Nonalcoholic Fatty Liver Disease (NAFLD/MASLD): Overview, Diagnosis, and Treatment

Nonalcoholic fatty liver disease (NAFLD) is the accumulation of excess fat in liver cells in people who don't drink alcohol in amounts that could account for it on their own (conventionally, under 20 g/day for women and 30 g/day for men), and in whom other causes of fatty liver have been ruled out. In 2023, international liver societies proposed renaming it MASLD (metabolic dysfunction-associated steatotic liver disease), better reflecting its true underlying driver and requiring at least one cardiometabolic risk factor (e.g., obesity, insulin resistance, hypertension, or dyslipidemia) for diagnosis.

The scale of the problem is larger than it might seem. A large meta-analysis published in Hepatology in 2023, covering data from 1990–2019, estimated the global prevalence of NAFLD at 30.05% of the adult population (95% CI: 27.88–32.32%) — with a clear upward trend across recent decades, closely tied to rising rates of obesity and type 2 diabetes worldwide.

NAFLD/MASLD isn't a single, uniform condition — it's a spectrum, with simple steatosis (fat accumulation in liver cells without accompanying inflammation) at one end, and steatohepatitis — formerly called NASH, now MASH (metabolic dysfunction-associated steatohepatitis) — at the other, where cell damage and inflammation join the fat accumulation itself. This distinction matters a great deal for prognosis: simple steatosis on its own usually follows a mild, slowly progressing course, while NASH/MASH carries a real risk of progressing to fibrosis, cirrhosis, and in some cases hepatocellular carcinoma.

Not everyone with simple steatosis will develop NASH, and not everyone with NASH will develop cirrhosis — but determining where a given patient sits on this spectrum is essential for deciding on further management and follow-up frequency. That's why modern NAFLD/MASLD diagnosis increasingly focuses not just on confirming the presence of fat in the liver (relatively easy to do), but on assessing the degree of fibrosis, which correlates best with long-term prognosis.

In practice, this means a primary care doctor can make an initial estimate of advanced fibrosis risk in a patient with suspected NAFLD/MASLD (e.g., steatosis incidentally found on an abdominal ultrasound, or elevated liver enzymes) using a simple calculation from routine blood tests, without needing to immediately refer every patient for an invasive biopsy. Liver biopsy remains the reference method for ambiguous cases or when another, coexisting liver disease is suspected, but it's no longer the first diagnostic step.

Unlike many other chronic liver diseases, NAFLD/MASLD has a well-documented, effective non-pharmacological intervention — weight loss. The relationship between the amount of weight lost and the degree of improvement in the liver is clearly dose-dependent, making it one of the few chronic diseases where a specific, measurable weight target translates directly into hard liver-tissue endpoints rather than just intermediate markers.

Lifestyle modification — combining a calorie deficit, regular physical activity, and improved diet quality — remains, as AASLD guidance emphasizes, the cornerstone of NAFLD/MASLD/MASH management, even in the era of new pharmacological treatments. That doesn't mean pharmacotherapy is irrelevant — for patients with more advanced disease it's a meaningful addition, not a replacement for lifestyle change.

For many years, NAFLD/MASLD remained a disease without an approved pharmacological treatment aimed directly at the liver — lifestyle change and management of coexisting conditions remained the foundation. That's changing: resmetirom became the first FDA-approved drug specifically for patients with MASH and F2–F3 fibrosis, and semaglutide (better known as a drug used for type 2 diabetes and weight loss) has shown a favorable effect on liver histology in clinical trials of patients with moderate-to-advanced fibrosis.

In some patients with untreated or poorly controlled MASH, the disease progresses through successive stages of fibrosis to cirrhosis — a state in which normal liver tissue is permanently replaced by scar tissue, impairing organ function. In recent years, NAFLD/MASLD has become one of the leading causes of liver cirrhosis worldwide, overtaking viral hepatitis as the main driver in many regions. We cover the causes, stages, and symptoms of liver cirrhosis in detail in a separate article.

NAFLD/MASLD is a disease where the gap between the scale of the problem and public awareness is unusually large — it affects nearly one in three adults, yet most people with the diagnosis find out about it by accident, during tests done for a completely different reason. The good news is that, unlike many other chronic liver diseases, we have a well-documented, dose-dependent intervention here — weight loss — available to every patient regardless of access to the newest drugs.

If you suspect you have NAFLD/MASLD (for example, based on incidentally detected steatosis on ultrasound or elevated liver enzymes) or have already been diagnosed, the key step is working out with your doctor where on the disease spectrum you sit — that determines both the urgency of further workup and a realistic treatment target.