Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent adverse health condition that poses severe health risks and creates a significant economic burden on the healthcare system. The situation around NAFLD is worsened by the fact that reliable NAFLD diagnostics require a liver biopsy, an invasive and expensive procedure rarely performed compared to standard radiological scanning. As a result, people from high-risk population groups may develop NAFLD without knowing about their dangerous health condition. Given this situation, one can see a need for a reliable preventative solution that may reduce the risk of NAFLD development. This research paper discusses the issues in NAFLD diagnostics and the physiological and economic effects of NAFLD and makes a case for increased choline intake as a promising solution to the NAFLD problem. In particular, the review of scholarly sources points to choline’s effectiveness in fat accumulation reduction, which is useful for eliminating the strongest NAFLD risk factors.
Non-alcoholic fatty liver disease (NAFLD) is the focus of this research paper. The research questions discussed in this paper are the NAFLD diagnostic procedures, physiological aspects of NAFLD, the economic effects of this condition, and the use of choline as a preventative supplement. The disorder known as NAFLD causes an accumulation of extra fat in the liver (Pouwels et al., 2022). Heavy drinking does not contribute to this fat accumulation, unlike in most cases of liver disease. Most people get one type of NAFLD or the other, while occasionally, those with one form are later found to have the other type. For NAFLD, healthcare professionals stipulate that the demographics at risk entail people with high triglycerides, high cholesterol, and those who are obese or overweight. Furthermore, people with bad eating habits and those experiencing rapid weight loss remain susceptible to the disease (American Liver Foundation, 2022). NAFLD affects a massive population in the United States due to its stealthiness and the high incidence and prevalence rate; hence the need for an unconventional solution is evident.
The interest in the topic arises from the comprehension that NAFLD occurs quietly without any apparent symptoms until a blood test happens. In some instances, the abnormal blood results from the liver function test can lead to a misdiagnosis. In a worst-case scenario, the affected individual would reach a life-threatening stage before realizing it was NAFLD. What makes it worse is that there is no direct medical treatment in the face of the ever-rising rates of high cholesterol, diabetes, and obesity cases. A liver transplant is the most feasible solution upfront in a healthcare setting, especially given NAFLD is the reason for most liver transplants (Alswat et al., 2019). Unfortunately, with the disease seeping into the population gradually, even liver donors seem to be at some stage of NAFLD, unbeknownst to them.
The paper consists of four major parts related to the topics in the research focus. The first part provides an overview of the current situation with NAFLD diagnostic methods. The second part describes the extent of economic issues created by NAFLD. The third part explores NAFLD’s clinical picture, covering such aspects as disease pathogenesis, prevalence, and harmful biological changes provoked by NAFLD. Finally, a special section is dedicated to the potential use of choline as an essential supplement for NAFLD prevention and management. In this regard, the paper attempts to create a comprehensive overview of NAFLD and propose a solution for disease management in at-risk populations and patients already diagnosed with NAFLD.
NAFLD diagnostics is a challenging process since this disease is resistant to early detection. According to Huang et al. (2020), early NAFLD diagnosis depends on a timely identification of hepatic steatosis (HS) that may point to the development of non-alcoholic steatohepatitis (NASH). However, noninvasive hepatic steatosis may be misleading and yield inaccurate results. For instance, the serum markers of liver function can be elevated in NASH cases but not necessarily point to the development of advanced liver disease, such as NAFLD (Huang et al., 2020). Most NAFLD diagnoses in clinical practice are made via radiological scanning. Whereas this diagnostic technique is more comfortable for the patients, the results are less reliable in patients with intermediate and significant disease severity (Huang et al., 2020). In this regard, an invasive liver biopsy procedure offers the best chance for early detection of NAFLD. However, a biopsy may produce such complications as pain, bleeding, sepsis, and injury to surrounding organs (Huang et al., 2020). As a result, physicians resort to biopsy only when non-invasive radiological methods do not offer undeniable evidence of NAFLD.
