Understanding fatty liver disease (MASLD) and MASH

What is MASLD — and what is MASH?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver condition in the world, affecting roughly 30% of adults worldwide — and a higher share of people with type 2 diabetes or obesity. It is defined by two things together:

• Steatosis — fat in at least 5% of liver cells, seen on ultrasound, CT, MRI, FibroScan (CAP) or biopsy; and
• At least one cardiometabolic risk factor — a BMI ≥25 (≥23 in people of Asian ancestry) or an enlarged waist; prediabetes or diabetes; blood pressure ≥130/85 or on treatment; triglycerides ≥150 mg/dL or on treatment; or low HDL cholesterol.

MASH (metabolic dysfunction-associated steatohepatitis) is the progressive, inflammatory subtype. Under the microscope, fat is joined by inflammation and "ballooning" injury of liver cells. MASH is what drives fibrosis — scar tissue laid down as the liver tries to repair itself.

The liver: the control center of metabolism

We tend to think of the liver as a filter. It is far more than that. The liver is where the body's fuel decisions are made, and it is exquisitely sensitive to hormones:

• Sugar. After a meal, insulin tells the liver to store glucose and stop making it. Between meals, glucagon tells it to release glucose. A fatty, insulin-resistant liver keeps pouring out glucose when it shouldn't — one of the central defects of type 2 diabetes.
• Fat and cholesterol. The liver builds new fat from sugar (de novo lipogenesis), burns fat for energy, and packages triglycerides and cholesterol into the particles (VLDL, then LDL) that circulate to the rest of the body — and into artery walls.
• Hormone signaling. Thyroid hormone, acting through the thyroid hormone receptor-β that dominates in the liver, drives fat burning and cholesterol clearance. Gut hormones such as GLP-1, and hepatokines the liver itself secretes (such as FGF21), fine-tune the system.
• Other roles — bile production, detoxification, clotting proteins, immune function — are preserved until scarring is advanced.

When fat overwhelms the liver, it stops responding normally to insulin, overproduces glucose and atherogenic lipoproteins, and releases inflammatory signals. That is why MASLD sits at the hub of a web of metabolic disease — type 2 diabetes, high triglycerides, low HDL, hypertension — and why the risk extends to the heart and kidneys (see Heart, Kidney & Liver).

The continuum: fatty liver → MASH → fibrosis → cirrhosis

MASLD is a spectrum, and movement along it goes both ways. Many people have simple steatosis for life; a minority develop MASH; some of those develop fibrosis; and a smaller number reach cirrhosis. What matters is that the early stages are often reversible — steatohepatitis can resolve and fibrosis can regress when the metabolic drivers are treated.

Three facts shape how we manage it:

• Fibrosis is the outcome predictor. Long-term studies of biopsy-proven disease show that fibrosis stage — not fat, inflammation or liver enzymes — predicts liver-related events and death. Compared with no fibrosis, liver-related mortality is roughly 10-fold higher at F2, 17-fold at F3, and over 40-fold at cirrhosis.
• Progression is unpredictable. Some patients progress about one stage every 7 years; a subset progresses much faster, especially with type 2 diabetes, older age, and ongoing weight gain.
• Enzymes can be normal. Most people with fibrosis in type 2 diabetes clinics have ALT and AST in the "normal" range, so normal liver tests do not rule out significant disease (see Diagnosis).

The new names: why NAFLD became MASLD

In 2023, the major liver societies replaced "nonalcoholic fatty liver disease" (NAFLD) and "nonalcoholic steatohepatitis" (NASH) with MASLD and MASH. The change was not cosmetic:

• It defines the disease by what causes it — metabolic dysfunction — rather than by what it is not (alcohol).
• It drops "fatty" and "nonalcoholic," terms many patients found stigmatizing.
• It creates MetALD for people with metabolic risk factors who also drink moderately (roughly 140–350 g of alcohol per week for women, 210–420 g for men) — acknowledging that both drivers often coexist.

Nearly everyone who had NAFLD meets the MASLD definition, so the decades of NAFLD/NASH research still apply. You will see both sets of names in older reports and papers.

How we grade evidence. Every intervention carries a plain label — from established, guideline-supported care (A) through moderate (B) and mixed or limited (C) to experimental (D) and insufficient (E). An improvement on a liver biopsy or scan is not the same as fewer cirrhosis cases, heart attacks, or deaths, and we say which we mean.