The Quiet Threat of Fatty Liver in Lean Individuals

Exploring Fatty Liver in Lean Individuals 

Although fatty liver disease has been on the rise over the last two decades, along with the increasing prevalence of obesity, it has also been observed that fatty liver disease is increasing among individuals with normal weight, defined as a body mass index (BMI) below 25 kg/m2 in Caucasians and below 23 kg/m2 in Asians. It is important to note that BMI is an imperfect measure of health and doesn’t account for ethnic and sex differences, so a more individualized approach for assessing disease status is needed. Approximately 10–20%  of individuals with NAFLD have lean NAFLD. Despite their lower BMI, these individuals may still have high body fat, particularly visceral fat, which accumulates deep within the abdomen and surrounds vital organs. While some visceral fat is essential for health, excessive amounts can pose a risk and contribute to the development of fatty liver disease. People with lean NAFLD typically have a smaller waist circumference and a more favorable metabolic profile characterized by lower levels of dyslipidemia, diabetes, hypertension, glycemia, and insulin resistance compared to obese individuals. Despite this advantageous phenotype, lean NAFLD patients may experience a worse outcome and faster disease progression.

Genetics, Lifestyle, and Environment 

No matter one’s weight, lifestyle factors such as diet, particularly high fructose and cholesterol intake, and low physical activity levels, contribute to the risk of developing NAFLD. Additionally, environmental factors such as air pollutants, and toxins related to landfills further exacerbate the condition. The interplay between genetics, lifestyle, and environment underscores the complexity of NAFLD development in lean individuals, including what type of lean NAFLD an individual may develop:

• Type 1: Defined by visceral adiposity, when a person has extra fat around their organs, and insulin resistance, when one’s body has trouble using insulin, even if their weight is normal. This makes it harder for the body to adapt to changes in metabolism compared to people without these traits.
• Type 2: Defined by monogenic diseases (controlled by one specific gene), which means that some lean people with NAFLD develop it due to their genetics. These genetic problems can directly lead to NAFLD. However, doctors might not think about these genetic causes when they diagnose lean individuals with NAFLD who don’t have extra fat around their organs. Instead, they might overlook this possibility and focus on other factors.

Genetic predisposition plays a significant role in the development of NAFLD in lean individuals. Specifically, a version of the PNPLA3 gene called the rs738409 variant is linked to NAFLD. Among Hispanics, this variant is more prevalent compared to the total population (46% vs. 33%) and increases the risk of fatty liver disease. 

• When compared to individuals from other ethnic groups, lean, non-alcoholic, non-diabetic, non-smoking Asian Indians are twice as likely to develop fatty liver disease, which suggests a poorer metabolic status.
•  Fatty liver disease in lean individuals accounts for a higher proportion of those with the disease in Asia than globally.
• In a recent study, of the lean participants, Asian Americans accounted for 48.7%, although they only comprised 12.9% of the study population.

Diagnosis and Management Strategies

Without the most common risk factors, it can be hard for someone lean and without diabetes (or their doctor) to realize they have fatty liver disease.  For lean individuals, specific diagnostic approaches, including, imaging techniques and liver function tests, might help you check. The current, diagnostic path is similar to traditional NAFLD including a general exam, blood tests, imaging tests, and sometimes a liver biopsy. Measuring your waist circumference might be a better way to assess your risk, as Dr. Hanouneh and Dr. Kirkpatrick, authors of Skinny Liver and Regenerative Health, noted in a recent episode of GLI LIVE. They explain that waist circumference reflects visceral adiposity, which is the most dangerous type of fat, and related to fatty liver disease. They advocate for treatment approaches focusing on enhancing overall fitness and reducing visceral fat through weight loss strategies. While promising drugs are being developed and tested for fatty liver disease, including lean individuals, many questions remain unanswered. Clinical trials are essential to determine how effective these potential treatments are for managing NAFLD in lean patients.

If you’re a lean individual, it’s important to pay attention to fatty liver disease. People in this category aren’t considered “high risk” and might discover the disease at later stages, which can lead to a worse outlook. Even with a lower BMI and a smaller waist circumference, some people may still have a higher risk of developing NAFLD due to genetics, lifestyle, and environment. As lean NAFLD gains recognition, it’s crucial to have personalized ways to diagnose and manage it. Further research is needed to understand the factors and communities most closely tied to this condition. For more info on NAFLD/NASH in lean individuals, check out Global Liver Institute’s patient guide.

About Global Liver Institute  

Global Liver Institute (GLI) is a 501(c)3 nonprofit organization founded in the belief that liver health must take its place on the global public health agenda commensurate with the prevalence and impact of liver illness. GLI promotes innovation, encourages collaboration, and supports the scaling of optimal approaches to help eradicate liver diseases. Operating globally, GLI is committed to solving the problems that matter to liver patients and equipping advocates to improve the lives of individuals and families impacted by liver disease. GLI holds Platinum Transparency with Candid/GuideStar, is a member of the National Health Council, and serves as a Healthy People 2030 Champion. Follow GLI on Facebook, Instagram, LinkedIn, and YouTube or visit www.globalliver.org. Learn more about the Liver Health is Public Health program here.