▎ WuXi AppTec content team editor
The American Heart Association (AHA) recently issued a scientific statement stating that non-alcoholic fatty liver disease (NAFLD) has become an increasingly common chronic progressive disease and affects more than 25% of adults worldwide. At present, the vast majority of NAFLD cases have not been fully diagnosed, and its important risk factor for the onset and death of atherosclerotic cardiovascular disease (ASCVD) has not been recognized.
In the future, it is necessary to improve diagnostic strategies to better identify NAFLD and further determine the best treatment strategies for preventing liver and cardiovascular complications of NAFLD. The statement was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, owned by AHA.
Screenshot source: Arterioscler Thromb Vasc Biol
Risk factors for NAFLD
The statement noted that the risk factors for NAFLD mainly include:
Metabolic/endocrine factors: eg, insulin resistance, impaired glucose tolerance or diabetes mellitus, hypertriglyceridemia (especially imbalances in the production and clearance of liver triglycerides), visceral obesity, metabolic syndrome, polycystic ovary syndrome, chronic kidney disease, disorders of fat metabolism, hypo-β-lipoproteinemia (due to apoB deficiency), lysosomal acid lipase deficiency, defects in oxidation of mitochondrial fatty acids (congenital and acquired);
Drug factors: alcohol, amiodarone, aspirin (eg Reye's syndrome), corticosteroids, lometaparamita, mipomethen, NSAIDs, reverse transcriptase inhibitors, tamoxifen, tetracycline, valproic acid;
Genetic factors: nafld family history, genetic variants (e.g., genes GCKR, MBOAT7, PNPLA3, TM6SF2, HSD17B13);
Lifestyle factors: Poor lifestyle also plays an important role in the occurrence and development of NAFLD. For example, poor eating habits not only promote the occurrence of hypertriglyceridemia, hyperglycemia, insulin resistance, and weight gain, but also show a clear correlation with an increased risk of DEVELOPING NAFLD.
NAFLD doesn't just hurt the liver
BASED ON NAFLD is associated with insulin resistance (whether accompanied by diabetes mellitus or not), obesity (especially visceral obesity), metabolic syndrome, dyslipidemia (including hypertriglyceridemia, elevated free fatty acids, decreased HDL-C, and elevated small and dense LDL). Therefore, there is a clear correlation between the increase in the incidence of NAFLD and the increase in the rate of obesity and the incidence of metabolic syndrome.
However, although metabolic syndrome and NAFLD share some of the same risk factors, clinically patients may have metabolic syndrome alone without NAFLD, or NAFLD alone without metabolic syndrome.
In addition, while diseases such as type 2 diabetes may be associated with an increased risk of developing NAFLD, the correlation is two-way, i.e., NAFLD is also associated with an increased risk of developing type 2 diabetes. Based on the co-pathogenic effects of visceral obesity and insulin resistance in NAFLD and type 2 diabetes, there is also an interconnection between these diseases.
It is worth noting that NAFLD is not only an independent risk factor for ASCVD, but also in patients with severe NAFLD, the risk of ASCVD-related risk diseases (such as diabetes, hypertension, etc.) is also significantly increased, that is, NAFLD can enhance the risk effect of ASCVD.
In addition, although the results of previous meta-analyses suggest that NAFLD is associated with an increased risk of all-cause death and not with an increased risk of death from cardiovascular disease. However, recent analytical studies have confirmed that liver fibrosis (F3 to F4) is associated with an increased risk of liver complications and all-cause death, and ASCVD is the leading cause of death in patients with NAFLD.
▲Summary of research results on the association between NAFLD and ASCVD risk (Image source: Reference[1])
Detection of NAFLD
If NAFLD is not diagnosed by specific tests, it usually does not show significant symptoms until NAFLD progresses to advanced, potentially irreversible liver damage.
Liver biopsy is the gold standard for diagnosing NAFLD and NASH, but this method is not only more expensive, but also poses an increased risk of complications. Aspartate aminotransferase (AST) and ALAN aminotransferase (ALT) levels are not effectively used in the diagnosis of NAFLD due to their low sensitivity and specificity, and the fact that transaminases levels in many patients with NAFLD can also be maintained at normal levels.
At present, the imaging strategies of NAFLD mainly include liver ultrasonography, liver vibration control transient elastography (VCTE), CT and MRI. Liver ultrasonography is also relatively less sensitive in the examination of hepatic steatosis, and clinical use of liver ultrasonography may result in missed diagnosis of NAFLD.
Non-invasive diagnostic tools such as VCTE tests can provide a quick and easy way to assess effective results, but are not yet widely used.
The vast majority of patients with hepatic steatosis do not progress to NASH, cirrhosis, or hepatocellular carcinoma, but there are some patients who do. It is not yet possible to determine which part of the patient will develop disease progression, so imaging studies combined with liver biopsy may become key to monitoring the severity and progression of the disease.
INTERVENTION FOR NAFLD
The statement states that the objectives of NAFLD intervention are, inter alia:
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.
Current lifestyle interventions such as dietary interventions, abstinence from alcohol, increased exercise levels, and weight control (weight loss of 5% to 10%) are key interventions for NAFLD.
In terms of treatment, the current statement describes potential therapeutic agents for current NAFLD, such as pioglitazone, liraglutide, smeglutide, metformin, lipid-lowering drugs (such as statins), leptin, vitamin E, farnigol X receptor agonists, etc.
Although there are many drugs that have shown considerable efficacy in the treatment of NAFLD, none of them have yet been approved by the FDA. A large number of prospective randomized clinical trials are currently underway to evaluate the safety and efficacy of these drugs in alleviating hepatic steatosis or preventing progression to liver fibrosis and cirrhosis.
The statement stressed that liver complications of NAFLD include non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. In addition to these serious complications, NAFLD is also a risk factor for atherosclerotic cardiovascular disease (ASCVD), which is also the leading cause of death in patients with NAFLD.
Given the essential role of statins in the primary and secondary prevention of ASCVD, the statement notes that despite clinical findings, statin treatment may cause a lower risk of elevated liver transaminases. However, there is good evidence that statins are safe in patients with hepatically functioning NAFLD.
In addition, new drugs for different pathogenic stages of NAFLD are currently being developed, but the efficacy of the vast majority of these drugs is still not impressive, and therapeutic toxicity has become a limiting factor for the application of these drugs. The statement stressed that further research is needed in the future to determine the best treatment strategies for preventing liver and cardiovascular complications of NAFLD.