What You Need To Know About Nonalcoholic Fatty Liver Disease

What is nonalcoholic fatty liver disease?

Nonalcoholic fatty liver disease (NAFLD) is caused by fat buildup in the liver, your body's largest solid internal organ. Your liver is located in the upper right section of your abdomen, below your rib cage and lungs.

A normal liver weighs about 3 to 3.5 pounds and averages 5.5 inches long, but as fat builds up, your liver can enlarge – a condition called ‘hepatomegaly’. NAFLD is the most common cause of liver function test abnormalities in the Western world. It is estimated that up to 46% of the US population has the condition.

People with NAFLD tend to consume little to no alcohol and have no other identifiable cause for the fat buildup, such as infection or autoimmune diseases. Although no one knows exactly what causes NAFLD, it's often associated with other medical issues like diabetes, obesity, and high cholesterol. Genetics may also play a role in its development. It’s mostly identified in people over 40 years old.

There are two types of nonalcoholic fatty liver disease:

  • Simple fatty liver – The liver has fat deposits in it, but there's no damage to liver cells and no inflammation. This is likely to result in mild liver dysfunction with no other consequences.

  • Nonalcoholic steatohepatitis (NASH) – Fat infiltrates the liver cells to the point of damaging them, leading to inflammation.

Most people with NAFLD have a simple fatty liver that does not progress to NASH. Without intervention, NASH can lead to cirrhosis (permanent scarring of the liver), liver failure, and liver transplantation.

There are numerous clinical trials available researching the latest treatments and medications to help those with NAFLD or NASH to live better quality lives.

Statistics

It's estimated that 100 million Americans will develop nonalcoholic fatty liver disease by 2030, costing $103 billion every year.¹ Also, NASH is projected to be the main cause of liver transplantation in the United States by 2030.

According to current statistics from the University of Michigan’s Nonalcoholic Fatty Liver Disease Program:

  • 30% (about 80 million) of Americans have NAFLD, with higher rates in Hispanics and Asians

  • 20% (about 15 million) of those Americans with NAFLD have NASH

  • 20% (about three million) of those Americans with NASH will develop cirrhosis

Nonalcoholic fatty liver disease is now the most common type of liver disease in children.

Symptoms

People with NAFLD typically have no symptoms and don't find out that they have it until it shows up by accident during imaging or blood tests¹. Your blood tests can reflect normal, rather than elevated, liver enzymes.² Occasionally some people will complain of fatigue or right-side abdominal pain, but most remain asymptomatic.

However, if NAFLD progresses to more advanced NASH liver failure, the following physical symptoms may occur:³

  • Abdominal swelling due to fluid collecting in abdominal spaces (ascites)

  • Enlarged esophageal blood vessels (varices)

  • Yellowing of the skin and eyes (jaundice)

  • Red palms

Imaging with ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) may reveal:

  • Enlarged liver

  • Enlarged spleen

  • Inflammation

  • Progressive fibrosis resulting in cirrhosis

  • Hepatic cancers related to NASH cirrhosis

NASH, left untreated, is associated with an increased risk of heart disease and stroke. Liver failure due to NASH cirrhosis can ultimately require a liver transplant.⁴

  1. Comprehensive Metabolic Panel (CMP) | Testing.com

  2. Elevated liver enzymes | Cleveland Clinic

  3. Symptoms of NASH | Fatty Liver Foundation

  4. What is a MELD score? | University of Pittsburgh Medical Center (UPMC)

Causes

Genetics, obesity, and lifestyle are thought to be major contributors to NAFLD. Although NAFLD is common, the disorder is complex as many factors can contribute to its development. There is an increased risk of NAFLD in families, but science does not know the inheritance pattern as yet.

Poor diet, poorly managed diabetes, obesity, smoking, and alcohol can contribute to the development of NAFLD. It is important to note that not all obese patients will develop fatty liver disease, and people with a normal body mass index (BMI) can also develop NAFLD.

Metabolic syndrome

Those with NAFLD often have higher levels of the hormone insulin, but suffer from insulin resistance. Insulin resistance means that your cells become resistant to the action of insulin.

People with NAFLD often have metabolic syndrome. This is defined as having three or more of the following characteristics:

  • Obesity with a BMI equal to or less than 30 – particularly those with abdominal obesity or an "apple-shape"

  • Prediabetic or type 2 diabetes

  • Low levels of good cholesterol (HDL)

  • High triglycerides (lipids)

  • High blood pressure

Metabolic syndrome is a key risk factor for both NAFLD and NASH.

