All 10 liver tests: what each one shows and when to see a doctor

The main point

The liver rarely hurts, so we judge it by tests. The good news: a small set of simple tests gives a fairly complete picture. Ten tests answer four questions: are the cells intact, does bile flow freely, is the liver coping with its work, and are there hidden causes such as iron and viruses.

Cell injury: ALT and AST

ALT (alanine aminotransferase) is found mainly in the liver and leaks into the blood when cells are injured. Laboratories often print an upper limit of 40 U/L. In a study of 6,835 donors, limits were calculated from the subgroup at lowest risk of liver disease; healthy limits turned out lower: 30 U/L in men and 19 U/L in women (Prati D Ann Intern Med 2002. PMID 12093239^[1]). The AASLD 2023 guidance advises attention if ALT or AST is above 30 U/L intermittently or for 6–12 months in a row: this may point to chronic liver injury (Rinella M E Hepatology 2023. PMID 36727674^[2]). With a small rise, fatty liver is checked first.

AST (aspartate aminotransferase) is also found in muscle, heart and kidney, so a rise in AST without ALT more often points to muscle or heart, and a hard workout raises mainly AST (Kwo P Y Am J Gastroenterol 2017. PMID 27995906^[3]). An AST to ALT ratio of 2:1 or more is linked with alcohol-related injury, and above 3:1 it is more likely. A doctor asks about alcohol in anyone with abnormal values.

Bile flow: GGT, ALP, bilirubin

ALP (alkaline phosphatase) rises when bile outflow is obstructed, even slightly. It is also found in bone, placenta and intestine: in people over 50, especially women, the level is higher because of bone turnover. GGT (gamma-glutamyltransferase) helps establish where ALP comes from: if GGT is also up, the source is the liver. But GGT is non-specific and is not used as a stand-alone screen (Kwo P Y Am J Gastroenterol 2017. PMID 27995906^[3]).

Bilirubin forms when old red cells break down; the liver binds it and removes it in bile. Total bilirubin is usually below 19 µmol/L (1.1 mg/dL). The commonest cause of raised unconjugated bilirubin is Gilbert syndrome (a common, hereditary and harmless trait): total bilirubin is usually below 51 µmol/L (3 mg/dL) and almost never above 103 µmol/L (6 mg/dL); fasting or illness can raise it 2–3 times, and it falls after eating.

The liver as a factory: albumin and INR

Albumin is made only by the liver, stays in the blood for about 3 weeks, and a normal level is from 35 g/L (3.5 g/dL). A fall usually means liver disease lasting more than 3 weeks, but any serious illness can lower it. Prothrombin time and INR (international normalised ratio) react faster: they change within a day. They lengthen when clotting factors fall below 10% of normal; without liver disease the cause is more often vitamin K deficiency or blood-thinning medication (Kwo P Y Am J Gastroenterol 2017. PMID 27995906^[3]).

Iron: ferritin and transferrin saturation

Hidden iron overload is a common cause of liver damage. The first thing to change is transferrin saturation (TSAT): it is considered high above 45% in women and above 50% in men, and after menopause the male thresholds apply. High TSAT and ferritin are a reason to discuss testing the HFE gene with a doctor. Blood for saturation is drawn in the morning; fasting does not improve diagnosis (EASL. J Hepatol 2022. PMID 35662478^[4]). You can calculate saturation with the calculator.

“One in 200” is the frequency of people with two copies of C282Y (in people of Northern European ancestry), not of carriers. But the disease does not develop in everyone: over 12 years documented iron-overload disease occurred in 28.4% of men (21 of 74) and 1.2% of women (1 of 84) with two copies of C282Y (Allen K J N Engl J Med 2008. PMID 18199861^[5]). Early diagnosis and treatment by phlebotomy can prevent cirrhosis, liver cancer, diabetes and arthropathy. Ferritin is an acute-phase protein: it rises with inflammation, alcohol and fatty liver, so a single high result is read together with TSAT.

Viruses and stiffness: hepatitis and elastography

Hepatitis C is checked at least once in life in all adults aged 18 and over (except settings with prevalence below 0.1%): antibodies first, then viral RNA from the same sample if positive. Antiviral tablets cure most people in 8–12 weeks (Schillie S MMWR 2020. PMID 32271723^[6]). Hepatitis B is checked with three tests (HBsAg, anti-HBs, total anti-HBc): they show current infection, past infection, or whether vaccination is needed. By CDC estimate, up to two thirds of people with hepatitis B may be unaware of it (Conners E E MMWR 2023. PMID 36893044^[7]).

Elastography measures liver stiffness. A result below 10 kPa with no other signs rules out advanced chronic liver disease, and the 3-year risk of complications is then no more than 1%; 10–15 kPa is suspicious, above 15 kPa highly likely. A result of 10 kPa or more is repeated fasting or supplemented with the FIB-4 index (Baveno VII. de Franchis R J Hepatol 2022. PMID 35120736^[8]). For fatty liver disease the cut-off to rule out advanced fibrosis is 8 kPa (Rinella M E Hepatology 2023. PMID 36727674^[2]).

What to do with the result

FIB-4 is calculated from age, ALT, AST and platelets: below 1.3 low risk, 1.3 to 2.67 intermediate, above 2.67 high. At 1.3 or more the next step is elastography. Calculate it with the FIB-4 calculator. If the cause is fatty liver disease, weight loss helps: 3–5% reduces liver fat, while improving inflammation and fibrosis usually takes more than 10% (Rinella M E Hepatology 2023. PMID 36727674^[2]).

See a doctor if ALT is repeatedly above 30 U/L in men or 19 U/L in women, transferrin saturation is high together with high ferritin, elastography is 10 kPa or more, or you have yellowing of the skin, pain or heaviness under the right ribs. Prescribed treatment is not changed on your own.

Bottom line

Together the ten tests give a picture no single marker can. Start with ALT, AST, GGT and bilirubin, check hepatitis B and C once, and add iron and elastography as your doctor asks. A normal ALT does not exclude liver disease, and a small deviation is more often fatty liver than something frightening.