Diseases & Longevity · File 18

Fatty liver. The silent disease of 25-30% of adults — and the hepatic manifestation of the cardiometabolic cluster.

Non-alcoholic fatty liver disease — renamed MASLD (metabolic dysfunction-associated steatotic liver disease) in 2023 — affects approximately 25-30% of adults globally. It's asymptomatic until advanced stages but the real risk is not only hepatic: the main cause of death in MASLD is cardiovascular, not hepatic. It is the hepatic manifestation of the cardiometabolic cluster.

Why fatty liver is really a cardiovascular disease

Fatty liver was classically understood as an isolated hepatic condition. Modern evidence has redefined it as the hepatic manifestation of the cardiometabolic cluster — strongly associated with insulin resistance, dyslipidemia with elevated ApoB and small dense particles, hypertension, and central obesity. That explains why main MASLD mortality is cardiovascular, not hepatic.

The nomenclature change — NAFLD → MASLD, proposed by AASLD, EASL, and ALEH in 2023 — formalizes that reading. MASLD requires at least one cardiometabolic criterion (overweight/obesity, prediabetes/diabetes, hypertension, dyslipidemia). That clinical formalization reflects exactly what longevity medicine already did: treat fatty liver as part of the cluster, not as an isolated entity.

Fatty liver is not a liver problem — it is the hepatic footprint of a cardiometabolic cluster that kills via cardiovascular cause.
Global prevalence · Younossi 2023

The global weight, in numbers

Quantitative MASLD data come from global meta-analyses (Younossi), AASLD/EASL/ALEH guidelines, and longitudinal cohorts quantifying CV vs hepatic mortality.

  • Global prevalence

    ~25-30% adultos

    Approximately 25-30% of adults globally have MASLD — with higher prevalence in regions with high cardiometabolic burden (Middle East, Latin America, US). In T2D patients exceeds 50-70%.
    — Younossi et al., Hepatology 2023

  • CV > hepatic mortality

    Principal causa muerte MASLD

    In patients with non-advanced MASLD, cardiovascular mortality exceeds liver-related mortality. That reinforces the reading of MASLD as a cardiometabolic cluster disease, not isolated.
    — Targher et al., J Hepatol 2016

  • Progression to MASH and fibrosis

    ~20% progresan

    Approximately 20% of MASLD patients progress to steatohepatitis (MASH) with significant fibrosis. Advanced fibrosis (F3-F4) predicts hepatic events and mortality. FIB-4 is the most useful screening tool.
    — AASLD Practice Guidance 2023

  • Reversibility with intervention

    −7% peso → reversión

    Sustained loss of 7-10% body weight significantly reverses steatosis and improves hepatic inflammation. Combined with exercise and metabolic profile improvement, it's the intervention with best evidence.
    — Vilar-Gomez et al., Gastroenterology 2015

Chap. 03 · Cardiometabolic hepatic

Impact on CV, metabolic, and quality-of-life trajectory

MASLD doesn't only affect the liver — it coexists with the cardiometabolic cluster and that determines real outcomes. Isolated view systematically underestimates risk.

  • Coexistence with T2D

    50-70% en diabéticos

    50-70% of T2D patients have concomitant MASLD. That coexistence amplifies CV risk and risk of progression to MASH/cirrhosis. SGLT2i and GLP-1 (semaglutide) have solid effect on both axes.
    — AASLD 2023; EASL 2024

  • Cancer risk

    Hepatocarcinoma + extra-hepático

    MASLD with advanced fibrosis significantly increases hepatocellular carcinoma risk. Additionally, MASLD is associated with higher risk of extra-hepatic cancers (colorectal, breast, prostate) — due to shared metabolic-inflammatory cluster.
    — Mantovani et al., Lancet Gastroenterol 2022

  • Sarcopenia and body composition

    Eje músculo-hígado

    Sarcopenia frequently coexists with MASLD — they share insulin resistance and inflammaging. Measuring body composition (not just weight) and muscle strength changes clinical reading.
    — Hong et al., Hepatology 2017

  • Quality of life and fatigue

    Subestimada habitualmente

    MASLD patients report fatigue, worse perceived quality of life, and worse functional performance — particularly when MASH or cardiometabolic comorbidity is present. SF-36 impact is real, though clinically underestimated.
    — Younossi Hepatology 2023

What we don't offer — and what we do

Wellness Care does not manage advanced MASH or cirrhosis. Management of F3-F4 fibrosis, hepatocellular carcinoma, decompensated cirrhosis, and liver transplant are the hepatologist's and hospital's responsibility. What we do is what the conventional system rarely integrates: the reading of MASLD as a cardiometabolic cluster manifestation, early fibrosis screening with FIB-4, and structured intervention on the cluster.

We evaluate patients with incidentally detected steatosis, high-risk cardiometabolic profile (T2D, central obesity, dyslipidemia, HTN), unexplained mild transaminase elevation, or clinical suspicion of MASH. Evaluation integrates: FIB-4, advanced lipid profile, HbA1c and insulin, body composition, inflammaging, and the 14 Lancet Commission factors. Coordination with hepatology when advanced fibrosis or established MASH is suspected.