NAFLD can also be associated with just one of the factors of metabolic syndrome.

NASH risk factors

The risk factors that result in the progression of NAFLD to NASH are:

  • Ongoing moderate to heavy alcohol use

  • Uncontrolled metabolic syndrome risk factors

  • Being over 50 years old at diagnosis

Interestingly, coffee consumption may help reduce the risk.¹

Diagnosis

There is no single test to diagnose fatty liver disease, nor is it a diagnosis of exclusion (the diagnosis that remains once all other possibilities have been eliminated). Your primary care physician or liver specialist (hepatologist) will take into account your patient history and whether you are at high risk for NAFLD consideration.

Initial screening entails blood tests and ultrasound imaging. Ultrasound can be all that is needed to diagnose NAFLD. A CT scan and MRI may also be used but may not be as good at detecting scarring.

There are four stages of fatty liver disease:

  1. Simple fatty liver – Also called ‘steatosis’, this is the earliest stage of NAFLD and the easiest to reverse.

  2. Nonalcoholic steatohepatitis (NASH) – This develops when cell damage and inflammation occur. This stage is reversible.

  3. Fibrosis or scarring – If enough scarring occurs, liver function is affected. Depending on the amount of fibrosis and the patient's overall health, this stage may be reversible or the progression of liver damage may be limited.

  4. Cirrhosis is the final stage of NAFLD. The liver ceases to work properly, increasing symptoms like pain and jaundice. It is not reversible. Cirrhosis can lead to liver transplantation.

Liver biopsy

Currently, a liver biopsy is the only definitive way to diagnose if someone has progressed from NAFLD to NASH.² A biopsy can also determine the extent of your liver damage and measure how much scar tissue (fibrosis) there is. It is an invasive test where a thin needle is inserted through your abdomen into your liver.

Given the risks associated with this procedure, it is mainly carried out if:

  • History and imaging cannot ascertain whether NAFLD is present

  • There are signs of liver failure

  • The patient is at high risk of progression (obesity/diabetes)

A small piece of liver tissue is removed and examined under a microscope.

The FibroScan test

Noninvasive, but less accurate, tests like transient elastography (FibroScan) can determine liver damage and scar tissue. The test determines the amount of scarring in your liver by measuring its stiffness and fat build-up (steatosis).

Your fibrosis score informs your healthcare provider what kind of treatment should begin or if there should be any changes to current treatment.

Although FibroScan is less accurate in severely obese people, the test can be repeated periodically to track the progression of NAFLD over time.

Measuring steatosis

FibroScan measures the amount of fatty change in your liver and gives it a grade, known as a controlled attenuation parameter (CAP) score. This is your steatosis grade and amount of liver fatty change:

  • S1 – CAP score ranges from 238 to 260 decibels per meter, affecting 11%–33% of your liver

  • S2 – CAP score ranges from 260 to 290 decibels per meter, affecting 34%–66% of your liver

  • S3 – CAP score exceeds 290 decibels per meter, affecting 67% or more of your liver

CAP scores can be used as a screening method for NAFLD when a liver biopsy is not needed or when there is no clear reason for a liver biopsy. CAP measurements taken at the same time as fibrosis scoring can provide healthcare providers with a clearer picture of your NAFLD stage.

NAFLD fibrosis score

A fibrosis score³ identifies the stage of your nonalcoholic fatty liver disease and if your fatty liver has advanced to fibrosis. There is an online calculator⁴ that allows you to calculate your fibrosis score:

  • F0 to F1 – No liver scarring to mild liver scarring

  • F2 – Moderate liver scarring

  • F3 – Severe liver scarring

  • F4 – Advanced liver scarring or cirrhosis

The one caveat with fibrosis scoring is that it can be overestimated. Overestimation is dependent on situations that can increase the stiffness of the liver without being due to scarring. Some of these include:

  • Viral hepatitis

  • Liver cancers

  • Congestion due to heart failure

FibroScan inaccuracies can also happen if your BMI is greater than 30 if you have fluid build-up or ascites in your abdomen, or biliary obstruction (too little bile flow from your liver).

Many larger hospitals have fatty liver clinics which allow for further investigation into your NAFLD or NASH and can provide insight into treatment options.

Treatments

Treatments include lifestyle modification and avoiding or limiting alcohol consumption. It's also important to manage your other diseases if you have high blood pressure, heart issues, or diabetes.

If you have NAFLD, changing your lifestyle is your first line of treatment.

