Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of American adults. Since 2011, studies have found that the number of cases of clinically significant liver fibrosis have more than doubled!² NAFLD is likely underdiagnosed as there are typically no symptoms.  It may take years for symptoms to develop. It is prudent to spread awareness due to increasing prevalence, underdiagnosis, and worsening outcomes. The good news: non-alcoholic fatty liver disease is preventable! It can also be managed to prevent progression and in some cases may even be reversed!!

Let’s start from the beginning: “What is Fatty Liver Disease?”. Like the name eludes, there is excess fat in your liver. This eventually results in liver impairment and body system dysfunction. There are two main categories: 1) non-alcoholic fatty liver disease (NAFLD) and 2) alcoholic fatty liver disease. I am going to focus on NAFLD, which occurs when no or little alcohol is consumed. Once there are signs of inflammation and liver cell damage this is referred to as non-alcoholic steatohepatitis (NASH). If not properly managed this can lead to fibrosis and cirrhosis (permanent scarring of the liver), resulting in severe liver dysfunction and increased risk of liver cancer.

The liver is an important organ as it helps with digestion, metabolism, and elimination of toxins. In liver disease you may experience digestion issues, mental status changes, cardiovascular disease, bleeding, fluid retention, and more. Ultimately, severe liver disease leads to multiorgan dysfunction and failure with a high mortality rate. I will discuss risk factors, prevention, diagnosis, and treatment of NAFLD.

Risk Factors

• Prediabetes OR Type II Diabetes
• Being overweight
• High cholesterol and/or triglycerides
• High blood pressure
• Certain medications (i.e. steroids, amiodarone, tamoxifen)
• Metabolic syndrome (check out my post https://lrxwellness.com/a-silent-killer/)
• Some infections (i.e. hepatitis C)
• Hypothyroidism
• Hormone deficiencies
• Polycystic ovarian syndrome (PCOS)
• Tobacco use
• Obstructive sleep apnea- while this is more of an association, it is believed that apneic periods may lead to mitochondrial dysfunction, impaired glucose and fat metabolism, increased insulin resistance, and fat production in the liver².

Prevention

1. Diet– Incorporate those essential macro and micronutrients. Check out the nutrition section of this post https://lrxwellness.com/a-paradigm-shift/. Reduce saturated fats, refined carbs, and sugar. Evidence supports the Mediterranean diet (i.e. fruits, vegetables, legumes, nuts, lean meats). Interestingly, coffee consumption may reduce the risk of NAFLD².
2. Exercise– Check out my post on exercising effectively https://lrxwellness.com/how-to-exercise-effectively/
3. Management of existing metabolic conditions (as listed above)
4. Gut health– animal studies have confirmed that gut microbiome plays a role in NAFLD development³. Examples of foods that improve gut microbiome include: nuts, legumes, fruits, vegetables, whole grains, and dairy.

Diagnosis

NAFLD or NASH is often an incidental finding, meaning without symptoms it is picked up during other workup. For example, during routine bloodwork it may be found that liver function tests (AST, ALT) are abnormal. Or upon abdominal imaging (such as ultrasound, CT scan, or MRI) a fatty liver is noted. It is important to note that an abdominal ultrasound is less specific in the setting of obesity. A study found that NASH was identified in 14% of asymptomatic patients undergoing colon cancer screening¹. All that being said, the gold standard for NASH diagnosis is a liver biopsy. However, considering it’s limitations it is not often used in practice. Vibration controlled transient elastography (VCTE) is an ultrasound method that is objective and more sensitive compared to a standard ultrasound. MRI-PDFF is the most sensitive method (next to liver biopsy) but not routinely used due to cost. The most effective non-invasive tool to assess and predict fibrosis outcomes is the scoring system referred to as FIB-4. The score is calculated using age, liver function blood tests, and platelet count.

So who should be screened for fibrosis? The American Association for the Study of Liver Disease (AASLD) recommends screening in high risk populations such as: type 2 diabetes, obese with metabolic complications, family history, and/or significant alcohol use. Identifying and treating individuals who are asymptomatic with early fibrosis has the potential to improve quality of life and prevent future negative outcomes.²

Treatment

1. Diet– reduce saturated fats, refined carbs, and sugar.
2. Exercise– the consensus is exercise as much as you can. Studies have found more exercise = more liver fat loss.
3. Weight loss- >10% weight loss has the most significant impact on outcomes.
4. Management of comorbidities (i.e. diabetes, high cholesterol, etc)
   • Medications: GLP1 agonists (semaglutide, liraglutide) and SGLT2 inhibitors (empagliflozin, dapagliflozin) used to treat diabetes have been found to improve liver steatosis.
5. Medication discontinuation when indicated
6. Limit alcohol consumption

In Conclusion

Non-alcoholic fatty liver disease is often a silent disease, meaning there are no symptoms. It is estimated that approximately 25% of American adults have NAFLD. There is an increasing prevalence likely in part due to soaring rates of metabolic disease and syndrome. Raising awareness is prudent in preventing adverse health outcomes and improving overall health of our population. NAFLD is preventable, manageable, and even reversible in some cases!

Please reach out with questions, comments, or for further discussion.

Lindsey, PharmD, BCPS

References:

Harrison, S. A., Gawrieh, S., Roberts, K.,et al. (2021). Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged us cohort. Journal of Hepatology, 75(2), 284–291. https://doi.org/10.1016/j.jhep.2021.02.034

Rinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023). Aasld Practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology, 77(5), 1797–1835. https://doi.org/10.1097/hep.0000000000000323

Romero-Gómez, M., Zelber-Sagi, S., Martín, F., Bugianesi, E., & Soria, B. (2023). Nutrition could prevent or promote non-alcoholic fatty liver disease: An opportunity for intervention. BMJ. https://doi.org/10.1136/bmj-2023-075179

U.S. Department of Health and Human Services. (2021, April). Nonalcoholic fatty liver disease (NAFLD) & Nash – NIDDK. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash