Navigating NAFLD: An Overview of Non-Alcoholic Fatty Liver Disease

What is Non-Alcoholic Fatty Liver Disease?

More often than not, fatty liver disease is pinned on chronic alcohol use. While alcohol use does lead to liver damage, surprisingly, it is not the most common cause. Non-alcoholic fatty liver disease (NAFLD) is currently the leading cause of liver disease in the world.

NAFLD, also known as metabolic fatty liver disease (MAFLD), is a condition in which excess fat builds up in the liver cells. At the cellular level, the development of NAFLD is closely related to the metabolic changes caused by obesity, type 2 diabetes, and high cholesterol. Although it doesn’t cause any immediate harm, NAFLD can lead to permanent liver scarring, called fibrosis.

Today, over 30% of the world’s population has NAFLD. In Canada, 10 million people, including children, have NAFLD. However, many people with the condition don’t even know they have it. Because NAFLD is underdiagnosed, the NAFLD epidemic has been flying under the radar for quite some time.

How and Why NAFLD Develops

The liver is an incredible multifunctional organ. But what the liver doesn’t do is store excess calories in the form of fat. In a person with NAFLD, however, more than 5% of the liver weight is composed of fat. How or why does this happen?

Obesity. NAFLD occurs most often because of excess weight. Normally, unused calories are stored in fat cells or adipose tissue. But there’s a limit to how much fat cells can expand. As fat cells reach their storage capacity, fatty acids leak into the bloodstream and travel to the liver. If overconsumption continues to exceed calorie burning, the liver can become overwhelmed as fat continues to build up.

Insulin resistance and type 2 diabetes. Insulin resistance occurs when cells respond poorly to insulin, leading to a buildup of glucose in the blood. To overcome resistance and lower blood sugar, the body tries to produce more insulin. However, higher insulin levels cause the liver to store unused glucose as triglycerides and stop the body from breaking down fat.

Inflammation. Fat, especially abdominal fat, is a metabolically active organ. Besides storing unused calories, abdominal fat also produces pro-inflammatory cytokines. In the liver, cytokines cause profound changes in hepatic protein metabolism, accelerating liver breakdown and damage.

High-cholesterol diet. Cholesterol isn’t just detrimental to your heart. At high levels, cholesterol can accumulate in the liver. It disrupts hepatic metabolism and damages liver cells by inducing inflammation. Moreover, some studies show that high cholesterol levels can also sabotage the liver’s self-healing ability.

Genes. Up to 39% of NAFLD cases are believed to have a genetic component. Among the genes linked with the NAFLD are the PNPLA3 and TM6SF2 genes. Mutations in these genes have been found to change the way the liver metabolizes and stores carbohydrates and fat.

Other risk factors include:

• Polycystic ovarian syndrome
• Pituitary gland dysfunction
• A diet high in simple carbohydrates
• Hypothyroidism
• Sleep apnea
• Gout

Stages and Key Symptoms of NAFLD

NAFLD is a broad spectrum of disease states with different manifestations that can affect each person differently. Some people may have features of multiple stages all at once. Some may progress more rapidly than others, while others may not worsen at all.

Stage 1: Simple fatty liver or Steatosis

At this stage, fat is just beginning to accumulate in the liver. But because the liver doesn’t have pain receptors, most people with steatosis don’t have symptoms. People who do have symptoms may experience intermittent nausea, fatigue, vomiting, and vague right-sided abdominal pain.

Steatosis is reversible with weight loss. Approximately 10-30% of people with steatosis will develop non-alcoholic steatohepatitis (NASH).

Stage 2: Non-Alcoholic Steatohepatitis

As fat accumulation progresses, liver cells eventually malfunction and die. This activates the inflammatory response, causing the liver to swell and press on adjacent organs. The swelling of the liver, also called hepatitis, may cause pain in some people.

At this stage, much of the liver is still functional and able to regenerate. However, between 5 and 12% of people with NASH develop fibrosis or permanent scarring within an average of 7 years if not treated. Those with obesity, type 2 diabetes, and genetic mutations are more likely to deteriorate faster.

Stage 3: Fibrosis

Over time, liver cells become too exhausted to repair the damage. Instead of producing new and healthy cells, the liver replaces the damaged cells with tough, fibrous tissue. Unlike healthy liver cells, fibrous tissue does not repair or perform any function. At this point, the liver damage is irreversible.

Stage 4: Cirrhosis

Eventually, widespread bands of scar tissue distort the internal structure of the liver, limiting both function and blood supply. The liver shrinks and becomes lumpy and cirrhotic. Cirrhosis occurs after many years of repeated or continuous injury.

Signs and symptoms of cirrhosis include:

• Jaundice
• Unexplained weight loss
• Swelling in the abdomen
• Fatigue
• Easy bleeding or bruising
• Itchy skin
• Foul-smelling, oily stools
• Clubbing of nails

NAFLD Screening and Diagnosis

NAFLD usually comes with no warning signs. This is why it is important to undergo regular screening, especially if you have one or more risk factors. Screening typically involves simple and non-invasive medical procedures.

Your doctor may run liver function tests to look for enzymes that might indicate NAFLD. However, liver enzymes can be unreliable and may not always be elevated in people with NAFLD or NASH. A handy alternative is an abdominal ultrasound, which is widely used to screen for steatosis.