In the United States case, the American Association for the Study of Liver Diseases offers detailed guidance for NAFLD diagnostics. Firstly, the Association advises against routine screening for NAFLD in high-risk groups and family members due to uncertainties surrounding diagnostics tests and inconsistent heritability, respectively (Chalasani et al., 2018). However, the patients diagnosed with type 2 diabetes are recommended for screening as a specific group with a high NAFLD suspicion index (Chalasani et al., 2018). Secondly, the guidance sets four clear conditions for a NAFLD diagnosis. In particular, a patient must have confirmed HS, the patient’s alcohol consumption should be insignificant, and the competing etiologies and causes of HS and chronic liver disease (CLD) must not exist (Chalasani et al., 2018). As an expensive, invasive, and demanding procedure from the professional perspective, liver biopsy is recommended only in complicated cases when radiology is insufficient for excluding other HS and CLD etiologies (Chalasani et al., 2018). Overall, one can see that NAFLD poses a significant challenge in terms of non-invasive and effective early detection. A NAFLD case may remain undetected without a liver biopsy, and a liver biopsy can only be conducted under specific circumstances.
NAFLD: The Economic Perspective
NAFLD development is a complicated process anatomically and physiologically that is still not fully understood. The pathogenesis of NAFLD and related illnesses has been the subject of much animal study in recent years, mostly to compare the effects of various dietary models on the development of this condition (Pouwels et al., 2022). It has been proposed that the development of the NASH is a two-step process based on the current findings of the research studies. This process begins with the liver accumulating fat, which makes insulin resistance worse (Pouwels et al., 2022). Thus, NAFLD’s pathogenesis is linked to fat accumulation in the liver and the subsequent development of insulin resistance.
The economic issues involved in understanding NAFLD’s impact on the population are the cost burden that this condition places on the healthcare system. This disease is linked to metabolic symptoms and obesity, and therefore, the researcher can focus on examining some issues outside of health-related linked to this disease. In the research by Shetty and Syn (2019), the authors examined the economic burdens that patients with this condition experience. Due to the significant clinical burden and anticipated growth in the number of patients who have NAFLD over the following ten years, this condition is anticipated to have an exponential effect on the financial burden. A survey of Medicare beneficiaries with NAFLD hospitalized in 2010 found that the median annual total payment was approximately $11,000 per individual (Shetty & Syn, 2019). Thus, NAFLD is an economic concern for the government providing Medicare services and the patients receiving care.
However, one should compare the economic impact of NAFLD on patients as opposed to the payments that individuals with other conditions have to make. The study found that Medicare advantage plan holders with NAFLD had annual median outpatient care costs of $5,363, which was significantly higher than the $4,111 for the control group (Shetty & Syn, 2019). These costs were compared between patients with NAFLD and a control group with similar metabolic comorbidities. The yearly state’s economic burden is projected to increase to $103 billion from just direct medical care expenditures and to $188 billion from societal costs associated with NAFLD (Shetty & Syn, 2019). Thus, NAFLD is a serious economic concern for the population and policymakers.
The economic approach related to this issue is the question of the economic burden that patients with chronic conditions experience due to the need to receive routine medical care. As was discussed previously, Shetty and Syn (2019) report a higher amount of Medicare payments associated with this disease as opposed to other conditions. Statistical factors related to this issue also raise concerns due to the high prevalence of NAFLD. According to Pouwel et al. (2022), “NAFLD is the most common chronic liver disease in the Western world” (p. 10). Moreover, the same authors report that 30% of the United States population have this condition; NAFLD is more prevalent in people with specific diseases and conditions, including obesity and ailments like type 2 diabetes that may be connected to obesity. According to studies, one-third to two-thirds of persons with type 2 diabetes are thought to have NAFLD. NAFLD is also thought to affect up to 75% of overweight adults and more than 90% of people with extreme obesity (Pouwels et al., 2022). Therefore, apart from caring for NAFLD, many patients also have to spend money on other chronic conditions they have.
Physiological Perspective of NAFLD
The physiological perspective explores such spheres as NAFLD pathogenesis, prevalence, risk factors, and potential solutions for disease management. NAFLD encompasses conditions ranging from simple steatosis and NASH to the eventual permanent damage of cirrhosis (Sherriff et al., 2016). It becomes even more interesting when there is credence to the fact that it is the most common liver disorder in the US and affects about a quarter of the adult population (Salinas, 2016). Thus, this paper proposes a novel approach to using choline supplements to combat the risk of developing fatty liver disease. The purpose of the paper lies in showing how ineffective conventional techniques have been to the masses and how the idea of choline supplements might be the key to mitigating NAFLD.
