Nonalcoholic Fatty Liver Disease (NAFLD) Research Analysis

Q: What is NAFLD?

Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver diseases characterized by an excessive accumulation of fat in the liver without excessive alcohol consumption (i.e., > 21 standard drinks per week for men and > 14 standard drinks per week for women). It can be broadly divided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is less severe and only includes excessive liver fat (i.e., the presence of fat in > 5% of liver cells), whereas NASH includes excessive liver fat plus liver inflammation and damage.

Q: How are NAFLD and NASH different?

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are related, yet distinct, terms. NAFLD refers to a spectrum of liver diseases characterized by excess fat stored in the liver without excessive alcohol consumption or other secondary causes of fatty liver disease. Clinically, NAFLD is categorized as either simple fatty liver (NAFL) in which excess fat accumulation has occurred, but there is no evidence of cellular damage, or NASH, in which, in addition to the excess fat accumulation, inflammation of the liver (hepatitis), cellular damage (i.e., hepatocyte ballooning), and perhaps structural changes such as fibrosis are present. NASH occurs in about 20%[10] of people with NAFLD and is often thought of as the progressive form of NAFLD. We summarize how a healthy liver progresses through these steps in Figure 3.

Q: What is MAFLD?

In 2020, it was proposed in an international expert consensus statement to rename NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD).[11] This term has since been adopted by many, but not all, researchers and practitioners. The diagnosis of NAFLD is based on the presence of fat in >5% of liver cells in the absence of excess alcohol consumption and other known causes of liver disease. In MAFLD, a “positive criteria” is used to diagnose the disease, rather than relying on the exclusion of certain features. The diagnosis of MAFLD requires evidence of fat accumulation in the liver in addition to one of the following: overweight or obesity (defined as a BMI ≥ 25 kg/m2 or ≥ 23 kg/m2 in Asians), type 2 diabetes, or metabolic dysregulation as indicated by the presence of at least two metabolic risk abnormalities (i.e., high blood pressure, low HDL-cholesterol, elevated triglycerides, increased waist circumference, prediabetes, insulin resistance, or elevated levels of C-reactive protein (CRP; a marker of inflammation).[11] In addition, it’s suggested that MAFLD be used as a single overarching term, with disease severity described by the grade of activity and the stage of fibrosis, rather than the current system which categorizes cases as either NAFL or NASH.

Mike Murray

Nonalcoholic Fatty Liver Disease (NAFLD)

•Last Updated: August 16 2022

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excessive fat (more than 5% of liver weight) accumulates in the liver due to causes unrelated to alcohol.

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Nonalcoholic Fatty Liver Disease (NAFLD) falls under theLiver HealthandHealthy Aging & Longevitycategories.

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Mike Murray, RDN, CSCS, CISSN

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Morgan Pfiffner, MS • James Gaylor, MD, MPM

Last Updated: August 16 2022

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Frequently asked questions

What is NAFLD?

Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver diseases characterized by an excessive accumulation of fat in the liver without excessive alcohol consumption (i.e., > 21 standard drinks per week for men and > 14 standard drinks per week for women). It can be broadly divided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is less severe and only includes excessive liver fat (i.e., the presence of fat in > 5% of liver cells), whereas NASH includes excessive liver fat plus liver inflammation and damage.

How are NAFLD and NASH different?

What is MAFLD?

Which risk factors are associated with the progression of NAFLD?

Are lean individuals protected from NAFLD?

What are the main signs and symptoms of NAFLD?

Most people with NAFLD do not present with symptoms, and the disease remains silent until it has progressed to an advanced stage. In the early stages, fatigue and upper abdominal pain may be reported. Elevated levels of serum alanine aminotransferase and aspartate aminotransferase are also typically observed. In cases of very severe NAFLD, jaundice (i.e., yellowing of the eyes and skin), edema, ascites (i.e., excess fluid trapped in the abdomen), and/or confusion may be present.

How is NAFLD diagnosed?

Liver biopsy is considered the gold standard for diagnosing NAFLD and is essential for diagnosing NASH, as it is the only procedure that can reliably differentiate it from NAFL.^[1] Imaging methods, such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), are more commonly used, but their ability to detect mild NAFL is poor. MRI seems to be the precise imaging method.^[2]

What are some of the main medical treatments for NAFLD?

There are no Food and Drug Administration-approved medications for treating NAFLD. Current guidelines suggest that pharmacological treatment should be reserved for people with biopsy-proven NASH.^[3] Off-label medications are mainly used for treating risk factors (i.e., obesity, insulin resistance, hypertension, dyslipidemia) with the aim of preventing disease progression.

Have any supplements been studied for NAFLD?

Vitamin E seems to be the most compelling supplement for treating NAFLD.^[4] There is evidence to support the use of omega-3 polyunsaturated fatty acids as well.^[5]

Are there any other supplements that can help people with NAFLD?

How could diet affect NAFLD?

Lifestyle modification with the aim of inducing weight loss is the cornerstone of NAFLD treatment. A weight loss of at least 5% of initial body weight is effective for reducing liver fat, and a weight loss of 7–10% can improve features of NASH.^[3] In this respect, the macronutrient composition of the diet is much less important than the energy content; an array of dietary patterns can be effective as long as they facilitate sustained weight loss.

How could dietary fat affect NAFLD?

How could dietary protein affect NAFLD?

How could carbohydrate type affect NAFLD?

How could fruit affect NAFLD?

Is there a best diet for people with NAFLD?

Are there any other treatments for NAFLD?

An increase in physical activity is recommended alongside dietary changes to achieve significant weight loss.^[1]^[3] Exercise can also decrease liver fat irrespective of changes in body weight.^[6]

What causes NAFLD?

NAFLD reflects an imbalance of energy metabolism in the liver: more energy enters the liver than it can dispose of, resulting in a net accumulation of energy as triglycerides.^[7] Overnutrition and sedentary behavior primarily lead to the development of NAFLD, but there are a variety of other factors that further influence the development and progression of the disease, including genetics, aging, fat tissue dysfunction, gut dysbiosis, and insulin resistance.^[8]^[9]