ALT above the healthy limit

Above 33 U/L for men or 25 for women, the ACG says the level "should be assessed by physicians," and its stated reason is mortality: "Elevated ALT or AST above the upper limit of normal (ULN) in a population without identifiable risk factors is associated with increased liver-related mortality." The cohorts behind that sentence include a Korean study in which men with an ALT of 30 to 39 had a 9.5-fold relative risk of liver-related death compared with under 20, and US survey data in which an elevated ALT (over 30 in men, 19 in women) carried an 11.2-fold increase in liver-related mortality. Those are relative risks in populations, not your odds.

First, repeat it. ACG Recommendation 1: "Before initiation of evaluation of abnormal liver chemistries, one should repeat the lab panel and/or perform a clarifying test (e.g., GGT if serum alkaline phosphate is elevated) to confirm that the liver chemistry is actually abnormal." The guideline gives no wait time after exercise, and none of the four documents behind this page does. What it does say is that strenuous exercise, muscle injury, thyroid disease and hemolysis can raise transaminases without liver disease, that muscle causes show up mainly as AST, and that a creatine kinase test is the screen for them.

How far above matters. The ACG grades elevations as multiples of the upper limit printed by the reporting laboratory, not of 33 or 25: borderline under 2 times, mild 2 to 5 times, moderate 5 to 15 times, severe over 15 times. Everything under 5 times gets the same first-line evaluation (Recommendation 16): history including alcohol, prescription, over-the-counter and herbal products; hepatitis B and C serology; iron studies with transferrin saturation and ferritin; and, for a person with an elevated BMI, diabetes, high lipids or high blood pressure, an ultrasound for fatty liver (Recommendation 5). If that is negative, the ACG's algorithm allows 3 to 6 months of observation with a repeat panel for a borderline value, 3 months for a mild one, before the second-line tests: autoimmune antibodies, ceruloplasmin for Wilson disease (especially under 55), alpha-1 antitrypsin phenotype, and celiac, thyroid and muscle screens. Moderate, severe and massive elevations "require immediate evaluation," and acute hepatitis with a prolonged prothrombin time or confusion "requires immediate referral to liver specialist."

The common cause and the score that follows it. The ACG says fatty liver "should be strongly considered in individuals with mild elevations of AST/ALT levels"; the AGA puts its prevalence at about 37 percent of US adults and 70 percent of people with type 2 diabetes. Both the AGA and AASLD stage it with FIB-4: under 1.3 (under 2.0 past 65) is low risk, 1.3 to 2.67 goes to elastography, over 2.67 is referred. The AASLD's referral rule for the enzyme itself is time: consider direct referral when aminotransferases are "persistently (> 6 mo) above normal," and it says an ALT chronically above 30 for 6 to 12 months may suggest "chronic liver injury."

What lowers it. For fatty liver the AASLD reports that "Weight loss of 3%–5% improves steatosis, but greater weight loss (> 10%) is generally required to improve NASH and fibrosis," and that "ALT normalization can predict NASH resolution." The AGA notes that 2 to 3 sessions of aerobic exercise a week lower aminotransferases "even in the absence of significant weight loss." The AASLD classifies alcohol as mild up to 20 g a day for women and 30 for men, says moderate use increases the probability of advanced fibrosis, and asks anyone with significant fibrosis to abstain completely; the ACG counsels cessation for women over 140 g and men over 210 g a week with an AST above ALT. Coffee at 3 or more cups a day "could be recommended," the AASLD says, on epidemiological evidence only.