If your liver enzymes are on the higher side, your doctor may retest after 6 months. If they’re still elevated and your liver appears to contain over 5% fat on ultrasound, you may undergo some additional tests, including:

• Medication and lifestyle review
• Hepatitis B screening
• Autoimmune antibodies test
• Fasting ferritin test
• Fibrosis risk scoring
• Repeat liver function
• Repeat ultrasonography

These tests are mostly used to rule out other conditions. Liver biopsy is still the gold standard and the only reliable way to diagnose and monitor NAFLD or NASH progression. It is also the only way to determine the stage or severity of fibrosis.

Despite current guidelines, liver biopsies are not routinely performed. In Canada, safer, less expensive imaging studies, like abdominal ultrasonography, are preferred.

How to Manage NAFLD

Your best bet at managing or even reversing NAFLD is to actively eliminate your risk factors. With the right plan in place, you can reduce your risk of complications and live a long, healthy life.

1. Shed Excess Pounds

The single best thing you can do to reverse NAFLD is losing weight. Studies show that losing 5-10% of your weight can:

• Improve your metabolic profile
• Reduce liver inflammation
• Decrease the amount of fat in your liver
• Fight insulin resistance
• Reduce cholesterol levels
• Enhance your overall health and mood

Approach weight loss by setting small, realistic goals for yourself. For example, a healthy weight loss target is 1 to 2 pounds per week. Losing weight too fast may actually worsen fatty liver.

To lose 1 to 2 pounds per week, you will need to be in a deficit of 3,500 calories. To do this, reduce your daily caloric intake by 500. Another option is to burn 500 calories through at least 30 minutes of daily moderate aerobic exercise.

A combination of caloric reduction, healthy eating, strength training, and exercise is critical for overall fat reduction.

2. Pharmacologic Measures

There are no specific drugs that can treat NAFLD. This may change soon as experimental drugs like FXR agonists go through clinical trials. For now, here are your potential drug options:

• Pioglitazone. Pioglitazone (Actos) is approved for the treatment of diabetes. Some studies show that pioglitazone also significantly reduces steatosis and liver inflammation in people with type 2 diabetes. It modulates the genes involved in glucose and fat metabolism in the liver and muscles.
• Vitamin E. Vitamin E is an antioxidant that has shown promise in improving liver inflammation. In Canada, vitamin E is only given to those with biopsy-confirmed NAFLD or NASH. Moreover, vitamin E may not be safe for people with diabetes and heart disease.
• Semaglutide. Semaglutide (Ozempic, Wegovy) has been approved for the treatment of type 2 diabetes. Used off-label for weight loss, it has also shown promise in reducing steatosis and liver inflammation in early trials. However, it is not yet used routinely for NAFLD.
• Statins. Your doctor may prescribe a statin (Atorvastatin) to get your cholesterol levels under control. Statins work by blocking the absorption and production of cholesterol. They can reduce your chances of dying from heart disease, which is surprisingly the leading cause of death in people with NAFLD. Moreover, studies suggest that statins may stop NAFLD from progressing to NASH.

3. Optimize Your Diet

Along with regular physical activity, a healthy diet is a cornerstone of NAFLD management. Here are some quick tips:

• Mind your portion sizes and eat only the amount of calories you need to stay healthy. Your doctor may refer you to a registered dietitian who can help you come up with a good target.
• Say no to foods high in saturated fats. These include red and fatty meats, dairy, canned meats, baked goods, and processed snacks. Instead, replace them with healthy fat from fish, avocados, yogurt, olive oil, seeds, and nuts.
• Bake, broil, boil, grill, or steam your food.
• Choose high-fiber nutrient-dense foods like green, leafy vegetables, whole fruits, whole grains, and legumes.

4. Take It Easy on Your Liver

When you have NAFLD or NASH, it is important to go easy on things that make your liver work harder. For example, you may need to stop drinking alcohol or limit your portions. Or, if you take acetaminophen for chronic pain, you may have to work with your doctor to find a safer option. Other liver-toxic drugs include rifampicin, anabolic steroids, chlorpromazine, and tamoxifen.

Precision Medicine: NAFLD Management Tailored to Your Genes

Precision medicine is an innovative approach to understanding and managing NAFLD on a genetic level. At SRx, we offer cutting-edge genomic solutions like nutrigenomics and pharmacogenomics that help you understand how your body works. Together, nutrigenomics and pharmacogenomics testing reveals a comprehensive view of your unique genetic makeup and can provide:

Early Screening and Targeted Intervention

With nutrigenomics testing, your genetic risk for NAFLD can be proactively identified. This allows you and your doctor to work together to create a preventative care plan as early in the disease course as possible.

Personalized Nutrition

Everyone has different nutritional needs. Nutrigenomics testing can shed light on the genetic variants that determine how different nutrients affect your liver. Your test results can help your nutritionist create a personalized diet plan.

For example, if you have a mutation in the PNPLA3 gene, you may benefit from:

• Reducing carb intake
• Upping omega-3 fats
• Supplementing with vitamin B
• Eating more fermented foods.

Personalized Drug Regimen

Pharmacogenomics testing looks for genetic variants that might affect your response to different drugs. Your pharmacogenomics information can:

• Help design a personalized treatment plan
• Reduce adverse effects
• Improve outcomes
• Reduce healthcare costs

For example, mutations in the CYP4F2 enzyme may affect vitamin E efficacy. Meanwhile, some variants of the PNPLA3 gene may reduce the efficacy of statins.

At SRx, we continuously strive to give our patients the tools to take proactive steps toward better health. Book a free consultation with our team to learn more about our services.