Lifestyle modification

There are no medications that specifically cure NAFLD. With lifestyle modifications, however, the disease can be reversed as long as you have not progressed to cirrhosis.¹

Bear in mind, though, that every patient has a unique genetic makeup, so not everyone’s NAFLD is reversible. However, reducing the amount of fat and inflammation in your liver is possible by adopting a healthy diet and increasing physical activity.

You only need to lose 10% of your total body weight to see a reduction in liver fat and inflammation. But don't lose weight too quickly as rapid weight loss can actually make NAFLD worse. Aim to lose one to three pounds weekly by watching your diet and increasing your physical fitness.²

Your lifestyle changes do not have to be huge to make a positive difference to your NAFLD. In a group of obese patients, a weight-loss and exercise program resulted in 70% seeing a reduction in their scarring scores.³

Physical activity and fitness

Aim for 150 minutes of cardio per week. That amounts to 25 minutes every day with one day of rest. Aerobic exercise within your tolerance level strengthens your heart and lungs for better endurance.

Moderate-intensity activities like 30 minutes of brisk walking, bike riding, running, and swimming help your heart beat faster, so you breathe harder.

Add in stretching and strength activities two or three times a week as tolerated, for example:

  • Lifting weights

  • Using resistance bands

  • Repetitive exercise

Avoid using the same muscle groups on consecutive days and vary between moderate and intense workouts.

If you cannot tolerate much physical activity, work up to your goals. Any activity that gets your body moving helps you to achieve a higher level of fitness.

Most people can tolerate moderate physical activity. This is a lifestyle change that you should discuss with your doctor if you've not exercised regularly or have other health issues that need to be taken into account. Physical activity will also reduce cardiovascular mortality.

Tips for consistency in fitness

  • Simple changes like daily walks with an activity partner can keep you motivated.

  • Walk in increments if you are short on time. Just 10 minutes of walking three times a day can increase your fitness level over time.

  • Vary your exercise regimen.

  • Use a phone app to track your physical activity, check how many steps you take, or how many calories you are burning.

  • Remember, you are more likely to stick to your routine if you enjoy it.

NAFLD and the Mediterranean diet

Doctors recommend the Mediterranean diet for weight loss and fatty liver disease.⁴ This plant-based diet is also high in monounsaturated healthy fats like olive oil and nuts.

Fat makes up around 35%–45% of the Mediterranean diet's total energy intake. These fats are not the same fat that harms the liver. Monounsaturated fats contribute to weight loss, reduce the risk of heart disease, and decrease inflammation.

Carbohydrates constitute 35%–40% of the diet, while protein is just 15%–20%. The Mediterranean diet is high in omega-3 fatty acids which reduce the complications of nonalcoholic fatty liver disease.

The Mediterranean diet food pyramid breaks down as follows:

  • Eat vegetables, fibers, nuts, fruit, dietary products, and olive oil daily

  • Eat fish, seafood, poultry, eggs, and sweets weekly

  • Eat meat one to four times a month

Your plate should be filled with 50% fruit and vegetables. Whole grains like brown rice and whole-wheat pasta should be no more than 25% of your plate. Proteins like lean meat, fish, and legumes (beans) make up the other 25%.

If you would like red wine with dinner, consume no more than one glass. Any dairy should be low in fat. Also, limit sodium (salt) to no more than 2,400mg daily.

Remember: your portion sizes are 100% controllable, unlike serving sizes that are determined by the manufacturer.

If you cannot tolerate the Mediterranean diet due to food allergies or taste, concentrate on healthier eating habits to usher in a change of lifestyle. Your doctor may recommend a nutritionist to help you. A healthy diet can also help you better manage any other diseases that you may have.

Managing other diseases

Underlying diseases that contribute to nonalcoholic fatty liver disease should always be managed with the help of your primary care physician or your hepatologist. Do not stop any medications unless your doctor tells you to do so.

It can be tough to manage NAFLD with diet and exercise when other issues like high blood pressure, heart disease, or diabetes stipulate following a different regime, like the low-sodium, cardiac, or diabetic diet. A dietitian or nutritionist can help patients with more complex dietary needs.

Vaccinations

If you have liver disease, the following vaccinations are recommended by the Centers for Disease Control (CDC):

  • Flu

  • Pneumonia

  • Tdap (tetanus, diptheria, whooping cough)

  • Hepatitis A

  • Hepatitis B

  • Shingles

  • MMR (measles, mumps, rubella)

  • HPV

  • Chickenpox

Many people were vaccinated as a child or teen with the Tdap and chickenpox vaccines. Check with your doctor to see if a booster is recommended. Hepatitis A and B vaccinations are especially recommended for those with NAFLD or NASH.

