uncommon disease of copper metabolism that usually presents in childhood or early adulthood, although there have been case reports of diagnosis in people in their 50s and 60s.
If none of these potential diagnoses hits the mark, ask the patient to refrain from alcohol and any potentially offending medications or herbs and retest the ALT level in 3–6 months, he said. If ALT remains elevated, repeat all tests.
“If all this is negative, then you should consider that they might have fatty liver disease, particularly if the ultrasound is consistent with fatty liver disease and they have risk factors for fatty liver disease,” he said.
For many patients with elevated ALT who are diabetic or have high cholesterol, all these tests will be negative except that the ultrasound will show a fatty liver.
The appropriateness of a liver biopsy at this point is controversial.
'If all this is negative, then you should consider that they might have fatty liver disease.' DR. BOWLUS