Liver Health and Longevity: Fatty Liver, How It Is Detected and What Helps
Fatty liver disease is common and often goes unnoticed. A 2016 meta-analysis put the global prevalence of what was then called nonalcoholic fatty liver disease at about 25% of adults,2 and in 2023 the condition was renamed metabolic dysfunction-associated steatotic liver disease (MASLD) to reflect its link with cardiometabolic risk factors.6 Here is what the evidence shows about testing, diet and the newest drug treatment.
- MASLD means fat build-up in the liver together with at least one cardiometabolic risk factor; under its earlier name, it affected about a quarter of adults worldwide in a 2016 meta-analysis.6,2
- A 2010 review argued that the liver handles fructose much like alcohol: both feed fat production in the liver and can promote insulin resistance and fatty liver.3
- In 76,113 Austrian adults, a marked rise in the liver enzyme GGT over seven years was linked to 40% higher cardiovascular death in men, independent of their starting GGT.4
- In the phase 3 ESSENCE trial, weekly semaglutide 2.4 mg resolved steatohepatitis without worsening fibrosis in 62.9% of patients versus 34.3% on placebo at 72 weeks.1
- Weight loss is part of the picture: patients on semaglutide in ESSENCE lost an average of 10.5% of their body weight.1
Fatty liver often causes no symptoms, which is why testing matters. By 2016, a meta-analysis estimated that fatty liver disease affected about 25% of adults worldwide.2
The Scope of the Problem
In 2023, a multisociety consensus renamed nonalcoholic fatty liver disease as metabolic dysfunction-associated steatotic liver disease (MASLD): fat in the liver together with at least one cardiometabolic risk factor.6 Under its earlier name, a 2016 meta-analysis estimated its global prevalence at about 25% of adults.2
The disease ranges from fat in the liver alone to steatohepatitis (MASH), in which inflammation and liver-cell injury are present and scarring (fibrosis) can develop. Drug trials have focused on people with MASH and moderate to advanced fibrosis (stage 2 or 3).1
Fructose and the Liver
Fructose gets particular attention because of how the liver processes it. A 2010 review argued that hepatic fructose metabolism resembles that of alcohol: both serve as substrates for fat production in the liver and, in the process, promote hepatic insulin resistance, abnormal blood lipids and fatty liver.3
The same review argued that fructose can also promote liver inflammation, through changes to proteins that generate superoxide. These are mechanistic arguments rather than trial results.3 Cutting back on sugary drinks is a simple way to reduce fructose intake.
Measuring Liver Health
Routine liver enzymes can offer clues. In a population cohort of 76,113 Austrian men and women followed for a median of 10.2 years, a marked rise in GGT (gamma-glutamyltransferase) over about seven years, more than 9.2 U/L, was associated with higher cardiovascular mortality in men (hazard ratio 1.40 compared with stable GGT), independent of baseline GGT and classical risk factors; the effect in women was smaller.4 ALT and AST rise when liver cells are injured.
Fat in the liver can be seen on ultrasound. Fibrosis risk can be estimated with the FIB-4 score, which combines age, AST, ALT and platelet count; you can calculate yours with our FIB-4 calculator. Liver elastography measures liver stiffness, which reflects fibrosis.
Semaglutide for MASH: What the Trials Found
In a 72-week phase 2 trial of 320 patients with NASH, daily semaglutide 0.4 mg resolved NASH without worsening fibrosis in 59% of patients versus 17% on placebo, but the improvement in fibrosis (43% versus 33%) was not statistically significant, and nausea, constipation and vomiting were more common with semaglutide.5 The phase 3 ESSENCE trial then randomized 1,197 patients with MASH and fibrosis stage 2 or 3 to weekly semaglutide 2.4 mg or placebo. In an interim analysis of the first 800 patients at week 72, steatohepatitis resolved without worsening fibrosis in 62.9% versus 34.3%, fibrosis improved without worsening steatohepatitis in 36.8% versus 22.4%, and body weight fell by an average of 10.5% with semaglutide.1
Put this research into practice: Biomarker Reference Tool
References
- 1Sanyal AJ, et al. "Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis." N Engl J Med. 2025;392(21):2089-2099. PubMed · DOI
- 2Younossi ZM, et al. "Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes." Hepatology. 2016;64(1):73-84. PubMed · DOI
- 3Lustig RH. "Fructose: metabolic, hedonic, and societal parallels with ethanol." J Am Diet Assoc. 2010;110(9):1307-21. PubMed · DOI
- 4Strasak AM, et al. "Longitudinal change in serum gamma-glutamyltransferase and cardiovascular disease mortality: a prospective population-based study in 76,113 Austrian adults." Arterioscler Thromb Vasc Biol. 2008;28(10):1857-65. PubMed · DOI
- 5Newsome PN, et al. "A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis." N Engl J Med. 2021;384(12):1113-1124. PubMed · DOI
- 6Rinella ME, et al. "A multisociety Delphi consensus statement on new fatty liver disease nomenclature." J Hepatol. 2023;79(6):1542-1556. PubMed · DOI
