Liver Function Tests: What Subtle Patterns May Suggest

Liver function tests are among the most commonly requested blood tests, and mildly abnormal results are common, found in a substantial minority of adults in primary care. Many are dismissed as insignificant, some are over investigated, and a proportion represent genuine liver disease that benefits from early action. Reading liver tests well means understanding what each marker reflects, recognising patterns and working systematically through the causes.

What the tests measure

Enzyme levels indicate injury or cholestasis, not how well the liver is working. Albumin, INR and bilirubin better reflect function, and they are the markers that change in advanced liver disease.

Recognising the pattern

One practical tool is the ratio of ALT to ALP, each expressed as a multiple of its upper reference limit. A ratio above 5 suggests a hepatocellular pattern; below 2, a cholestatic pattern; between 2 and 5, a mixed pattern.

An AST to ALT ratio above 2 suggests alcohol related liver disease, while in fatty liver disease ALT is usually higher than AST until fibrosis develops. A rising AST to ALT ratio in someone with known fatty liver may signal advancing fibrosis.

What is normal?

Laboratory upper limits for ALT vary and are often derived from populations that include people with undiagnosed fatty liver disease. Some gastroenterology guidance has proposed lower upper limits for healthy ALT, around 33 units per litre in men and 25 in women. Conversely, ALT can be normal in people with significant fatty liver disease and fibrosis, which is why risk scores such as FIB 4 and elastography are used in people at metabolic risk.

Working through a mildly raised ALT

Guidance from gastroenterology societies recommends a systematic approach rather than simply repeating the test.

1. History: alcohol intake, medicines including over the counter and herbal products, supplements, bodybuilding products, travel, risk factors for viral hepatitis, family history of liver disease, recent intense exercise.
2. Metabolic assessment: weight, waist, glucose, lipids, blood pressure.
3. A liver aetiology screen as guided by the treating doctor: hepatitis B and C serology, iron studies for haemochromatosis, autoantibodies and immunoglobulins for autoimmune liver disease, coeliac serology, thyroid function, and in younger people tests for Wilson disease.
4. Imaging: ultrasound to look for steatosis, bile duct dilatation or other abnormalities.
5. Fibrosis assessment in suspected fatty liver disease using FIB 4 and elastography.

Coeliac disease deserves mention because it can cause raised transaminases that normalise on a gluten free diet. Muscle injury is another trap: intense exercise raises AST and sometimes ALT, and creatine kinase clarifies the source.

Herbal and supplement induced liver injury

Herbal and dietary supplements account for a growing share of drug induced liver injury in several countries. Products associated with liver injury include some bodybuilding supplements containing anabolic steroids, green tea extract, turmeric supplements, ashwagandha, kava, some traditional Chinese and Ayurvedic preparations and various multi ingredient products. Asking specifically about these, and checking resources such as LiverTox, is essential in any patient with unexplained liver test abnormalities.

Red flags

• ALT or AST more than about 10 times the upper limit
• Jaundice, dark urine, pale stools
• Raised INR or low albumin not otherwise explained
• Signs of chronic liver disease: ascites, confusion, bleeding
• Rapidly rising values
• Abnormal tests with weight loss, abdominal pain or a mass

Worked cases

The weightlifter

A 26 year old man has an AST of 110 and an ALT of 62 units per litre after a routine check. He trained heavily the day before and takes a bodybuilding supplement. Creatine kinase is markedly raised, suggesting muscle as the source. Repeat testing after a week without intense exercise shows normal AST and ALT. The supplement is reviewed for undeclared ingredients.

The wine drinker

A 54 year old woman has a GGT 3 times the upper limit, an AST of 70 and an ALT of 32, with a raised MCV. She drinks a bottle of wine most evenings. The pattern suggests alcohol related liver injury. Her doctor arranges fibrosis assessment and support to reduce drinking; her tests improve after 3 months of abstinence.

The unexpected diagnosis

A 31 year old woman with fatigue and a persistently raised ALT of 58 has a normal ultrasound and drinks little. Coeliac serology is positive and biopsy confirms coeliac disease. On a gluten free diet her ALT normalises.

The healing bone

A 70 year old woman has an isolated raised ALP with a normal GGT. Her vitamin D is very low and her PTH raised. The source is bone, from osteomalacia. Vitamin D replacement and calcium intake are addressed, and her ALP falls over months.

Beyond the enzymes

Liver test abnormalities are clues rather than diagnoses. Reading the pattern, asking about alcohol, medicines and supplements, considering metabolic and other causes and assessing fibrosis where appropriate allow practitioners to find the explanation and to identify the minority of patients whose livers need urgent attention.