AST Higher Than ALT: What It Can Mean (the De Ritis Ratio)

The De Ritis ratio is simply AST divided by ALT, both values in the same units (usually U/L). Example: AST 80 U/L and ALT 35 U/L give a ratio of about 2.3. On the other hand, AST 28 U/L and ALT 18 U/L also gives a ratio of about 1.6, even though both results are within the normal range — and in that situation a reversed ratio has no clinical meaning, because both enzymes are within reference limits. In many healthy people, especially women and older people, AST is slightly higher than ALT without any disease.

The ratio is useful only when at least one of the enzymes is clearly elevated. According to the ACG (American College of Gastroenterology) guideline, truly 'healthy' ALT values are around 29–33 U/L in men and 19–25 U/L in women — above those levels it is reasonable to evaluate the result, even if it lies within the laboratory's wider reference range. AST and ALT ranges differ between laboratories, methods and sexes, so always refer to the values on your own report.

The historical significance of the ratio goes back to observations from the 1980s and 1990s: in alcohol-related liver disease the ratio is typically above 2, and in chronic viral hepatitis and non-alcoholic steatosis usually below 1. Over time it turned out that the situation is more complex: the ratio also rises with the stage of fibrosis, regardless of cause. The studies below show both relationships.

In alcohol-related liver disease AST is usually raised noticeably more than ALT. There are several reasons and not all are fully explained. Alcohol damages the mitochondria of hepatocytes, and AST also exists in a mitochondrial form that is released into the blood with such damage. In addition, chronic heavy drinking is associated with a deficiency of the active form of vitamin B6 (pyridoxal phosphate), a cofactor for both aminotransferases, and ALT synthesis is more dependent on it than AST — one of the hypotheses explaining why ALT stays relatively low. The result is an AST/ALT ratio that often exceeds 2.

Two things are worth remembering from this study. First, the ratio does distinguish alcohol from metabolic steatosis at group level, but for an individual patient it is only a clue: the range of values was wide (from 0.3 to 2.8 in NASH patients and from 1.1 to 11.2 in those with alcohol-related disease), so there is clear overlap. Second, the rise of the ratio in NASH with fibrosis shows that an AST/ALT above 1 does not have to mean alcohol — it may mean the liver disease is already advanced.

In cirrhosis ALT activity often falls relative to AST, because fewer hepatocytes are active and the clearance of AST from the blood by the liver sinusoidal cells is impaired. An AST/ALT ratio above 1 in a liver disease unrelated to alcohol therefore raises suspicion of advanced fibrosis or cirrhosis. The classic 1988 study by Williams and Hoofnagle analysed the ratio in 177 patients with non-alcoholic chronic liver diseases: in most cases of viral hepatitis the ratio was below 1, but it correlated significantly with the presence of cirrhosis — in 100 patients with chronic hepatitis B the mean was 0.59 without cirrhosis and 1.02 with cirrhosis, and when cirrhosis first became manifest the ratio often exceeded 1.0.

Because AST is present outside the liver, its isolated rise with a normal ALT suggests a non-liver source. The most common is muscle tissue: intense exercise (especially with a large eccentric component), injuries, intramuscular injections, statins, and less often muscle diseases and hypothyroidism can raise AST without any liver involvement. The AST rise after a hard workout can last several days and may be larger than the rise in ALT — we discuss the details in our article on leg training and AST and ALT and in our entry on creatine kinase (CK), whose level helps to distinguish a muscle source from a liver one.

Other non-liver causes include myocardial infarction and other heart injuries (AST is used far less often than troponins to diagnose them), haemolysis and red cell diseases, kidney disease and hypothyroidism. A separate, very practical thread is in vitro haemolysis, i.e. the breakdown of red cells in the tube: incorrect collection, keeping the sample too long or shaking it too vigorously can inflate AST (red cells contain considerable amounts of this enzyme) without any disease in the patient. Many laboratories print a haemolysis index on the report — it is worth a glance.

If AST has been raised for months or years while ALT, GGT, CK, bilirubin and the liver picture are normal, one possible explanation is macro-AST. In this phenomenon the AST enzyme binds to immunoglobulins in the blood, forming a large complex (a macroenzyme) that is cleared from the circulation slowly. As a result serum AST activity is persistently raised although no organ disease is responsible. In a 2022 case report (Reddy et al.), macro-AST was described as an uncommon and benign cause of persistent isolated AST elevation, confirmed in a healthy adult man by polyethylene glycol (PEG) precipitation.

In a literature survey in which Rubin et al. (2017) compiled 51 reported measurements, macro-AST concentrations had a bimodal distribution: about 60% of values below 200 U/L and about 40% above 200 U/L, which fits well with the prolonged half-life of the complex compared with ordinary AST. The authors noted a limitation: the data came mostly from reports of patients with comorbidities. For the reader the conclusion is that macro-AST is a diagnosis of exclusion, to be considered only after typical causes have been excluded, and a definite diagnosis needs a test that is not routinely available in every laboratory.

The FIB-4 index is calculated from age, AST, ALT and platelet count — so the AST-to-ALT ratio itself is just one of its elements, not a stand-alone index. In a separate article we explain how to calculate it and how to interpret the result in the context of non-alcoholic fatty liver disease. We cover elastography (FibroScan) itself in our knowledge-base entry.

The NASH-versus-alcohol study mentioned above illustrates this well: the ranges of ratios in the two groups overlapped, and in non-alcoholic steatosis with cirrhosis the ratio averaged 1.4. If one relied solely on a value above 1, some people with advanced metabolic disease would be wrongly classed as drinkers — which has real consequences for the relationship with the doctor.

The De Ritis ratio is one of those tools that for decades sufficed for quick orientation and are today better treated as a first clue than a final result. When AST is higher than ALT, do not assume the worst or the best scenario at once. Start by checking that the result is really elevated and the sample was collected properly, then take training, drugs and alcohol into account, and only then ask for further work-up — CK, a full liver panel, a blood count with platelets and, where indicated, an assessment of fibrosis. This order spares both needless worry and oversights.