Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (Fatty Liver Disease) — Formerly Non-Alcoholic Fatty Liver Disease (NAFLD)

If you arrived here searching for non-alcoholic fatty liver disease (NAFLD), fatty liver, or non-alcoholic steatohepatitis (NASH), you are in the right place. These are all names for the condition now formally called metabolic dysfunction-associated steatotic liver disease (MASLD). In 2023, the world's liver societies retired the old names: non-alcoholic fatty liver disease became metabolic dysfunction-associated steatotic liver disease, and its inflammatory form non-alcoholic steatohepatitis became MASH (metabolic dysfunction-associated steatohepatitis). The disease did not change. The name did — and the new name finally says what the illness actually is.

Metabolic dysfunction-associated steatotic liver disease means excess fat stored inside liver cells (steatosis, affecting more than 5% of hepatocytes) in a person who has at least one cardiometabolic risk factor — extra weight, high blood sugar, high blood pressure, high triglycerides, or low high-density lipoprotein (HDL). It is the most common chronic liver disease on earth. Most people who have it do not know, because for years it causes no symptoms at all.

Table of Contents

metabolic dysfunction-associated steatotic liver disease / fatty liver disease — scientific infographic poster
  1. The 2023 Name Change: Non-Alcoholic Fatty Liver Disease → Metabolic Dysfunction-Associated Steatotic Liver Disease
  2. The Disease Spectrum
  3. Pathophysiology: The Multiple-Hit Model
  4. Epidemiology
  5. Risk Factors and Genetics
  6. Symptoms and Clinical Presentation
  7. Diagnosis, FIB-4, and Elastography
  8. Treatment: Weight Loss, Diet, and Exercise
  9. Drug Treatment: Resmetirom and Glucagon-Like Peptide-1 Receptor Agonists
  10. Complications
  11. Prognosis and Surveillance
  12. Prevention
  13. Key Research Papers
  14. PubMed Topic Searches
  15. Connections
  16. Featured Videos

1. The 2023 Name Change: Non-Alcoholic Fatty Liver Disease → Metabolic Dysfunction-Associated Steatotic Liver Disease

In June 2023, a multi-society Delphi consensus — run under the auspices of the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL), in collaboration with the Latin American Association for the Study of the Liver (ALEH), with members of other societies, including the Asian Pacific Association for the Study of the Liver (APASL), among the panelists — formally replaced the old vocabulary. This is the single most important thing to understand about this disease right now, because it changes what you will read, what your doctor writes in your chart, and which search words bring up the newest research.

The old names and the new ones

Why the name changed

The rename was not cosmetic. It fixed two real problems with the old label:

  1. "Non-alcoholic" defined the disease by what it was not. Naming an illness for a substance the patient is not consuming is a diagnosis of exclusion dressed up as a diagnosis. It told you nothing about the mechanism, it pushed clinicians to think of the liver in isolation, and it made the condition sound like a lesser cousin of alcoholic liver disease rather than a metabolic disease in its own right.
  2. The word "fatty" was judged stigmatising. Patient advocacy groups involved in the consensus reported that the term was experienced as blaming and shaming, and that stigma discourages people from seeking care for a disease that is silent, common, and treatable when caught early.

The new name does the opposite: it names the actual driver — metabolic dysfunction. Metabolic dysfunction-associated steatotic liver disease is now a diagnosis of inclusion: it requires hepatic steatosis plus at least one cardiometabolic criterion. It is something you positively have, not something you merely fail to be.

The five cardiometabolic criteria

To diagnose metabolic dysfunction-associated steatotic liver disease, an adult needs steatosis on imaging or biopsy plus at least one of the following:

The wider family: SLD, MetALD, and ALD

The 2023 framework also built a house around the diagnosis. Steatotic liver disease (SLD) is the umbrella term for fat in the liver from any cause. Underneath it sit:

What the rename does not change

It is worth being clear about this, because the change has caused some confusion: the rename does not alter the underlying biology, the treatment, or the prognosis. A person with non-alcoholic fatty liver disease in 2022 and metabolic dysfunction-associated steatotic liver disease in 2026 has the same disease and needs the same care. What changes is the label, the diagnostic logic (inclusion rather than exclusion), and the recognition of MetALD. Note also that the great majority of people previously diagnosed with non-alcoholic fatty liver disease — around 98% in validation studies — also meet metabolic dysfunction-associated steatotic liver disease criteria, so the two populations overlap almost entirely.

