Introduction to Nonalcoholic Fatty Liver Disease
Muhammad Usman Naeem, Abdul Ghani MD
Why worry about Fatty Liver?
At present, nonalcoholic fatty liver disease ranks as the 2nd most common cause of chronic liver disease among patients waiting for liver transplants in the US [1]. As the prevalence of fatty liver rises, the rates of mortality and morbidity due to disease progression and complications such as liver failure, and cirrhosis will rapidly increase. According to a report published in the New England Journal of Medicine, by the year 2030, around 50% of adults in the US are expected to be obese, with 25% anticipated to develop severe obesity [2]. With an increase in obesity, there is going to be an increase in fatty liver. Timely detection and prevention of fatty liver is essential to reduce mortality rates for patients.
Who is at risk?
- Patients with low physical activity and consuming an unhealthy diet, which is high in salt, fat, sugar, and low in vegetables, are associated with a high prevalence of fatty liver.
- Patients with Type 2 diabetes mellitus (T2DM) are at high risk for developing fatty liver. More than 50% of T2D patients develop fatty liver, and the number is even higher for those with uncontrolled T2DM [3].
- Obese patients with visceral or abdominal adiposity are a major risk factor for fatty liver. It is also important to note here that normal weight doesn’t reduce the risk of fibrosis progression or development of fatty liver, but a weight increase of 4-5 pounds can increase the risk.
- Patients with metabolic syndrome, which includes dyslipidemia and hypertension, are also at higher risk for developing fatty liver. Moreover, the risk of developing hepatocellular carcinoma (CC) or cirrhosis also increases with each additional metabolic syndrome factor.
Screening
The most common screening blood tests for fatty liver are serum aminotransferases (alanine amino-transferase [ALT]) and aspartate aminotransferase [AST]). Both these tests are part of the comprehensive metabolic panel (CMP), which also includes other components of the blood to assess kidney, blood sugar, hypertension, and proteins. Every patient should get a CMP every 6 months to know their numbers. Remember that diabetes mellitus, fatty liver, high cholesterol, and hypertension are all number diseases. Understanding these numbers significantly increases your chances of preventing the disease or slowing its progression. For example, Elevated levels of ALT or AST may indicate fatty liver, typically showing ALT levels higher than AST. In addition to this pattern, gamma-glutamyltransferase (GGT) may also be elevated. However, serum aminotansferases may not be the most sensitive blood test for fatty liver. Some patients with fatty liver have normal AST and ALT levels. Normal AST and ALT tests do not rule out fatty liver but elevated test results with metabolic risk factors such as hypertension, diabetes, obesity, and high cholesterol are a common indication of fatty liver. Some of the other factors to keep in mind are the patient’s medication history, drug use, alcohol consumption, sexual history, occupational exposure, and family history of liver diseases such as Wilson’s disease.
If the blood tests are elevated, an ultrasound of the liver should be done, followed by noninvasive testing for fibrosis to diagnose fatty liver.Prevention and treatment
Diet
Nutrition is unequivocally the most important component to ameliorate and prevent fatty liver. Unfortunately, the average American diet consists of high amounts of high-fructose corn syrup (HFCS), processed meats, high glycemic index (GI) carbohydrates (CHO) and low in polyunsaturated fatty acids (PUFA). It is very important for patients to understand the components of their diet so they can elucidate what is beneficial for them.
1- Carbohydrate:
Carbohydrates are classified as simple or complex based on their chemical structure. There are also whole vs refined carbohydrates found commonly in the market.
Simple carbohydrates include glucose, fructose, galactose (monosaccharides), and sucrose, lactose, maltose, and cellobiose (disaccharides). Simple carbohydrates provide short-lasting burst of energy as they are quickly digested. Refined carbohydrate add calories but doesn’t provide micronutrients as they are processed to remove fiber-rich, protein, and fat-rich germ. Refined sugars can be found in sugary drinks, bread, white rice, sweets, and cereals.
Simple carbohydrates can be found naturally in nutritious foods like dairy and fruits. As unprocessed carbohydrates, they provide fiber, minerals, and vitamins. Different foods can be categorized according to their GI, which shows how quickly and the extent to which that food can lead to rises in blood sugar levels.
Complex carbohydrates are digested more slowly and thus often make individuals feel full longer. Some examples of complex carbohydrates include whole grain, starchy vegetables, and fiber. Patients with high consumption of carbohydrates develop significant increases in serum triglyceride (TG) levels and hepatic steatosis.