MASLD is not just a liver problem. It is the hepatic footprint of the cardiometabolic cluster — and working the cluster changes both axes simultaneously.
How we measure it

How MASLD is evaluated
at Wellness Care

Hepatic + cardiometabolic + body composition + 14 modifiable factors profile. Coordination with hepatology when advanced fibrosis is suspected.

Advanced biomarkers

21 specialized panels across 8 clinical categories — biological age, inflammaging, metabolic profile, functional hormonal, microbiota. The quantitative layer.

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Functional medicine

Shared root causes — mitochondrial dysfunction, inflammaging, neuroendocrine dysregulation — before organ pathology.

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Bioregulatory medicine

Autonomic regulation, HRV, stress response. The functional trajectory that precedes clinical diagnosis.

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The Longevity Program

How this assessment integrates into the full program — from initial valuation to individualized protocol design under medical judgment.

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Featured evidence

Key evidence supporting this approach

Four publications structuring the modern MASLD conversation — 2023 nomenclature, CV mortality, intervention reversibility, and clinical guidelines.

«MASLD afecta a aproximadamente el 25-30% de los adultos a nivel global — es la enfermedad hepática del cluster cardiometabólico, no una entidad aislada.»
Hepatology · 2023
Younossi et al., Hepatology 2023
Epidemiología global MASLD
«En MASLD, la mortalidad cardiovascular supera a la mortalidad por causa hepática — eso debe orientar el abordaje clínico.»
J Hepatol · 2016
Targher et al., J Hepatol 2016
Mortalidad CV > hepática
«La pérdida sostenida de 7-10% del peso corporal revierte significativamente la esteatosis y mejora la inflamación hepática.»
Gastroenterology · 2015
Vilar-Gomez et al., Gastroenterology 2015
Reversibilidad con intervención

Frequently asked questions about MASLD

The most recurrent questions about fatty liver, new MASLD nomenclature, fibrosis screening with FIB-4, and why longevity medicine treats it as part of the cluster.

01

What changed with MASLD vs NAFLD nomenclature?

In 2023, international associations (AASLD, EASL, ALEH) proposed the nomenclature change:

NAFLD → MASLD (metabolic dysfunction-associated steatotic liver disease)

The change formalizes the cardiometabolic nature of the disease. MASLD requires:

· Hepatic steatosis +
· At least one cardiometabolic criterion:
  · Overweight/obesity
  · Prediabetes/diabetes
  · Hypertension
  · Dyslipidemia

The change reflects the mechanistic reading — it's not just a liver problem.

02

How is advanced hepatic fibrosis risk screened?

Modern screening uses FIB-4 (fibrosis-4 score) as first step, calculated from:

· Age
· AST, ALT
· Platelets

Interpretation:

· FIB-4 < 1.3 → low risk
· FIB-4 > 2.67 → high risk, requires specialist evaluation

Second-line:

· ELF (Enhanced Liver Fibrosis test)
· Hepatic elastography (FibroScan)

AASLD 2023 / EASL 2024 guidelines structure this algorithm in patients with T2D, obesity, or cardiometabolic cluster.

03

Which lifestyle interventions work in MASLD?

Interventions with best evidence:

· Sustained loss of 7-10% body weight → reverses steatosis, improves hepatic inflammation, reduces fibrosis (Vilar-Gomez 2015 Gastroenterology)
· Mediterranean diet with unsaturated fats and simple sugar / fructose reduction
· Structured aerobic and strength exercise → independently improves insulin sensitivity and steatosis
· Eliminate alcohol consumption — even light

04

Do GLP-1s (semaglutide) help in MASLD?

Yes, with growing evidence.

Clinical trials (Newsome 2021 NEJM) showed semaglutide significantly improves steatohepatitis (MASH) — a significant proportion of patients achieved histological resolution without fibrosis worsening.

Synergistic effects:

· Weight loss
· Metabolic improvement
· Hepatic improvement
· CV event reduction

Resmetirom (THR-β agonist) received FDA approval 2024 specifically for MASH.

Prescription decision belongs to the specialist.

05

When should I consult?

A structured assessment is worthwhile if:

· You were detected with fatty liver on ultrasound or incidental study
· You have T2D
· Central obesity
· Hypertension or dyslipidemia
· Mildly elevated transaminases without identified cause
· Family history of MASH/cirrhosis
· Multiple cardiometabolic cluster

The integrated assessment (hepatic + cardiometabolic) complements hepatology and endocrinology — does not replace them.

The cluster's hepatic footprint

MASLD is not just a liver problem — it is the hepatic footprint of the cardiometabolic cluster that kills via cardiovascular cause.

Screen fibrosis with FIB-4, evaluate the full cluster (ApoB, HbA1c, body composition, inflammaging), work the 14 Lancet Commission factors, and coordinate with hepatology when advanced suspicion. That changes both axes simultaneously.

Detected steatosis or cardiometabolic cluster?

Book a comprehensive hepatometabolic assessment

We evaluate hepatic profile (FIB-4, ELF when indicated, elastography when applicable), metabolic profile (HbA1c, insulin, HOMA index), advanced lipid profile (ApoB, Lp(a)), body composition, inflammaging, and cluster comorbidities. The assessment does not replace hepatology or endocrinology — it complements them.

Book hepatometabolic assessment