Do you have fatty liver disease?

By the summer of 2019, Jackson Griffiths, then 42 years old, had been feeling tired and lethargic, off and on, for about five years. Yet nothing had been flagged as abnormal in medical checkups.

But then the British holiday company executive based in London suddenly developed swelling and a rash on his legs. This time, after running tests, Griffiths’ doctor informed him he had type 2 diabetes.

Over the next several months, as Griffiths adjusted to the diagnosis by learning to test his blood sugar and keep it steady by eating more regularly, his doctor sent him for more tests. They were looking for conditions that often crop up in people with diabetes, such as heart disease and liver or kidney problems.

In early 2021, after an ultrasound of his liver to check for fat and scarring, followed by a liver biopsy, Griffiths got some alarming news: He had something called non-alcoholic fatty liver disease (NAFLD).

With this condition, the organ damage looks similar to that caused by heavy drinking, but the actual cause is steatosis—a buildup of excess fat in the liver so that it accounts for more than five to ten percent of the organ’s weight.

NAFLD progresses in stages. A fat build-up (stage one) triggers inflammation (stage two), which, over many years, can cause scarring (stage three), also known as fibrosis. The scarring interferes with normal liver function. If a high amount of scar tissue and nodules form, making the liver harder, it’s classified as cirrhosis, or stage four. Cirrhosis carries a high risk of liver cancer and can eventually lead to liver failure, which necessitates an organ transplant.

Griffiths, who had never been a heavy drinker, was at stage three, with significant scarring of his liver, and was well on his way to reaching the threshold for cirrhosis. “I was in such shock that I didn’t register what the specialist was telling me,” he recalls. When he asked the doctor if it was a long-term condition, the answer was yes. “I thought, I’m in trouble here. I’m not going to get better.”

It was only when Griffiths reached out to the charitable organisation British Liver Trust for support that he learned he could gradually reverse some of the damage if he made lifestyle changes and lost weight. “I realised that I had to do something,” he says.

Griffiths didn’t always eat well or exercise, so he was overweight; he’d hovered around 20 stone since his mid-20s. He consulted a dietitian to learn about healthy eating and added new foods to his diet, like quinoa, kimchee and wild salmon. He began walking in the park and swimming. He even connected with a therapist to help him handle work-related stress. Now 46, Griffiths lost more than two stone in the year following his diagnosis.

He also began participating in online support groups hosted by British Liver Trust, where he could talk with other people living with NAFLD.

“That has helped me deal with the diagnosis,” he says. “It’s comforting and it’s grounding.”

When you're obese your liver can also get fat. Illustration credit: Stuart Briers

A diagnosis of NAFLD usually comes as a surprise to patients, says Dr Eline Wouters-van den Berg, a researcher and resident in gastroenterology and hepatology at the University Medical Center Groningen in the Netherlands. “Everybody knows there’s an obesity epidemic, but people don’t know that organs also get fat.”

The liver is particularly susceptible because, among its many functions, it makes and stores fats. When we take in too many calories while sedentary, it creates an imbalance, causing fat in the liver to build up, which can lead to the organ’s inflammation. That can result in scarring and cirrhosis.

“I was a comfort eater,” acknowledges Griffiths, who habitually reached for cake or sugary soft drinks during times of stress. Besides obesity, metabolic conditions such as type 2 diabetes and high levels of triglycerides (a type of fat that can be measured in a blood test) are strongly associated with fatty liver. The list of risk factors also includes high blood pressure, high cholesterol and sleep apnea.

While fatty liver disease was once an uncommon diagnosis, it’s been skyrocketing as obesity rates have risen around the world. Data from 17 countries, collected for a study published in The Lancet Gastroenterology and Hepatology in 2022, estimated that the prevalence rate of NAFLD rose by more than 12 percent from 2005 to 2016.

Today, the condition affects as much as one third of the adult population, with the highest rates showing up in countries where obesity is common. According to current estimates, as many as one billion people worldwide have NAFLD. Wouters-van den Berg’s own research found that 22 percent of Dutch adults are suspected of having it. “That’s millions of people with fatty liver disease,” she notes. And most never realise it.

Not everyone with stage-one NAFLD will go on to develop scarring and worsening liver disease, however. Estimates range widely, from three to 40 percent, depending on the populations being studied. And although researchers have uncovered a few clues, they still don’t know exactly how to identify the people most at risk of developing cirrhosis.

Genetics can play a role, says Dr. Hannes Hagström, a researcher in the epidemiology of NAFLD and a consultant in hepatology at Karolinska University Hospital in Sweden. “For instance, there are mutations of a particular gene that tend to be associated with a higher degree of liver fat,” he says. This might help explain “lean NAFLD,” the ten per cent of people with the condition who aren’t obese. Drinking alcohol, even in moderate amounts, can aggravate NAFLD in someone already at elevated risk.

Fatty liver disease can lead to strokes and heart attacks. Illustration credit: Stuart Briers

But there’s another significant reason that not everyone with NAFLD is destined for liver failure: Those who have it are at 37 per cent greater risk than average for cardiovascular events like stroke or heart attack, which are more likely to kill you first since liver disease advances slowly. Says Hagström, “It can take 20 years or more for someone with NAFLD to develop cirrhosis.”