2- High-Fructose Corn Syrup (HFCS)
High Fructose Corn Syrup (HFCS) is commonly used as a sweetening agent and to retain moisture in cookies, which is beneficial for the baking industry as American corn is inexpensive. Corn syrup is cheaper than table sugar and is often found in cookies, soft drinks, and fruit juices. While fructose is related to glucose, when absorbed in the stomach and processed in the liver, fructose can be converted into fat, which damages liver health. Avoid Fructose, stop consuming baked goods like cookies. Cookies provide empty calories without nutritional value. Instead, eat fresh fruits and drink freshly squeezed orange juice.3- Fats
When considering fatty liver, it’s important to think about the types of fat in the diet. As mentioned in the fat chapter, different fats can affect liver health and body fat differently, even if there is no overall weight gain. Trans fat (bad fat example cheese and red meat) not only damages liver but also makes it harder to lose weight. Omega-3 fats are better to consume compared to omega-6 fats when it comes to preventing fat buildup in the liver. Additionally, omega-6 is pro-inflammatory, while omega-3 is anti-inflammatory. Diets high in omega-3 also seem to improve how well the body uses insulin.
High triglycerides (more than 500 mg/dL) are a common indication of fatty liver, which is confirmed by a liver ultrasound. 5-10% of fatty liver develops into cirrhosis and then liver failure.
4- Eat more vegetables
Eating more vegetables is essential for maintaining a healthy gut. These bacteria are harmless inside the gut and harmful outside the gut. The beneficial bacteria create a protective lining in the intestines, allowing them to flourish in their natural environment. When we eat less vegetables, the bacteria made lining is not good and they leak into the blood and go to the liver. Leaked bacteria in the liver can cause inflammation and transform fatty liver into scar tissue. Moreover, alcohol and fructose can also damage the intestinal lining and contribute to leaky gut.
5- Ozempification of the Liver
GLP-1 receptor agonists (Ozempic and Trulicity) have been miracle drugs. Although the pool of patients who are eligible to receive Ozempic is small (only type 2 diabetic patients), it can also prevent or slow the progression of various diseases, including fatty liver. It is simple to reduce fatty liver, we first need to lose the belly fat. This is where GLP-1 jumps in. GLP-1 is a gastrointestinal peptide (protein in the gut) that aids insulin release when blood sugar levels rise. It also lowers the release of glucagon, a hormone that raises blood sugar, and slows down how quickly the stomach empties [4]. This improves glycemia, promotes appetite suppression and satiety, which can lead to weight loss. Moreover, GLP-1 receptor agonists also lower the liver’s production of new fats (de novo lipogenesis) and reduce levels of free fatty acids, which are linked to triglyceride-derived toxic metabolites (harmful fat in the body) [5].
Citation list
- Bu, T., Sun, Z., Pan, Y., Deng, X., & Yuan, G. (2024). Glucagon-like peptide-1: New regulator in lipid metabolism. Diabetes & Metabolism Journal, 48(3), 354–372. https://doi.org/10.4093/dmj.2023.0277
- Müller, T. D., Finan, B., Bloom, S. R., D’Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., Holst, J. J., Langhans, W., Meier, J. J., Nauck, M. A., Perez-Tilve, D., Pocai, A., Reimann, F., Sandoval, D. A., Schwartz, T. W., … Tschöp, M. H. (2019). Glucagon-like peptide 1 (GLP-1). Molecular Metabolism, 30, 72–130. https://doi.org/10.1016/j.molmet.2019.09.010
- Kanwal, S., Ghaffar, T., Aamir, A. H., & Usman, K. (2021). Frequency of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus and its associated risk factors. Pakistan Journal of Medical Sciences, 37(5). https://doi.org/10.12669/pjms.37.5.4211
- Ward, Z. J., Bleich, S. N., Cradock, A. L., Barrett, J. L., Giles, C. M., Flax, C., Long, M. W., & Gortmaker, S. L. (2019). Projected U.S. state-level prevalence of adult obesity and severe obesity. New England Journal of Medicine, 381(25), 2440–2450. https://doi.org/10.1056/nejmsa1909301
- Pais, R., Barritt, A. S., Calmus, Y., Scatton, O., Runge, T., Lebray, P., Poynard, T., Ratziu, V., & Conti, F. (2016). NAFLD and liver transplantation: Current burden and expected challenges. Journal of Hepatology, 65(6), 1245–1257. https://doi.org/10.1016/j.jhep.2016.07.033
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