A long transition is expected. Decades of research, drug trials, clinical guidelines, insurance codes, and electronic health records are indexed under non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Both vocabularies will appear side by side for years, which is why this page uses both.

A related term: MAFLD

You may also encounter MAFLD (metabolic-associated fatty liver disease), proposed by a separate international group in 2020. MAFLD and metabolic dysfunction-associated steatotic liver disease overlap heavily but are not identical: MAFLD requires steatosis plus overweight, diabetes, or metabolic dysregulation, and — unlike metabolic dysfunction-associated steatotic liver disease — does not exclude people with heavy alcohol intake. Metabolic dysfunction-associated steatotic liver disease is the term adopted by the 2023 multi-society consensus and is the one now used by AASLD and EASL guidelines.

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2. The Disease Spectrum

Metabolic dysfunction-associated steatotic liver disease is not one condition but a ladder of them, and the rungs carry wildly different risks. Understanding where you sit on this ladder matters more than any other single fact about your liver.

Steatosis (MASL) — simple fatty liver

Fat in more than 5% of liver cells, without meaningful inflammation or scarring. This is where most people with metabolic dysfunction-associated steatotic liver disease sit, and for most of them it stays that way. The annual risk of progressing to MASH is roughly 4%, and the ten-year risk of cirrhosis is low. Simple steatosis is not harmless — it still signals the metabolic trouble that drives heart disease — but on its own it is unlikely to destroy your liver.

Steatohepatitis (MASH) — the dangerous form

MASH is steatosis plus two things a pathologist can see: lobular inflammation and hepatocyte ballooning (liver cells swollen with injury). Roughly 20–30% of people with metabolic dysfunction-associated steatotic liver disease have MASH. This is the form that scars. It is graded with the non-alcoholic fatty liver disease Activity Score (NAS), which sums steatosis (0–3), lobular inflammation (0–3), and ballooning (0–2); a NAS of 5 or more, with at least one point in each category, is consistent with MASH. Fibrosis is scored separately — NAS measures current activity, fibrosis measures accumulated damage.

Fibrosis (F0–F4) — the stage that actually predicts your future

Scarring is staged from F0 to F4:

Here is the single most important prognostic fact in this disease: fibrosis stage — not the amount of fat, not the level of inflammation, not your alanine aminotransferase (ALT) — is what predicts liver-related death. This was established definitively by Angulo and colleagues, whose landmark study was titled, bluntly, "Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes," and confirmed by Ekstedt's cohort followed for up to 33 years and by Taylor's meta-analysis. In metabolic dysfunction-associated steatotic liver disease, fibrosis is the thing that kills you. Everything else is a means to that end.

Metabolic dysfunction-associated steatotic liver disease fibrosis begins in a characteristic place — a perisinusoidal, pericellular "chicken-wire" pattern around the central veins (zone 3) — which distinguishes it from the portal-based scarring of viral hepatitis.

Cirrhosis (F4)

Advanced, architecturally distorted scarring. Once cirrhosis develops, the complications of portal hypertension can follow: esophageal and gastric varices (dilated veins that can bleed catastrophically), ascites (fluid in the abdomen), spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy (confusion from ammonia the liver can no longer clear). Some fibrosis can regress with sustained treatment; established cirrhosis with architectural distortion is much harder to reverse, though it is no longer considered categorically irreversible.

Hepatocellular carcinoma (HCC)

Metabolic dysfunction-associated steatotic liver disease is now a leading cause of liver cancer in the United States and much of Europe. It carries one dangerous peculiarity: a substantial share of metabolic dysfunction-associated steatotic liver disease-related HCC arises in people who never developed cirrhosis. Published estimates of that share vary widely — from roughly 10% to as high as 40% depending on the population and how it was counted — and we would rather tell you the range honestly than invent a precise-sounding number. The clinical consequence is real either way: standard HCC surveillance is triggered by a cirrhosis diagnosis, so non-cirrhotic metabolic dysfunction-associated steatotic liver disease cancers are often found late. In MASH cirrhosis, the annual HCC risk is roughly 1–2%.