Avoiding alcohol

Drinking moderate or heavy amounts of alcohol can further damage your liver and has been shown to result in progressive worsening of NAFLD. Ideally, those with NAFLD should avoid alcohol entirely as it is still not clear what a “safe” level of alcohol intake would be.

If complete abstinence is not possible, limit alcohol to a couple of drinks per day if you're a man and one drink per day if you're a woman.

Other potential treatments

There may be a role for Vitamin E in nondiabetics with NASH but as it has been associated with some increased mortality and prostate cancer, this should be discussed with your physician.

Other therapies currently being reviewed include:

  • The cholesterol medication Atorvastatin

  • Omega-3 fatty acids

  • Aspirin

Treatment advances

According to the International Liver Congress which met in June 2021, there have been new developments in the treatment of NAFLD.⁵

These include trials in:

  • Therapeutics

  • Antivirals

  • Structurally engineered fatty acids

Prevention

You can lower your risk of developing NAFLD by informing yourself of your options and being able to ask for what you want. Self-advocacy is important when you are affected by multiple diseases or disorders. For instance, besides your primary care physician, diabetes may be treated by an endocrinologist, blood pressure by a cardiologist, and abdominal issues by a gastroenterologist.

Your primary care physician and specialists need to work together with you as an interdisciplinary team to prevent NAFLD or NASH from worsening.

Diets rich in olive oil like the Mediterranean diet, not smoking, limiting or avoiding alcohol entirely, and regular exercise can prevent complications of NAFLD or even reverse it in its earlier stages.

Prognosis

Nonalcoholic fatty liver disease is often called the "silent disease" because most people do not realize that they have it. This can lead to unknown progression until a doctor happens upon it.

It is hard to give prognoses for NAFLD and NASH as each patient presents differently. Generally, though, disease progression is associated with uncontrolled risk factors.

Cirrhosis complications can include:

  • The development of large blood vessels (varices) that can rupture and bleed into your gastrointestinal tract

  • The accumulation of fluid in your abdomen (ascites) which can cause swelling and infection. If toxins can't be cleared away by your liver, they can build up in your bloodstream and travel to your brain causing confusion, behavior, and sleep changes (hepatic encephalopathy)

As cirrhosis progresses, there is also an increased risk of liver cancer.

Managing your cardiovascular risk factors is important as the highest cause of mortality in NAFLD and NASH is cardiovascular death.

NASH with cirrhosis is also associated with liver cancer and may need regular screening. This is best discussed with your physician.

Doctors & specialists

There is often an interdisciplinary team of healthcare professionals who treat nonalcoholic fatty liver disease or nonalcoholic steatohepatitis. These team members include both doctors and specialists who diagnose and treat it.

Doctors and specialists participating in NAFLD/NASH diagnosis

  • Your primary care physician or internist (doctor specializing in internal medicine) is often your first resource for NAFLD or NASH diagnosis through patient history, blood tests, and imaging. They can be either an MD (doctor of medicine) or DO (doctor of osteopathic medicine).

  • A hepatologist diagnoses, treats, and manages liver, gallbladder, bile duct, and pancreatic issues. They are a specialist.

  • A gastroenterologist specializes in all the digestive tract organs, including the liver.

Doctors and specialists participating in treatment

Other than your primary care physician, hepatologist, and gastroenterologist, you may see a nutritionist or dietitian for treatment.

  • Nutritionists help patients with general nutrition and their behaviors toward food. Many states now require nutritionist licensing, some do not.¹

  • Dietitians are trained to diagnose disorders like anorexia and bulimia, and to design diets to treat specific medical conditions.²

  1. Licensure Statutes and Information by State | Eat Right PRO

  2. Guidelines for credential placement | Commission on Dietetic Registration



Latest News

Clinical trials for nonalcoholic fatty liver disease

Actively recruiting
Metabolic Interventions to Resolve Non-alcoholic Steatohepatitis (NASH) With Fibrosis (MIRNA)
AZ, CA, CT, FL and 24 more locations (US)
Actively recruiting
Study Evaluating the Efficacy and Safety of Belapectin for the Prevention of Esophageal Varices in NASH Cirrhosis
AustraliaUnited States
Actively recruiting
A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis (MAESTRO-NASH)
AustraliaUnited States