The second stage of this process involves cellular and molecular alterations brought on by oxidative stress and the oxidation of fatty acids in the liver. This process is a result of numerous factors, including “cytokine injury, hyperinsulinemia, hepatic iron or lipid peroxidation, variation in the extracellular matrix, altered energy homeostasis, and altered immune system function (Pouwels et al., 2022, p. 10). It takes a complex procedure for insulin resistance to develop. Increased fat mass and adipocyte differentiation are crucial factors in the emergence of insulin resistance in the context of this condition.
From the epidemiological perspective, NAFLD has affected a large portion of the global population. According to Cotter and Rinella (2020), 25% of the global population has NAFLD, and in the United States, 30% of the population is affected. Therefore, NAFLD is a serious health concern for the global healthcare community, which requires attention to better understand its causes and effects on the wider population.
As with any other disease, NAFLD impacts the body systems of an individual. The liver is the main body system affected by NAFLD (Cotter & Rinella, 2020). The liver receives all the blood that exits the intestines and stomach. This blood is processed by the liver, which also breaks down, balances, and produces nutrients (Cotter & Rinella, 2020). It also metabolizes medications to make them more easily absorbed by the body or nontoxic. Thus, the liver is an essential body system, and NAFLD impairs the ability of this organ to function.
Certain changes causing the development of NAFLD occur at the cellular level. There have been several attempts to examine these interactions in vitro and in vivo due to the significance of cell-cell interactions for every aspect of NASH. Co-culturing cells with traditional 2D techniques or in 3D spheroids enable functional characterization of these interactions but are limited by the poor replication of the environment that governs NASH in vivo (Wallace et al., 2022). Investigations frequently focused on two subpopulations rather than the multicellular environment. These culture systems also lack flow conditions, making it difficult to understand extrahepatic mediators, such as dietary supplements or microbial-associated molecular patterns from the gut, adipose tissue mediators, as well as patrolling immune cells (Wallace et al., 2022). Therefore, there have been studies examining the development of NAFLD at the cellular level, which help understand this condition better.
From the viewpoint of biological issues, NAFLD raises the question of the biological factors that impact the development of this condition. According to studies by Pouwel et al. (2022), Wallace et al. (2022), and Mazzoccoli et al. (2018), biologically, the predisposition to this condition is linked to obesity, diabetes, or insulin resistance. Therefore, this condition is a comorbidity of other chronic illnesses that affect the functioning of one’s body.
The current means of identifying patients who suffer from NAFLD lies in conducting a liver test function which may yield mixed results. The confirmation of excess fats in the liver has led to the introduction of invasive and noninvasive methods. Blood tests and imaging using, say, screening and transient elastography comprise noninvasive tests that can predict the presence of NAFLD and remain limited in eliminating all doubt (Alswat et al., 2019). For NASH, the mildly aggressive form of NAFLD that entails liver inflammation and damage to a considerable extent, it requires a liver biopsy. This invasive form of diagnosis assesses the progression of fibrosis to rule out other liver disorder causes and any doubts (Alswat et al., 2019). The stage at which it is possible to mitigate NAFLD’s adverse effects depends on championing prevention measures such as healthy lifestyles. However, recent research also points to the possibility of genetic predisposition to NAFLD (Juanola et al., 2021). Considering the devious nature of NAFLD, this paper aims to propose an outside-the-box solution to gain the momentum, necessary for disease prevention and management.
The Choline Theory
Choline metabolism occurs in the liver allowing the breakdown of lipids into energy. With more breakdown of lipids, choline counters the risk of developing NAFLD as the supplements provide the body with the necessary minerals and vitamins for the liver to function at its optimum. This proposal accomplishes the task of minimizing the risk to vulnerable demographics whose livers could fail due to low choline intake, genetics, age, gender, and estrogen levels. The intended goal is to further the theory that choline supplements could be vital in nullifying the NAFLD threat. Individuals with the disease lack adequate choline levels to maintain optimum liver functionality. When NAFLD patients got prescribed choline supplements in addition to doses of coenzyme Q10, polyunsaturated omega-3-series’ fatty acids, vitamin D, vitamin E, and silymarin in the proper parameters. As a result, the NAFLD adverse effects were significantly alleviated (Cicero et al., 2018). Therefore, there is a realistic chance that choline supplements could be the next best thing, especially for at-risk demographics.