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3. Pathophysiology: The Multiple-Hit Model

The old explanation was the "two-hit" hypothesis: fat accumulates (hit one), then some insult — oxidative stress, a gut-derived toxin — inflames the fatty liver (hit two). It was elegant and it was wrong, or at least badly incomplete. The current framework is the "multiple parallel hits" model: many insults act at once, on a genetically susceptible person, and their combination determines who progresses from bland fat to inflammation to scar.

Insulin resistance and de novo lipogenesis

Insulin resistance is the central defect. It floods the liver with fat by three routes at once:

Lipotoxicity: why fat becomes injury

Stored triglyceride is comparatively inert — it is arguably the liver's attempt to render a toxic surplus safe. The damage comes from toxic lipid intermediates: ceramides, diacylglycerols (DAG), and lysophosphatidylcholine. Saturated fatty acids such as palmitate and stearate drive:

Dying hepatocytes release danger signals (DAMPs such as HMGB1 and extracellular vesicles) that recruit and activate Kupffer cells — the liver's resident macrophages — which pour out tumor necrosis factor-α, interleukin-1 beta (IL-1β), and interleukin-6 (IL-6).

The gut–liver axis

People with metabolic dysfunction-associated steatotic liver disease reliably show gut dysbiosis and increased intestinal permeability. A leakier gut lets bacterial products — lipopolysaccharide (LPS), lipoteichoic acid, and microbial metabolites — cross into the portal circulation and reach the liver directly. There they activate toll-like receptors (TLR4, TLR9) on Kupffer cells and stellate cells, and trigger the NLRP3 inflammasome. Altered bile-acid signalling through FXR adds another layer. The gut and the liver share a bloodstream, and in metabolic dysfunction-associated steatotic liver disease that intimacy works against you.

Fibrogenesis: how the scar forms

Hepatic stellate cells (HSCs) are the liver's fibrosis engine. Normally quiescent, storing vitamin A, they transform under chronic injury signals — TGF-β1, PDGF, leptin — into myofibroblasts that lay down collagen types I and III. Adipokine imbalance tilts the same way: leptin rises and promotes fibrosis, while protective adiponectin falls. The result is progressive, patterned scarring.

Genetics: why two people with identical waistlines get different livers

Genetics explain a substantial share of who progresses. Twin studies show high concordance even after adjusting for metabolic factors, and a handful of common variants do most of the work:

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4. Epidemiology

Metabolic dysfunction-associated steatotic liver disease is the most common chronic liver disease in the world, and it is still growing.

The most careful global meta-analysis (Younossi and colleagues, 2023, pooling 92 studies and over 9 million people) found an overall global prevalence of about 30% across the whole 1990–2019 study window — but the trend inside that window is the real story. Prevalence rose by roughly 50% in a single generation, from about 25.3% in 1990–2006 to about 38.0% in 2016–2019. The widely quoted "38% of adults" figure is that most-recent-period estimate, not the all-years average, and it is worth being precise about which is which.

Where it is worst

Prevalence by region, from the same analysis:

Who has it

Children

Pediatric metabolic dysfunction-associated steatotic liver disease is rising with childhood obesity and is now a serious public health problem in its own right, affecting an estimated 10% or so of children overall and a far higher share of children with obesity. Pediatric disease is not merely adult disease in a smaller body: the histology often shows a portal/periportal (zone 1) predominance rather than the adult zone 3 pattern, and progression can be faster.

Transplant

MASLD/MASH cirrhosis is among the leading indications for liver transplantation in the United States and is one of the fastest-growing. Given the trajectory of obesity and diabetes, it is widely projected to become the leading indication.

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5. Risk Factors and Genetics

Metabolic drivers

Hormonal and systemic contributors

Dietary and lifestyle

Genetic risk

The variants described in the Pathophysiology section — above all PNPLA3 I148M and TM6SF2 E167K, with MBOAT7 and GCKR adding risk and HSD17B13 loss-of-function conferring protection — are the best-established genetic determinants. Genetic testing is not currently standard of care, but it is plausible that PNPLA3 genotyping will eventually be used to stratify who needs closer surveillance, particularly for liver cancer.

