Fatigue in NAFLD and NASH: How can fatty liver patients find their energy again?

What is fatty liver disease, and who is at risk?

Non-alcoholic fatty liver disease (NAFLD) occurs when excess fat builds up in the liver of people who drink little or no alcohol. It's one of the most common liver conditions worldwide, affecting about one in four adults globally. A more serious version of the condition, non-alcoholic steatohepatitis (NASH), involves inflammation and liver cell damage and can lead to fibrosis, cirrhosis, and even liver failure.

NAFLD and NASH are most common in individuals with obesity, type 2 diabetes, high cholesterol, or metabolic syndrome. While these conditions often develop silently, many patients experience an overwhelming, persistent sense of fatigue long before liver damage is visible through routine lab work.

In turn, fatigue profoundly impacts daily life. It can reduce a person's ability to work, exercise, and engage in social activities. NAFLD/NASH patients often report that their fatigue interferes with their motivation to follow through with recommended lifestyle changes such as physical activity and dietary improvements​​.

Fatigue is also frequently linked to mood disturbances, including depression and anxiety, compounding the emotional burden of living with a chronic condition​.

Why is fatigue so common in people with fatty liver disease? What does it indicate?

Fatigue is one of the most frequently reported symptoms among individuals with NAFLD and NASH. Studies suggest that up to 50% of patients with these conditions experience clinically significant fatigue, regardless of how advanced their liver disease appears on tests​.

This fatigue often involves both central and peripheral components:

• Central fatigue arises from the brain and nervous system. It’s associated with difficulty concentrating, low motivation, and a general sense of mental and emotional exhaustion. In people with NASH, chronic inflammation, altered neurotransmitter pathways, especially dopamine, and interactions between the liver and the brain have all been implicated​​.
• Peripheral fatigue affects the muscles and body. It can present as a lack of physical energy, reduced endurance, or muscle weakness. Research suggests that impaired muscle metabolism, especially in the later stages of liver disease, contributes to this form of fatigue​.

Importantly, fatigue in fatty liver disease does not always correlate with the degree of liver damage seen on imaging or blood work. In fact, recent studies suggest fatigue may be a more sensitive indicator of disease progression than some traditional clinical markers. New findings show that lower fatigue scores, indicating worse fatigue, are independently associated with an increased risk of liver-related complications, including cirrhosis and liver decompensation​.

This suggests that fatigue is not just a symptom; it may also be a red flag signalling worsening liver function and the need for closer monitoring.

Can fatigue be treated in fatty liver disease?

There is no single medication approved to treat fatigue in NAFLD or NASH. However, there are strategies that can help manage it:

• Treat the underlying liver disease: Lifestyle modifications, including weight loss through diet and physical activity, remain the most effective interventions for slowing disease progression. Even a 5–10% reduction in body weight can improve liver inflammation and fibrosis​.
• Address mental health: Depression and anxiety often overlap with fatigue. Treating these conditions, through counseling, medication, or support groups, can improve energy levels.
• Optimize sleep and physical activity: Sleep disorders are common in people with fatty liver. Improving sleep hygiene and incorporating gentle exercise may help alleviate both central and peripheral fatigue.
• Monitor and manage other conditions: Diabetes, thyroid disease, and anemia can all worsen fatigue and should be carefully controlled in patients with NASH.

Clinical trials are ongoing to test whether emerging drugs for NASH may also improve fatigue, offering hope for more targeted therapies in the future​.

Key takeaways

Fatigue is a common yet often overlooked symptom in people with non-alcoholic fatty liver disease (NAFLD) and its more advanced form, non-alcoholic steatohepatitis (NASH). It can arise from both central mechanisms, such as inflammation and brain-liver communication, and peripheral factors like muscle fatigue and reduced energy metabolism. Importantly, fatigue does not always correlate with the severity of liver test results but has been shown to predict disease progression, including cirrhosis and liver-related complications. Its presence can significantly affect daily functioning, emotional wellbeing, and quality of life. While there is no single treatment for fatigue in NAFLD/NASH, lifestyle changes, mental health support, and emerging therapies may help manage this symptom and improve long-term outcomes.

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