Fatty Liver Disease, A Diabetes Complication, Deserves More Attention

Nonalcoholic fatty liver disease (NAFLD) is a “silent” disease, with few or zero obvious symptoms.

If you have diabetes, you very well may have this under-the-radar condition without even knowing it: Experts estimate that as many 60-70 percent of patients with type 2 diabetes have it. If you also have obesity, a sedentary lifestyle, or sleep apnea, the chances are likely even higher.

No need to worry quite yet! For most patients with type 2 diabetes, NAFLD only causes moderate metabolic harm, and the consequences are basically indistinguishable from the other issues that already characterize diabetes. And at the moment, the mainstream opinion is that NAFLD should be treated the same way we treat type 2 diabetes: with diet, exercise, and medication designed to correct insulin resistance.

But in an unlucky minority of patients with NAFLD, liver damage will progress to a critical and very dangerous level. Recent research suggests that this is a bigger problem than previously understood, and experts believe that the condition deserves significantly more attention than it gets today, from researchers, family doctors, and patients alike. In 2023, the American Diabetes Association updated its recommendations to encourage more screening of NAFLD, and it may become increasingly normal to discuss the health of your liver with your clinician.

Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease refers to the excess accumulation of fat within the liver itself.

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Although most people associate liver disease with alcohol abuse, NAFLD, as the name implies, is not caused by alcohol. Experts believe that NAFLD is usually caused by the same general factors that cause type 2 diabetes and metabolic syndrome: principally genetics, age, and diet and exercise habits.

NAFLD is highly correlated with metabolic syndrome, which is defined by visceral adiposity (excess weight around the belly), high triglycerides, low HDL (“good”) cholesterol, high blood pressure, and insulin resistance. In fact, it might be right to say that NAFLD is the damage that your liver sustains due to metabolic dysfunction. And just like diabetes and metabolic syndrome, NAFLD is on the rise.

Although the condition often has no discernible symptoms, some patients may experience unexplained fatigue, nausea, loss of appetite, jaundice, and swollen legs, among others.

Partially because NAFLD is so strongly linked to other metabolic issues, especially type 2 diabetes, there is no specific validated treatment for the condition. No medicine has ever been approved specifically for NAFLD, nor have any targeted interventions been embraced. If you’re doing everything you can to treat your diabetes and other metabolic issues, then you’re likely already doing everything you can do to improve fatty liver disease.

NAFLD gets serious and scary when it progresses to nonalcoholic steatohepatitis, or NASH.

Nonalcoholic Steatohepatitis (NASH)

In a minority of patients, NAFLD will get worse and worse: The liver will accumulate more fat, which causes inflammation and scarring of the liver tissue. At a certain point, this liver damage qualifies as a new and more severe condition, nonalcoholic steatohepatitis (NASH).

NASH is considered a “progressive and life-threatening disease.” About a quarter of NASH patients will experience cirrhosis of the liver, but liver cancer and liver failure are also significant potential issues.

NASH can be difficult to diagnose. In the early stages, some patients with NASH remain curiously free of symptoms. Doctors rely on a variety of blood tests and imaging techniques, such as ultrasound and MRI, to suggest the possibility of NASH. A liver biopsy — an expensive and highly invasive procedure — is the only way to be sure.

For all of these reasons, NASH is often only diagnosed when it’s too late to do anything about it. In these unfortunate cases, a liver transplant may be the only option.

Why Fatty Liver Disease Deserves More Attention

Because NAFLD is only occasionally identified in patients, and even NASH can go undetected, the true scope of its impact has been poorly understood to date.

That has begun to change. In 2021, The New England Journal of Medicine published “Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease.” Researchers from Virginia Commonwealth University identified 1,773 patients with NAFLD, sorted them according to the severity of liver damage, and followed them for years.

The study proved that patients with NAFLD and NASH could be stratified into more precise groups according to the amount of fibrosis that they had experienced, giving doctors a useful way of predicting which patients are at a higher risk of advanced liver disease. This could allow doctors to identify which patients would most benefit from intensification of treatment for their metabolic issues.

Meanwhile, there has been a broad movement to improve the way that the global medical community approaches the new “epidemic” of liver disease.

Recognizing the lack of professional consensus on these conditions, the American Gastroenterological Association and seven other professional associations convened an international conference of experts. The results of that conference were published simultaneously in multiple scientific journals, including Diabetes Care in July 2021. The article was titled “Preparing for the NASH Epidemic: A Call to Action.”

The authorities, in short, want the medical community to take the rising prevalence of fatty liver very seriously: the “upward trend in NAFLD/NASH incidence and prevalence underscores the importance and urgency of developing and implementing effective screening, diagnosis, and treatment strategies.”

A press release summarized key findings, among them:

Diabetes is a major risk factor for NAFLD/NASH progression and severity
Primary care providers are the first line of defense, and ought to be trained to identify liver damage early
Lifestyle modification – diet and exercise – is the most effective known treatment

Unfortunately, there isn’t yet a good way of identifying NAFLD and NASH early. Participants in the Virginia Commonwealth University study submitted to liver biopsies, an approach that can’t be realistically applied to the general population. Ultrasound is fairly good at detecting severe liver disease, but less capable of detecting moderate (but still worrying) levels of damage.

Instead, you can expect doctors to increasingly use non-invasive techniques to estimate the degree of liver fibrosity, followed by blood tests and biopsies for those that appear to have significant issues. In the meantime, work continues on novel techniques to diagnose the condition.

Takeaways

Nonalcoholic fatty liver disease (NAFLD) is thought to result from damage sustained by the liver due to metabolic dysfunction. It is extremely common in adults, especially those with type 2 diabetes. Although it’s not necessarily a serious condition on its own, for some patients it will progress to a more severe level of damage known as nonalcoholic steatohepatitis (NASH). NASH can lead to a variety of very bad outcomes, including cirrhosis.

Today there is relatively little screening for NAFLD, and no established treatment beyond the healthy lifestyle guidelines that apply generally to other metabolic conditions, such as diabetes, high blood pressure, and obesity. Authorities are eager to change the situation, and while we are likely years away from effective new screening techniques and treatments, your medical team may begin to take your liver health more seriously in the near future.

Dharmalingam et al. Nonalcoholic Fatty Liver Disease and Type 2 Diabetes. Indian Journal of Endocrinology and Metabolism. May-June, 2018.

American Diabetes Association Releases a Guideline Update in NAFLD (Non-Alcoholic Fatty Liver Disease) and Diabetes. American Diabetes Association [Press Release]. June 25 ,2023.

Kneeman et al. Secondary Causes of Nonalcoholic Fatty Liver Disease. Therapeutic Advances in Gastroenterology. May, 2012.

Younossi et al. The Global Epidemiology of Nonalcoholic Fatty Liver Disease (NAFLD) And Nonalcoholic Steatohepatitis (NASH): A Systematic Review. Hepatology. April 2023.

Non-Alcohol Related Fatty Liver Disease. Cleveland Clinic. February 5, 2022.

What is NASH? The NASH Education Program.

Sanyal et al. Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease. New England Journal of Medicine. October 21, 2021.

Kanwal et al. Preparing for the NASH Epidemic: A Call to Action. Diabetes Care. July 26, 2021.

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