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6. Symptoms and Clinical Presentation

Most people with metabolic dysfunction-associated steatotic liver disease have no symptoms whatsoever. Roughly 75–80% are entirely asymptomatic, which is precisely what makes this disease dangerous: it can scar a liver quietly for decades. It is usually discovered by accident — an ultrasound ordered for gallstones, a routine blood panel with a mildly raised alanine aminotransferase, a metabolic workup for diabetes.

When symptoms do appear

Signs of advanced disease

Once cirrhosis develops, the picture changes to that of end-stage liver disease: jaundice, ascites, peripheral edema, spider angiomata, palmar erythema, splenomegaly, muscle wasting, and hepatic encephalopathy (confusion, asterixis). Bleeding esophageal varices are a medical emergency.

A critical caveat about liver enzymes

Mildly elevated alanine aminotransferase and aspartate aminotransferase (AST) (typically 1–4 times the upper limit of normal, with alanine aminotransferase usually higher than aspartate aminotransferase — the reverse of alcohol-related disease, where aspartate aminotransferase:alanine aminotransferase commonly exceeds 2) are the usual laboratory trigger for investigation. But a normal alanine aminotransferase is not reassurance:

Normal liver enzymes do not exclude MASH, and they do not exclude advanced fibrosis or even cirrhosis. A large fraction of people with significant fibrosis have entirely normal transaminases. As fibrosis advances, the aspartate aminotransferase:alanine aminotransferase ratio tends to rise above 1 — because the alanine aminotransferase-producing hepatocytes are progressively being replaced by scar. A "normal" liver panel has sent an enormous number of people home with a disease they still have.

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7. Diagnosis, FIB-4, and Elastography

Diagnosis has three jobs: confirm there is fat, exclude other liver diseases, and — most importantly — find out whether there is fibrosis. That last job is what actually changes your future.

Initial evaluation

FIB-4 — the usual first test

The FIB-4 index is the workhorse of metabolic dysfunction-associated steatotic liver disease care. It is free, it uses labs you almost certainly already have, and it is recommended as the first-line fibrosis triage step by AASLD, EASL, AGA, and ACG:

FIB-4 = (Age × aspartate aminotransferase) ÷ (Platelet count × √alanine aminotransferase)

Age matters, and this is a common trap. FIB-4 contains age in its numerator, so it drifts upward with age all by itself. In patients over 65, the standard 1.30 lower cutoff produces far too many false positives — a lower threshold of about 2.0 and an upper threshold of about 3.25 are more appropriate. In patients under 35, FIB-4 performs poorly in the other direction. Applying adult-average cutoffs blindly across all ages is one of the most frequent errors in metabolic dysfunction-associated steatotic liver disease triage.

Transient Elastography and CAP

Vibration-controlled transient elastography (VCTE) measures liver stiffness in kilopascals as a proxy for fibrosis, and simultaneously reports CAP (controlled attenuation parameter, in dB/m) as a measure of fat. It is quick, non-invasive, and done at the point of care.

Caveats that matter in practice: readings are falsely elevated by recent eating (readings are taken after a fast of at least 2–3 hours), by active inflammation with high transaminases, and by hepatic congestion from heart failure. Severe obesity reduces reliability and may require the XL probe. A single high reading in a patient who just had lunch is not a diagnosis of cirrhosis.

Other non-invasive tools

When biopsy is still used

Liver biopsy remains the reference standard — it is still the only test that can definitively distinguish MASH from simple steatosis and stage fibrosis precisely. But it is invasive, it costs money, it carries a small but real risk of serious bleeding, and it samples perhaps one fifty-thousandth of the organ, so sampling error is genuine. It is no longer a routine part of diagnosis. It is reserved for when it will actually change what happens next:

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8. Treatment: Weight Loss, Diet, and Exercise

Lifestyle change is not the consolation prize you are offered while waiting for a real drug. It remains the foundation of treatment, it is the intervention with the best evidence for reversing fibrosis, and it has no side effects.

