New Recommendations Call for Standard ALT Screenings

From the American Association for the Study of Liver DiseasesAlarming Evidence Shows Elevated ALT Ups Mortality by 60%

BOSTON—Knowing your alanine aminotransferase (ALT) level, like knowing your blood pressure, fasting blood glucose, hemoglobin A1c, and cholesterol levels, should become part of basic personal health awareness, according to new recommendations from the American Association for the Study of Liver Diseases (AASLD) that were presented at the association’s annual meeting.

ALT, a protein made predominantly in the liver, participates in the modification of amino acids. Mounting evidence from population-based studies has documented a strong association between elevated ALT levels and subsequent mortality. Mortality rates jump by 60% to 80% when ALT goes beyond twice the upper limit of normal, with the risk further magnified among women.

Adrian M. Di Bisceglie, MD, chief of hepatology, Saint. Louis University School of Medicine, and chairman of public policy for the AASLD, said at the meeting that abnormal ALT activity is often ignored or minimized by physicians who construe them to be clinically insignificant in asymptomatic patients. “Every raised ALT is worthy of examination,” he stated, “especially when it persists over 3 to 6 months.”

The American Liver Foundation estimates that 30 million Americans, knowingly or not, have liver disease. With the epidemic rise in the prevalence of obesity and metabolic syndromes, the most common cause of ALT elevations in North America is fat accumulation within liver cells, known as non-alcoholic fatty liver disease (NAFLD). Fat accumulations in the liver are toxic. Other causes of ALT elevations include excessive alcohol consumption, chronic hepatitis virus infection, drug toxicity, and genetic and autoimmune liver diseases.

“Also of great concern is a new message emerging over the last 3 to 4 years that the mortality risk is raised with elevated ALT, not only in liver disease but also in non—liver-related ailments, particularly cardiovascular disease,” Dr Di Bisceglie said. “A persistently raised ALT is a symptom that one’s body is sick, usually because one is overweight or on the way to diabetes.”

Dr Di Bisceglie estimated that in any group of 100 patients with raised ALT levels, about:

• 30-40 would have NAFLD

• 10-20 would have hepatitis

• 5-10 would have alcohol-related increases

• 5 would have bile duct disorders

• 5 would have autoimmune liver diseases.

Finally, in about 15 to 20 patients, raised ALT would be related to drugs and medicines. The etiology is unknown in others.

Among the drugs most likely to cause acute liver injury, acetaminophen can be the most dangerous, because of its toxicity at relatively low doses, especially in those with high alcohol consumption. This drug and others with liver-harming potential (eg, anticonvulsants, antibiotics, and statins) account for 80% of drug-related liver toxicities.

What then is an elevated ALT level? The lack of standardization among laboratories, Dr Di Bisceglie conceded, is part of the problem. Different labs can define anywhere from 40 to 65 U/L as normal. “Unfortunately,” he said, “their samplings conducted to determine what is normal can include high proportions of overweight patients with a bit of fatty liver disease that push the normal range up. That’s why we need an effort to create a national standard.” A level of 60 U/L should be considered mildly ele-vated, he says.

The new recommendations call for making ALT a standard screening metric and requiring further investigation when abnormal levels are detected. “It is not a fancy test, but simply part of the standard multiphasic panels included with the blood test,” he noted.

The important point is that many liver diseases can be treated when they are caught early. “We don’t want physicians to ignore ALT elevations, because they very often are a flag for potentially serious liver disease,” Dr Di Bisceglie emphasized.