Frequently asked questions — Hepatic steatosis
1) What does “hepatic steatosis” mean on ultrasound?
Hepatic steatosis refers to fat accumulation in the liver, frequently associated with cardiometabolic risk, such as obesity, T2DM, dyslipidaemia and hypertension, but it may also occur in the context of clinically relevant alcohol intake or secondary causes, including medications and concomitant liver diseases. The imaging finding requires aetiological assessment and fibrosis risk stratification, because disease severity is mainly determined by fibrosis, not merely by the presence of fat.
2) Do normal transaminases exclude relevant liver disease?
No. Normal values of AST and ALT, and even GGT, do not exclude significant fibrosis. For this reason, the current approach recommends non-invasive fibrosis stratification, such as FIB-4, in patients with steatosis, especially when cardiometabolic risk is present, to identify early those at risk of advanced fibrosis.
3) When should alcohol intake be quantified and why is it important?
Alcohol quantification is an essential step in the initial assessment, because intake above certain thresholds excludes classification as “pure” MASLD and requires consideration of a phenotype with clinically relevant alcohol exposure, such as ALD/MetALD. In practice, approximate values of >20 g/day in women and >30 g/day in men justify specific classification and targeted intervention for reduction/abstinence, without neglecting fibrosis assessment.
4) Which “alternative aetiologies” or secondary causes should be excluded?
Alternative or concomitant causes of steatosis should be excluded, including HBV/HCV, haemochromatosis, autoimmune hepatitis, Wilson disease and, in selected contexts, hypobetalipoproteinaemia and other causes. Endocrinopathies, such as hypothyroidism or hypopituitarism, catabolic states, such as starvation or parenteral nutrition, and lipodystrophies should also be considered. If an alternative aetiology is identified, targeted assessment and/or referral should be pursued, leaving the standard metabolic pathway.
5) Which medications may be associated with steatosis and how should they be managed?
Some medications may be associated with steatosis and/or liver injury, such as prolonged systemic corticosteroid therapy, amiodarone, methotrexate, tamoxifen, valproate and antiretroviral drugs. Their presence does not prove causality, but should prompt therapeutic review, weighing risks, benefits and alternatives, in coordination with the treating physician and/or relevant specialty.
6) What are “red flags” for advanced liver disease and what should be done?
These are clinical, laboratory or ultrasound findings suggestive of advanced liver disease or portal hypertension, such as unexplained thrombocytopenia, hypoalbuminaemia, prolonged INR, ascites, jaundice, encephalopathy, splenomegaly, collateral circulation/varices and structural ultrasound abnormalities, including a nodular/heterogeneous liver, irregular margins and hypertrophy of the caudate and/or left lobe. In the presence of these signs, priority referral to Gastroenterology/Hepatology should be arranged, without delaying assessment by applying serum scores.
7) What is FIB-4 and how is it interpreted?
FIB-4 is a non-invasive index that estimates the risk of advanced fibrosis using age, AST, ALT and platelet count. In general, a low value suggests low risk of advanced fibrosis, whereas intermediate/high values require second-line tests, such as FibroScan/VCTE or ELF, and/or specialist assessment. In patients aged ≥65 years, a higher low-risk threshold is often used, for example <2.0.
8) When should FibroScan or another second-line test be requested?
FibroScan (VCTE) and/or ELF are recommended when FIB-4 is intermediate or indeterminate, and often also when it is high, to improve risk stratification and guide referral decisions. These tests help reduce unnecessary referrals and more reliably identify patients with significant fibrosis.
9) If FIB-4 is low, what follow-up is recommended?
In patients without red flags and with low FIB-4, follow-up can be performed in primary care, with intervention on lifestyle, including weight loss, diet and exercise, and strict control of cardiovascular risk. FIB-4 reassessment should be adjusted to cardiometabolic risk: in patients with T2DM or ≥2 metabolic risk factors, a shorter interval is recommended, such as 1–2 years; in those with lower metabolic risk, 0–1 factor and no T2DM, longer intervals may be used, such as 2–3 years.
10) What should be prioritized in treatment in primary care?
Treatment is based on structured lifestyle intervention, including weight loss, diet and exercise, and above all optimization of cardiometabolic risk, including control of T2DM, hypertension and dyslipidaemia, with statins when indicated. Alcohol reduction is recommended and is a priority when clinically relevant intake is present. The aim is to reduce global cardiovascular risk and prevent progression to advanced fibrosis.