The weight-loss ladder — and the 7–10% threshold

The relationship between weight lost and liver healed is dose-dependent, and the numbers below are the most actionable in this entire article. They come principally from Vilar-Gomez's landmark 52-week lifestyle study and Promrat's randomised trial:

For a 200-pound person, 7–10% is 14–20 pounds. That is a hard target but a human one — and it is worth knowing that it is the liver threshold, not a cosmetic one. A standard approach is a deficit of roughly 500–1,000 kcal/day. Adherence matters more than the precise macronutrient split.

The Mediterranean diet

The Mediterranean diet has the strongest evidence of any dietary pattern in metabolic dysfunction-associated steatotic liver disease and is the pattern recommended in guidelines. Olive oil, fish, legumes, whole grains, vegetables, fruit, and nuts; little red meat, little processed food, little added sugar. Its most remarkable property is that it reduces liver fat even without weight loss — through monounsaturated fat, omega-3s, fibre that feeds a healthier microbiome, and polyphenols that act on PPARα, AMP-activated protein kinase (AMPK) and SIRT1 to push the liver toward burning fat rather than storing it.

Fructose and sugar-sweetened drinks

If there is a single highest-yield specific dietary change, this is it. Fructose is metabolised almost entirely in the liver and bypasses the regulatory checkpoint that limits glucose flowing into fat synthesis — so it drives de novo lipogenesis more or less unopposed, while also generating uric acid. Sodas, energy drinks, sweetened coffees, and fruit juice are the main sources. Whole fruit is fine: the fibre slows absorption and changes the whole picture.

Other dietary approaches

Exercise — and why it works even if you don't lose weight

This is one of the most encouraging facts in the disease: exercise reduces liver fat independently of weight loss. If the scale is not moving, your liver may still be improving.

Alcohol

Even moderate drinking accelerates fibrosis in someone who already has steatohepatitis. No safe threshold has been established in metabolic dysfunction-associated steatotic liver disease, and the MetALD category exists precisely because alcohol and metabolic dysfunction compound each other. The 2023 AASLD guidance states that patients with clinically significant fibrosis (stage F2 or worse) should abstain from alcohol completely, and that heavy drinking accelerates liver injury and fibrosis and should be avoided by anyone with the disease.

Supplements: what the evidence supports, and what it doesn't

Several nutrients and botanicals have a plausible mechanism and some human data in fatty liver. None is a substitute for weight loss, and the evidence for all of them is weaker than for the interventions above — mostly small trials using liver enzymes or imaging as endpoints, rather than biopsy-proven MASH resolution. With that honest framing:

Note the asymmetry running through this whole section: the interventions with the strongest evidence — losing 7–10% of your body weight, the Mediterranean pattern, exercise, cutting sugary drinks — are the ones nobody sells you.

Exposures linked to harm

Bariatric and metabolic surgery

For people with severe obesity who cannot achieve or hold the necessary weight loss, bariatric surgery is the most reliable route to sustained improvement. Roux-en-Y gastric bypass and sleeve gastrectomy both improve MASH histology, and Lassailly's long-term work has demonstrated durable MASH resolution and fibrosis regression years after surgery. It is contraindicated in decompensated cirrhosis, and requires careful risk–benefit judgment in compensated cirrhosis.

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9. Drug Treatment: Resmetirom and Glucagon-Like Peptide-1 Receptor Agonists

For decades this disease had no approved drug at all. That has changed twice in two years, and metabolic dysfunction-associated steatotic liver disease is now one of the fastest-moving areas in medicine.

Resmetirom — the first approved MASH drug

Resmetirom was approved by the U.S. Food and Drug Administration (FDA) in March 2024 — the first drug ever approved specifically for MASH. It received accelerated approval for use alongside diet and exercise in adults with non-cirrhotic MASH with moderate-to-advanced fibrosis (stages F2–F3).

Read those numbers honestly. Roughly a quarter of patients improved their fibrosis — against 14% who improved on placebo alone. This is a genuine, historic advance and it is not a cure. It works alongside diet and exercise, not instead of them.

Semaglutide — the second approved MASH drug

In August 2025, the U.S. Food and Drug Administration granted accelerated approval to semaglutide 2.4 mg for non-cirrhotic MASH with moderate-to-advanced fibrosis (F2–F3) — making it the first glucagon-like peptide-1 (GLP-1) receptor agonist approved for this disease. Many sources written before that date still say "no glucagon-like peptide-1 is approved for MASH." That is now out of date.

