Non-alcoholic fatty liver disease — NAFLD, renamed in 2023 as metabolic dysfunction-associated steatotic liver disease (MASLD) to emphasise its metabolic roots — is now the most common liver disease in the Western world. Current estimates put its global prevalence at more than 30% of adults, up from about 25% a decade ago. This article uses the older, more familiar term NAFLD. Most people who have it don't know it. And the standard liver test on a routine check-up is surprisingly bad at detecting it.
What NAFLD actually is
NAFLD is the accumulation of fat in liver cells in people who drink little or no alcohol. It ranges from simple steatosis (fat accumulation without inflammation) to non-alcoholic steatohepatitis (NASH, now called MASH — fat plus inflammation and cell damage), which can progress to fibrosis, cirrhosis, and liver cancer.
The disease is tightly linked to insulin resistance and metabolic syndrome. In fact, many hepatologists now consider NAFLD to be essentially the liver manifestation of metabolic syndrome. If you have insulin resistance, there's a good chance your liver is storing fat it shouldn't be.
Why standard tests miss it
The standard liver function test — ALT, AST, GGT — can suggest liver damage, but it has a crucial limitation: ALT can be normal even in people with significant fatty liver disease. In a 2020 meta-analysis, about one in four people with NAFLD — and about one in five with NASH — had ALT levels within the normal range, and current guidelines stress that people with normal ALT can still have significant inflammation and advanced fibrosis.
Part of the problem is that the "normal" ALT ranges used by many labs are considerably higher than the healthy ranges derived from low-risk people. A widely cited study in healthy blood donors proposed upper limits of about 30 U/L for men and 19 U/L for women; the 2024 EASL-EASD-EASO guideline defines ALT as elevated above 33 U/L in men and above 25 U/L in women, and notes that even lower thresholds have been proposed.
A practical example
A 48-year-old man has an ALT of 38. His lab report marks this as "normal" (reference range 10–50). But by the thresholds used in current guidelines (above 33 U/L for men), this is elevated — and it should prompt a closer look at the liver. When reviewing results, it is worth asking whether they were interpreted against evidence-based thresholds or simply against the lab's default range.
The metabolic cascade
NAFLD doesn't just damage your liver. It is increasingly recognized as a cardiovascular risk marker. In a 2021 meta-analysis of 36 studies with about 5.8 million people, NAFLD was associated with roughly 45% higher risk of fatal or non-fatal cardiovascular events — independent of age, sex, adiposity, diabetes and other common cardiometabolic risk factors — and the risk rose with the severity of liver fibrosis. Whether the liver disease itself causes these events is not yet proven. The liver is not just a passive victim of metabolic dysfunction; it actively participates in driving it.
The progression from insulin resistance to fatty liver to cardiovascular disease follows a predictable cascade:
- Insulin resistance → the liver receives more fatty acids than it can process
- Excess fat accumulates in liver cells (steatosis)
- Inflammation begins (NASH)
- The liver produces more triglycerides, more inflammatory markers, more clotting factors
- Cardiovascular risk climbs even as liver enzymes look "normal"
A reasonable approach
A sensible work-up starts with ALT, AST, and GGT — but interpreted against the lower, evidence-based thresholds. If any are elevated (even mildly), or if markers such as HOMA-IR suggest insulin resistance, the logical next step is an abdominal ultrasound to directly visualize liver fat.
For people at risk — those with type 2 diabetes, abdominal obesity plus another metabolic risk factor, or persistently elevated liver enzymes — current European guidelines recommend estimating fibrosis risk first with the FIB-4 score, calculated from routine blood values. A low score is reassuring and is rechecked every one to three years.
If FIB-4 is not low, FibroScan (transient elastography) is the usual next step — a non-invasive test that measures liver stiffness, which correlates with fibrosis stage. This is the test that hepatologists use to decide whether someone needs closer monitoring or intervention. If you have risk factors such as excess weight, insulin resistance or type 2 diabetes, it is reasonable to ask your doctor whether these steps apply to you.
The good news: early-stage NAFLD is reversible. Weight loss of about 5% can already reduce liver fat. In a prospective study of people with biopsy-proven NASH, those who lost at least 10% of their body weight saw the steatohepatitis resolve in 90% of cases, and fibrosis regressed in 45%. But you have to know you have it first — and with normal-looking lab results on a standard panel, most people never find out.
References
- EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81:492-542.
- Rinella ME, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79(6):1542-1556.
- Ma X, et al. Proportion of NAFLD patients with normal ALT value in overall NAFLD patients: a systematic review and meta-analysis. BMC Gastroenterol. 2020;20:10.
- Prati D, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002;137(1):1-10.
- Mantovani A, et al. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(11):903-913.
- Vilar-Gomez E, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367-378.
This article is general information and not individual medical advice. Decisions about tests and treatment belong in a conversation with your own physician.