MAFLD: A Metabolic Liver Disease with the Potential for Recovery

A Functional Medicine approach to restoring liver and metabolic health
A Systems Disease at the Crossroads of Endocrinology, Immunology, and Hepatology

From insulin resistance to steatohepatitis: why MAFLD demands early recognition

The liver is one of the body’s most versatile and vital organs, performing over 500 distinct functions — from regulating blood sugar and breaking down hormones to processing fats and neutralising toxins. Its influence extends across every physiological system.

Yet liver dysfunction can progress quietly, often without noticeable symptoms, until significant damage has already occurred. One of the most common — yet still under-recognized — conditions is MAFLD (Metabolic Associated Fatty Liver Disease): a metabolically driven form of fatty liver disease with systemic consequences and the potential for reversal when detected early.

What is MAFLD?

MAFLD is diagnosed when excess fat has built up in the liver alongside one or more of the following: overweight or obesity (BMI ≥25), type 2 diabetes, or markers of metabolic imbalance (such as elevated triglycerides, low HDL cholesterol, insulin resistance, or high blood pressure).

Since 2020, MAFLD has replaced the older term NAFLD (Non-Alcoholic Fatty Liver Disease). Unlike its predecessor, MAFLD uses positive diagnostic criteria, focusing on fatty liver combined with metabolic dysregulation — independent of alcohol intake.

This shift reflects a broader understanding: MAFLD rarely occurs in isolation. It develops through the interplay of insulin resistance, chronic low-grade inflammation, visceral fat accumulation, hormonal and endocrine disruption, mitochondrial stress, and gut dysbiosis.

A Gradually Unfolding Disease Process

Understanding the definition is important — but just as critical is recognising how subtly and progressively the disease can develop. Non-invasive imaging such as ultrasound or FibroScan can detect hepatic fat, though accuracy varies. Functional blood testing can reveal early signs of metabolic strain and inflammatory activity, even before conventional liver markers change.

In its early stages, MAFLD often presents without clear warning signs. Routine enzymes like ALT and AST can remain within normal limits for years. Meanwhile, fat accumulation within liver cells may quietly contribute to:

• Reduced insulin sensitivity, disrupting glucose control
• Elevated fasting glucose and triglycerides
• Persistent, unexplained fatigue that doesn’t improve with rest and is frequently misattributed to lifestyle factors
• A vague sense of fullness or pressure under the right ribcage
• Gradual increase in abdominal (visceral) fat
• Heightened risk for type 2 diabetes, cardiovascular disease, hormonal disorders, PCOS, and hypothyroidism

Without intervention, MAFLD can progress to steatohepatitis, then fibrosis, and in severe cases, cirrhosis. The good news: in many cases this process is reversible — especially if detected early.

Insights from Research

Scientific literature increasingly recognises MAFLD as a systemic disorder arising from the intersection of metabolic imbalance, immune activation, and gut–liver axis disruption.

Within this network, interleukin-6 (IL-6) plays a key role as a pro-inflammatory messenger. Produced by visceral fat and immune cells, IL-6 production is amplified by gut dysbiosis and increased intestinal permeability. In the liver, IL-6 activates Kupffer and stellate cells, fuelling inflammation, fibrosis, and impaired glucose handling (Hotamisligil, 2017). It also disrupts insulin signalling via SOCS3, worsening insulin resistance (Klover et al., 2003).

Meta-analyses show that targeted interventions — weight reduction, gut microbiome restoration, optimised sleep and circadian rhythm, stress regulation, and consistent physical activity — can significantly improve liver fat, inflammatory markers, and metabolic health (Koutoukidis et al., 2019). The emerging science of the gut–liver–brain axis further reveals how microbial and immune signals influence mood, cognition, and fatigue (Wan et al., 2022).

Recovery Is Possible: Systemic and Personal

MAFLD management requires more than symptom suppression. Because the liver is deeply integrated with metabolic, hormonal, and immune networks, effective recovery hinges on addressing the root causes: insulin resistance, inflammation, hormonal imbalance, mitochondrial stress, and gut-related dysfunction.

At DNA Care, we take a Functional Medicine approach, mapping these factors through comprehensive blood work, microbiome analysis, genetic testing, and evaluation of epigenetic influences. Based on your unique profile, we design a personalized plan aimed at:

• Improving insulin sensitivity
• Regulating inflammatory pathways
• Supporting liver and mitochondrial resilience
• Restoring gut barrier integrity and microbiome balance
• Optimizing sleep, nutrition, physical activity, and stress response

The Liver as a Mirror of Systemic Health

MAFLD is not simply a “liver problem”; it is a reflection of systemic imbalance. The liver responds to signals of metabolic stress — such as insulin resistance, inflammation, hormonal disruption, and gut dysbiosis — but it also holds a remarkable capacity for regeneration.

Recognizing these stress signals early, and understanding what the body is trying to adapt to, creates the opportunity not just for halting damage, but for reversing it.

The liver is the only organ capable of fully regenerating functional tissue, even after substantial injury. Given the right conditions, hepatocytes can proliferate, restoring both liver mass and function. This regenerative capacity makes early detection of MAFLD and proactive treatment a powerful opportunity — turning a diagnosis into a gateway for restoring systemic health.

Have You Been Diagnosed with MAFLD?

If MAFLD is suspected, or if you have related conditions such as diabetes, PCOS, or hormonal imbalance, we recommend evaluation by an endocrinologist or hepatologist. This ensures comprehensive assessment and allows our care to integrate seamlessly with your broader medical plan.

At DNA Care, we work in collaboration with your healthcare providers to analyse the underlying drivers of your condition — using advanced diagnostics and system-wide insights — with the goal of restoring both liver health and quality of life.

MAFLD is not the end of health; it is an invitation to restore balance. By addressing the root causes now, you can not only halt progression but also reclaim liver health — and with it, your overall vitality and quality of life.

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