Note the important nuance on the earlier evidence: the well-known 2021 phase 2 semaglutide trial (Newsome and colleagues) used once-daily semaglutide 0.4 mg — not the weekly 2.4 mg dose — and while it produced striking MASH resolution (59% vs 17%), its fibrosis endpoint was not statistically significant (43% vs 33%, P=0.48). It was the larger phase 3 ESSENCE trial that finally demonstrated a fibrosis benefit. Sources that quote the phase 2 resolution figure as though the fibrosis question was settled in 2021 are overstating it.

Other Glucagon-Like Peptide-1 based agents

Older options that still have a role

What does not work, and what failed

The pipeline

Several agents are in advanced development, including lanifibranor (a pan-PPAR agonist, positive in the phase 2 NATIVE trial and now in phase 3) and FGF21 analogues such as efruxifermin. Given how quickly this field is moving, any list of "investigational" drugs — including this one — is perishable.

Managing everything else

Because cardiovascular disease is the leading killer in metabolic dysfunction-associated steatotic liver disease, aggressive treatment of blood pressure, low-density lipoprotein cholesterol, and glucose is not a side quest — it is central to treating this patient, whatever their fibrosis stage.

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10. Complications

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11. Prognosis and Surveillance

Prognosis is governed by fibrosis stage. Almost nothing else on the pathology report changes your outlook nearly as much.

Outlook by fibrosis stage

Across cohorts, each additional fibrosis stage carries a stepwise increase in liver-related mortality — the central finding of Angulo's cohort, Ekstedt's 33-year follow-up, and Taylor's meta-analysis.

How fast does it progress?

Slowly, and unevenly. On average, fibrosis advances roughly one stage every seven years in MASH — but the average conceals enormous variation. A large minority of patients never progress at all over years of follow-up, while others advance rapidly. Type 2 diabetes is the strongest predictor of fast progression. Progression is also not one-way: fibrosis can and does regress when the metabolic driver is removed.

One curiosity worth knowing: "burned-out" MASH. In some people who reach cirrhosis, the original steatosis and inflammation quietly disappear, leaving scar tissue with no fat and no MASH on biopsy. Their cirrhosis then looks "cryptogenic" — of unknown cause — when in fact metabolic dysfunction-associated steatotic liver disease caused it and then covered its tracks. A meaningful share of so-called cryptogenic cirrhosis is burned-out MASH.

Surveillance

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12. Prevention

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Key Research Papers

Every citation below has been checked against PubMed; the linked year/volume/pages resolves to the paper named.

