▎ WuXi AppTec content team editor
Non-alcoholic fatty liver disease (NAFLD, commonly known as fatty liver), a common liver disease, affects more than 25% of adults worldwide, and there are nearly 250 million existing fatty liver patients in China. Many people who have entered middle age or even very young may have received a "fatty liver warning" on the physical examination report.
Fatty liver includes a range of disease processes. Initially non-alcoholic simple hepatic steatosis (NAFL), if not treated in time, the accumulation of fat in the liver can lead to inflammation, can develop non-alcoholic steatohepatitis (NASH), gradually cause liver fibrosis, and eventually may develop into cirrhosis or even liver cancer, liver failure.
Fatty liver is also a risk factor for atherosclerotic cardiovascular disease, which is also the leading cause of death in patients with fatty liver disease.
If the relevant tests are not done, it is difficult to detect fatty liver, because the disease has no obvious symptoms, and by the time symptoms appear, it is likely to have developed to an advanced stage, causing irreversible damage to the liver. Therefore, identifying the risk factors of fatty liver and taking preventive measures will effectively prevent the occurrence and development of fatty liver.
Recently, the American Heart Association (AHA) published "Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association" (hereinafter referred to as the statement), Risk factors, hazards, detection methods and interventions for fatty liver are introduced. In today's content, we'll share some of the highlights from the statement.
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The prevalence of fatty liver in adults and children is increasing, with the global prevalence of fatty liver likely to exceed 35% over the next 10 years, the statement noted. Identifying risk factors for fatty liver disease and preventing the development of fatty liver disease is also an important part of the prevention and treatment of cardiovascular disease.
Risk factors
The statement pointed out that the risk factors for fatty liver mainly include lifestyle, metabolic or endocrine diseases, pharmaceutical factors and genetic factors.
1. Lifestyle
Lifestyle plays an important role in the occurrence and treatment of fatty liver. Dietary factors associated with hypertriglyceridemia, hyperglycemia (fasting and postprandial), insulin resistance, and risk of weight gain are also associated with an increased risk of fatty liver.
Increased carbohydrate intake, especially in the form of monosaccharides, can exacerbate hypertriglyceridemia and hyperglycemia in many patients, thereby increasing the risk of fatty liver disease. A high intake of fat in the diet may also lead to elevated triglyceride levels, increasing the risk of fatty liver disease.
Weight gain is a multifactorial disorder that not only directly increases the risk of fatty liver disease, but also exacerbates multiple risk factors for fatty liver, including increased triglyceride production, insulin resistance, hyperglycemia, and hypertriglyceridemia. It should be noted that although fatty liver disease mostly occurs in obese people, 10%-20% still occurs in people with healthy weight.
Lack of physical activity increases the risk of being overweight or obese, insulin resistance, and leading to fatty liver disease.
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2. Metabolic or endocrine diseases
Some metabolic or endocrine disorders, such as type 2 diabetes, insulin resistance, dyslipidemia, metabolic syndrome, dyslipidemia, dysphagia, chronic kidney disease, polycystic ovary syndrome, etc., are associated with an increased risk of fatty liver disease.
(1) Type 2 diabetes mellitus
Type 2 diabetes and impaired glucose tolerance are important risk factors for fatty liver and nonalcoholic steatohepatitis.
Type 2 diabetes is associated with insulin resistance, hyperglycemia, hypertriglyceridemia, increased free fatty acids from adipose tissue to the liver, and abdominal obesity, all of which are associated with an increased risk of fatty liver and nonalcoholic steatohepatitis.
(2) Dyslipidemia
Hypertriglyceridemia has been associated with insulin resistance, impaired glucose tolerance, type 2 diabetes, abdominal obesity, obesity, and metabolic syndrome, all of which have been linked to an increased risk of fatty liver.
(3) Metabolic syndrome
Metabolic syndrome is associated with insulin resistance, hyperglycemia, abdominal obesity, and hypertriglyceridemia, which may increase the risk of fatty liver disease. Metabolic syndrome is also associated with an increased risk of steatohepatitis and liver fibrosis.
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(4) Fat metabolism disorders
Fat metabolism disorder refers to the occurrence of obstacles in the production, utilization and storage of fat in the body, which can cause fat loss or fat accumulation.
Impaired fat metabolism is associated with insulin resistance and abnormal deposition of triglycerides, which may cause fat to accumulate in the liver, triggering fatty liver.
(5) Chronic kidney disease
In patients with non-alcoholic steatohepatitis, the prevalence of chronic kidney disease is higher. Both nonalcoholic steatohepatitis and chronic kidney disease have been linked to abdominal obesity, type 2 diabetes, metabolic syndrome, and insulin resistance.
Chronic kidney disease may also increase or exacerbate the risk of fatty liver disease by altering intestinal barrier function and microbiota composition, accumulation of toxic metabolites from uremia, and alteration of glucocorticoid receptor metabolism.
(6) Polycystic ovary syndrome
PCOS is characterized by chronic anovulation and hyperandrogenicemia and is strongly associated with obesity and insulin resistance, which are 2 key risk factors for nonalcoholic steatohepatitis.
Studies have shown that about 25% to 40% of patients with PCOS have non-alcoholic steatohepatitis; patients with PCOS have a 2.5-fold increased risk of fatty liver disease.