It’s not clear whether NAFLD worsens cardiovascular disease or vice versa—or whether these conditions just share a lot of the same risk factors. (In fact, they’re so interconnected that many experts now prefer to call the condition “metabolic associated fatty liver disease,” or MAFLD.)

Even if it takes decades to reach end-stage liver disease, NAFLD takes a toll over those years. “These patients have a measurable impairment in quality of life. They do not feel as well,” says Dr. Jörn Schattenberg, who practises gastroenterology and hepatology at the Mainz University Medical Centre in Germany. “They are also less productive and are absent from work more often.”

Since an early diagnosis can provide an opportunity to heal some of the damage, and even be lifesaving, it’s critical the condition doesn’t go undiscovered. Unfortunately, symptoms may be silent or non-specific in the early stages of inflammation: a bit of fatigue, maybe, or a vague ache in the upper right abdomen.

“Anybody can have those symptoms,” says Schattenberg. “If you have left-sided chest pain, you think it’s a heart attack. But when it’s right-sided discomfort, and a little tiredness, very few people will think of liver disease.”

Unlike other illnesses, such as breast cancer, there’s no routine screening for NAFLD. And while it may be straightforward to figure out who is likely to have a fatty liver based on risk factors like their waist circumference, cholesterol levels and blood pressure, traditionally the only definitive way to assess the disease has been a biopsy. But extracting a liver sample with a needle to check for fat content, inflammation and damage is costly and invasive. It can lead to serious complications like bleeding—and can even be inaccurate.

“Biopsy isn’t a feasible approach for large-scale screening, especially given the high prevalence of the disease,” says Dr. Michele Vacca, who works at the Roger Williams Institute of Hepatology at London’s Foundation for Liver Research, and at the University of Bari in Italy.

Technology is enabling new diagnostic approaches for NAFLD. Illustration credit: Stuart Briers

One non-invasive option is imaging, which has recently become more advanced. In wide use only within the last five to ten years, a specialized ultrasound, sold under the brand name FibroScan, can evaluate the level of liver scarring and track its progress. (It’s the test that Griffiths got that led to his diagnosis.)

Another exciting new area of diagnostics involves looking for biomarkers in a non-invasive way: through patterns that show up on MRIs and in blood and urine, for instance, and which have the potential to provide more precise information. This field has become more high-tech in recent years, with machines that can analyze specific molecules.

Many researchers around the world, including Vacca and his colleague in London, Dr. I. Jane Cox, are on the hunt for biomarkers that could not only assess the stage of damage but also reliably predict who is likely to develop serious disease, or could benefit from a future drug treatment.

Cox says identifying NAFLD early would have significant benefits. “Timely diagnosis, ideally by a simple blood test or urine dipstick test, might allow the patient to clear excess fat from their liver with changes in diet and exercise.”

She adds that even though their research requires expensive equipment, it may eventually lead to a cheap urine test that could be widely used in under-resourced areas.

Excercise, healthy food and losing weight are ways to tackle fatty liver disease. Illustration credit: Stuart Briers

Aside from lifestyle changes, there are some promising pharmacological treatments being tested, says Vacca. But only bariatric surgery (also called gastric bypass surgery) has proven to slow the disease’s progression. It’s a major step—one that some people choose so they can limit the amount of food they eat or the calories they absorb.

A 2021 study at the Bariatric and Metabolic Institute in the United States found that in NAFLD patients with liver fibrosis who underwent bariatric surgery, the risk for advanced liver disease was reduced by 12.4 per cent over the next ten years. That’s almost as much as it was reduced for serious cardiovascular events (13.9 per cent).

For Jackson Griffiths, despite his weight loss in 2021, he ended up gaining some of it back. “I lost my discipline and focus,” he admits. So he had the surgery in early 2023. He lost three and a half stone in the first five weeks after the operation, and is hopeful that weight loss will keep his liver condition under control.

While there is no drug for treating or curing NAFLD, researchers are experimenting with new drug therapies that block the ability of fat to cause cell damage, slow the formation of fibrosis and control inflammation. Although a handful of medications are in phase 2 or 3 clinical trials, none has been approved yet for treating NAFLD. It’s a slow-moving disease, so it takes time to prove that an experimental treatment may save lives.

“But,” Schattenberg notes, “even if there were a drug, you wouldn’t want to treat someone with it if you could use a less invasive and better measure—like adopting a healthy lifestyle.”

Currently, that’s the best advice for newly diagnosed individuals: focus on losing weight, eating healthy foods and exercising regularly. It’s also a good idea to reduce or eliminate drinking, since alcohol not only contributes to NAFLD, but also adds calories.

Because better nutrition and regular exercise lead to weight loss—ideally in a gradual process, since there is some evidence that rapid weight loss can worsen the disease for reasons not fully understood—the fat imbalance in the liver will also improve, and the inflammation will heal.

“Even a small amount of weight loss could lead to significant decrease of fat, or even scarring, in the liver,” says Wouters-van den Berg. “A weight loss of ten per cent, which isn’t a lot, has a higher than ten per cent effect on liver fat reduction, and will help tremendously. That’s important to know.”

Banner illustration credit: Stuart Briers

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