Several scholarly sources confirmed the negative influence of choline deficiency on liver health conditions. According to Mazidi et al. (2018), a choline-deficient diet with a daily choline intake lower than 50 mg may lead to fat accumulation in the liver in a few days to a few weeks. As such, one can see that choline is necessary for normal liver functioning. Nutritional recommendations highlight choline’s usefulness as a therapeutic tool for NAFLD prevention and management (Radziejewska et al., 2019). Choline supplementation is paramount for general liver health preservation since choline stores in the human organism become depleted after three weeks of insufficient intake, creating the possibility of liver dysfunction development (Radziejewska et al., 2019). Supplementation may also be advised due to the fact that bacteria in the human gastrointestinal tract utilize choline, leaving a lower share for absorption (Goh et al., 2021). Consequently, one has to include choline-rich products, such as dairy, nuts, beef, and leafy greens into their diet, or compensate for the insufficient choline intake with special food supplements.
Two large-scale studies confirmed the epidemiological connection between choline consumption and the risk of NAFLD development. Yu et al. (2014) studied 56,195 Chinese men and women and found that a higher choline intake was associated with a lower NAFLD risk (as cited in Mazidi et al., 2019, p. 2). The positive impact of increased choline intake was consistent after adjustment for additional factors, such as lifestyle, sociodemographic characteristics, and dietary intakes (Mazidi et al., 2019). Furthermore, Mazidi et al. (2019) studied 20,643 US adults and found a positive association between higher choline consumption and fatty liver index (FLI) reduction. For instance, an increase in choline intake from 272 mg/d to 356 mg/d resulted in FLI reduction regardless of the body mass index (BMI). In particular, the FLI decreased from 79.3 to 74.1 in the low BMI category and from 32.1 to 20.6 in the high BMI category (Mazidi et al., 2019). Given these findings, one can claim that choline supplementation can be considered a promising way of NAFLD prevention and management.
An overabundance of excess fat builds up in the liver as a result of NAFLD. Unlike other situations, heavy drinking does not cause this fat to accumulate. The term “alcohol-associated liver disease” refers to a condition where excessive alcohol consumption causes liver fat to build up. Functional evaluation of the cellular effect of NAFLD is made possible by co-culturing cells using conventional 2D methods or in 3D spheroids. However, this method is constrained by the inadequate in vitro replication of the environment that controls NASH.
Additionally, the lack of flow conditions in these culture systems makes it challenging to comprehend extrahepatic mediators. It is estimated that only the cost of providing direct medical care will add $103 billion to the US economy per year. In the Western world, NAFLD is the most prevalent chronic liver disease, affecting approximately 25% of the population.
The situation around NAFLD prevalence is worsened by the complexity and relatively low reliability of contemporary diagnostics procedures. The most accurate disease diagnostic requires an invasive and expensive liver biopsy procedure, while the common radiological scanning is not universally successful at excluding HS and CLD etiologies. Consequently, NAFLD is highly resistant to early detection, which leaves prevention as the best option for countering this disease.
Therefore, the continued uptake in NAFLD diagnoses is not a trend that will slow down, given the continued increase in nations joining developed countries where the disease is prevalent. It is a disease that has proven impossible to treat and hard to diagnose or prevent, affecting many in its wake. Given the known information about the ailment, the multitude of challenges in detecting its presence to begin mitigation has proven difficult. With no cure for the disease available, it becomes necessary to adopt solutions beyond the norm, such as introducing choline supplements. It takes into effect that the best way to counter NAFLD at this moment is prevention which the supplements achieve sufficiently.
In this respect, choline can strengthen the liver’s ability to break down lipids into energy, thus reducing the chance of fat accumulation. The insights from the scholarly sources suggest that choline supplementation can reduce FLI in various population groups, regardless of age, gender, and lifestyle. Consequently, choline may play a vital role in NAFLD prevention efforts due to its effectiveness in liver fat accumulation reduction. Given the fact that increased liver fat level is directly associated with the risk of NAFLD development, choline supplementation can be considered a promising option for NAFLD prevention and management.
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