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3. Drug factors
Side effects of some drugs, such as alcohol, amiodarone, aspirin, corticosteroids, lometamidine, mipomethen, nonsteroidal anti-inflammatory drugs, reverse transcriptase inhibitors, tamoxifen, tetracycline, valproic acid, etc., may also increase the risk of fatty liver.
Therefore, when using these drugs, it is necessary to carefully read the instructions and use them under the guidance of medical staff to avoid adverse reactions and increase the risk of fatty liver.
4. Genetic factors
Genetic factors mainly refer to a family history of fatty liver and some genetic mutations.
Studies have shown that some people in the family have a fatty liver, and others have an increased risk of fatty liver disease. Some genetic mutations, such as carrying GCKR, MBOAT7, PNPLA3, TM6SF2, HSD17B13 and other mutations, also increase the risk of fatty liver disease.
In addition to the above risk factors, endothelial dysfunction, inflammation, abnormal fat deposition in other organs (e.g., pancreas, skeletal muscle, and epicardial membrane), hypo β-lipoproteinemia, lysosomal acid lipase deficiency, and defects in mitochondrial fatty acid oxidation (congenital and acquired) may also increase the risk of fatty liver.
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Interventions
The statement states that the main objectives of the intervention for fatty liver are:
Protect liver function and prevent the progression of disease to end-stage liver disease and hepatocellular carcinoma;
Prevention and treatment of metabolic complications such as diabetes mellitus, dyslipidemia and metabolic syndrome;
Prevention of cardiovascular complications.
However, fatty liver has not yet been approved for targeted drugs or surgeries, and key interventions are mainly lifestyle interventions, such as dietary interventions, alcohol withdrawal, increased physical activity, and weight control (weight loss of 5%-10%). Lifestyle interventions are also the cornerstone of lipoietic and nonalcoholic steatohepatitis interventions.
1. Dietary interventions
Dietary adjustments can help with weight loss and alleviate fatty liver processes. Some dietary recommendations, such as limiting calories, carbohydrates, and fat intake, drinking fewer sugary drinks, and not eating food before bedtime, can also reduce fat levels in liver cells.
The Mediterranean diet has been shown to reduce liver fat and improve insulin sensitivity. Currently, the Mediterranean diet is also a specific dietary model recommended by the European Association for the Study of Liver/European Association for the Study of Diabetes/European Obesity Research Association for the Treatment of Fatty Liver and Nonalcoholic Steatohepatitis Clinical Practice Guidelines.
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2. Avoid alcohol
Excessive alcohol consumption (> 2 times a day) is an independent risk factor for liver steatosis. Ethanol causes many metabolic changes in the liver, making liver cells susceptible to excess fatty acids and triglycerides, as well as reducing fatty acid β-oxidation and very low-density lipoprotein secretion.
Studies have shown that excessive alcohol consumption is associated with an increased risk of alcohol-related liver disease and cirrhosis. Moreover, in patients who have been diagnosed with non-alcoholic steatohepatitis, drinking alcohol promotes disease progression, so drink alcohol should be avoided altogether.
3. Physical activity
Physical activity is another necessary lifestyle intervention for fatty liver management that not only helps with weight loss, but also reduces liver steatosis, increases free fatty acid uptake in muscle cells, and increases insulin sensitivity.
4. Weight loss
In obese patients, weight loss of at least 10% is associated with 90% reduction in non-alcoholic steatohepatitis, decreased liver fibrosis, and improvement in inflammation in the portal area; small weight loss (e.g., 5%), is associated with about 40% of non-alcoholic steatohepatitis.
There are also studies that show that liver fat is reduced by at least 90% in 10% of patients who maintain weight loss ≥.
Overall, multiple studies have shown that weight loss of 10% or more by reducing energy intake and increasing energy expenditure can have a significant relief and reversal effect on fatty liver and non-alcoholic steatohepatitis.
For patients who cannot achieve weight loss through lifestyle changes alone, it is possible to take weight loss medications or undergo bariatric surgery if necessary to achieve weight loss, alleviate or reverse fatty liver.
In addition, the statement noted that some drugs, such as pioglitazone, liraglutide, smeglutide, metformin, lipid-lowering drugs (such as statins), leptin, vitamin E, farnidol X receptor agonists, etc., may have potential beneficial effects on fatty liver.
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brief summary
All in all, fatty liver is an increasingly common disease and is not easily detected.
In order to prevent the occurrence and development of fatty liver, we must not only recognize its risk factors, so as to take preventive measures; we should also regularly carry out relevant tests or physical examinations, such as imaging tests, etc., to timely detect liver steatosis, so as to take interventions to alleviate or reverse the process of fatty liver disease, promote liver health, and then prevent the occurrence of cardiovascular and other complications, reduce the risk of death.
Resources
[1] P. Barton Duell, et al., (2022). Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biology, DOI: https://doi.org/10.1161/ATV.0000000000000153.
[2] Fatty liver disease not caused by alcohol is common – and often missed. Retrieved Apr 26 ,2022,from https://www.heart.org/en/news/2022/04/14/fatty-liver-disease-not-caused-by-alcohol-is-common-and-often-missed
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