  1. Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966–1986. — the paper that renamed the disease. — doi:10.1097/HEP.0000000000000520 · PubMed PMID: 37363821
  2. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797–1835. — doi:10.1097/HEP.0000000000000323 · PubMed PMID: 36727674
  3. European Association for the Study of the Liver (EASL), EASD, EASO. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). Journal of Hepatology. 2024;81(3):492–542. — doi:10.1016/j.jhep.2024.04.031 · PubMed PMID: 38851997
  4. Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis (MAESTRO-NASH). New England Journal of Medicine. 2024;390(6):497–509. — the trial behind the first approved MASH drug. — doi:10.1056/NEJMoa2309000 · PubMed PMID: 38324483
  5. Sanyal AJ, Newsome PN, Kliers I, et al.; ESSENCE Study Group. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. New England Journal of Medicine. 2025;392(21):2089–2099. — the trial behind the semaglutide approval. — doi:10.1056/NEJMoa2413258 · PubMed PMID: 40305708
  6. Loomba R, Hartman ML, Lawitz EJ, et al.; SYNERGY-NASH Investigators. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. New England Journal of Medicine. 2024;391(4):299–310. — a phase 2 trial, despite frequent misdescription as phase 3. — doi:10.1056/NEJMoa2401943 · PubMed PMID: 38856224
  7. Newsome PN, Buchholtz K, Cusi K, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. New England Journal of Medicine. 2021;384(12):1113–1124. — doi:10.1056/NEJMoa2028395 · PubMed PMID: 33185364
  8. Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN). The Lancet. 2016;387(10019):679–690. — doi:10.1016/S0140-6736(15)00803-X · PubMed PMID: 26608256
  9. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis (PIVENS). New England Journal of Medicine. 2010;362(18):1675–1685. — doi:10.1056/NEJMoa0907929 · PubMed PMID: 20427778
  10. Francque SM, Bedossa P, Ratziu V, et al. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH (NATIVE). New England Journal of Medicine. 2021;385(17):1547–1558. — doi:10.1056/NEJMoa2036205 · PubMed PMID: 34670042
  11. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367–378. — the source of the 7–10% weight-loss threshold. — doi:10.1053/j.gastro.2015.04.005 · PubMed PMID: 25865049
  12. Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121–129. — doi:10.1002/hep.23276 · PubMed PMID: 19827166
  13. Lassailly G, Caiazzo R, Ntandja-Wandji LC, et al. Bariatric surgery provides long-term resolution of nonalcoholic steatohepatitis and regression of fibrosis. Gastroenterology. 2020;159(4):1290–1301. — doi:10.1053/j.gastro.2020.06.006 · PubMed PMID: 32553765
  14. Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. Journal of Hepatology. 2017;67(4):829–846. — doi:10.1016/j.jhep.2017.05.016 · PubMed PMID: 28545937
  15. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389–397. — fibrosis stage is what matters. — doi:10.1053/j.gastro.2015.04.043 · PubMed PMID: 25935633
  16. Ekstedt M, Hagström H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547–1554. — doi:10.1002/hep.27368 · PubMed PMID: 25125077
  17. Taylor RS, Taylor RJ, Bayliss S, et al. Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis. Gastroenterology. 2020;158(6):1611–1625. — doi:10.1053/j.gastro.2020.01.043 · PubMed PMID: 32027911
  18. Younossi ZM, Golabi P, Paik JM, et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335–1347. — the source of the 30% pooled / 38% recent-period prevalence figures. — doi:10.1097/HEP.0000000000000004 · PubMed PMID: 36626630
  19. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease — meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. — doi:10.1002/hep.28431 · PubMed PMID: 26707365
  20. Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nature Reviews Gastroenterology & Hepatology. 2018;15(1):11–20. — doi:10.1038/nrgastro.2017.109 · PubMed PMID: 28930295
  21. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nature Genetics. 2008;40(12):1461–1465. — the PNPLA3 discovery paper. — doi:10.1038/ng.257 · PubMed PMID: 18820647
  22. Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nature Medicine. 2018;24(7):908–922. — doi:10.1038/s41591-018-0104-9 · PubMed PMID: 29967350
  23. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease (the NAFLD Activity Score). Hepatology. 2005;41(6):1313–1321. — doi:10.1002/hep.20701 · PubMed PMID: 15915461
  24. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317–1325. — the original FIB-4 paper. — doi:10.1002/hep.21178 · PubMed PMID: 16729309
  25. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–854. — doi:10.1002/hep.21496 · PubMed PMID: 17393509
  26. Eslam M, Sanyal AJ, George J, et al. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020;158(7):1999–2014. — doi:10.1053/j.gastro.2019.11.312 · PubMed PMID: 32044314
  27. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the AASLD. Hepatology. 2018;67(1):328–357. — doi:10.1002/hep.29367 · PubMed PMID: 28714183

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14. PubMed Topic Searches

These links open live PubMed queries — results update as new studies are indexed.

  1. Metabolic dysfunction-associated steatotic liver disease (MASLD)
  2. MASH / NASH treatment and fibrosis
  3. Non-alcoholic fatty liver disease (NAFLD, legacy term)
  4. Resmetirom for MASH with fibrosis
  5. Semaglutide and glucagon-like peptide-1 agonists in MASH
  6. FIB-4 score and non-invasive fibrosis assessment
  7. Transient elastography in fatty liver
  8. PNPLA3 and TM6SF2 genetic variants
  9. Insulin resistance and de novo lipogenesis
  10. Mediterranean diet and fatty liver
  11. MASLD, HCC, and non-cirrhotic liver cancer
  12. Fatty liver and cardiovascular mortality

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Connections

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