Ana Yael
When I was at school, I contracted viral hepatitis, despite never having done any of the things – sharing needles, getting tattooed or having multiple sexual partners – that are the usual risk factors for the disease. My biology teacher took one look at my sick and jaundiced face and told me, sagely, that “the life depends on the liver”.
All I knew at the time was that life with a malfunctioning liver was pretty miserable. That, unfortunately, might now be the fate of an increasing number of people around the world. Liver diseases in general are on the rise, but one in particular is causing concern for doctors and researchers alike – and you have probably never even heard of it. More than a third of adults and around 13 per cent of children and adolescents are thought to have a condition known as non-alcoholic fatty liver disease (NAFLD), among other names – a condition that, if undiagnosed and untreated, puts them on a trajectory towards liver failure and a host of other conditions.
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Not me, surely? Don’t be complacent. Most people with NAFLD don’t know they have it, as the condition is largely asymptomatic and screening programmes almost non-existent. But a concerted effort to raise awareness is under way in the hope of averting a crisis. The bad news is that, on our current trajectory, more than half of the world’s adults will have NAFLD in their lifetime. The good news is that many of these people won’t experience severe disease, and the rest may be able to reverse the problem – but only if it is caught early enough.
The liver is the in the human body and certainly earns its real estate. As well as being the main way that the body neutralises toxins, it also plays a vital role in immunity, digestion and vitamin storage.
Chronic liver disease isn’t a new public health problem, but it has become a moving target. In the past, the main causes of a damaged liver were prolonged alcohol abuse and infection with hepatitis viruses, yet while these have declined due to increased awareness, widespread vaccination, needle exchanges and antiviral treatments, liver disease in general hasn’t. The main reason for that is NAFLD.
What is fatty liver disease?
The possibility of another, unknown, cause of chronic liver disease was first flagged in 1980, when and his colleagues at the Mayo Clinic in Rochester, Minnesota, on what they called “a hitherto unnamed liver disease”. They described 20 people with fatty accumulations in their livers similar to those seen in heavy drinkers; three had significant liver damage. The individuals were non-drinkers, but most were moderately obese. Ludwig and his colleagues dubbed it non-alcoholic steatohepatitis (NASH) (steatohepatitis means fat-related liver inflammation) and said it was of unknown cause. “Currently, we know of no effective therapy,” they concluded.
The report went largely unnoticed for more than a decade. Unhealthy levels of fat in the liver were a known problem, but doctors saw alcohol as by far the most important cause. In the 1990s, however, the report came to be widely cited as obesity rates rose and it . NASH – by then widely known as NAFLD – was recognised as a distinct condition.
Today, NAFLD is the . According to a coalition of doctors called , the worldwide prevalence in adults is 38 per cent and around 13 per cent in children and adolescents. That adds up to about 2.5 billion people.
“The prevalence of the disease has grown dramatically in recent decades,” says at the City University of New York. “The numbers are huge.” In 1990, when fatty liver was starting to be considered as an important public health problem, it was estimated to affect 18.2 per cent of the global population. By 2020, that had more than doubled, and the number is expected to keep on rising. By 2040, , says at Stanford University Medical Center in California.
A cross-section of a liver with fatty deposits in blue SIMON FRASER/FREEMAN HOSPITAL, NEWCASTLE UPON TYNE/SCIENCE PHOTO LIBRARY
This doesn’t mean that all those people will feel physically ill, let alone be aware of their inflamed livers and declining hepatic health. NAFLD is largely asymptomatic beyond mild fatigue and a somewhat achy abdomen. But in around a third of people, the chronic inflammation associated with the condition gradually degrades liver function and can, if left untreated, spiral out of control.
The reason for the greater prevalence is pretty straightforward: there are an increasing number of people who are overweight or obese. Excess weight, particularly when coupled with type 2 diabetes, causes fat to accumulate in adipose cells in the liver. The fat content of a healthy liver is less than 5 per cent by mass. When it exceeds that, it has passed the threshold for NAFLD.
The are rising in parallel across the world, according to at Karolinska University Hospital in Stockholm, Sweden. The World Health Organization says that obesity has nearly tripled since 1975 and that around 28 per cent of the global population are now overweight or obese.
But being a healthy weight isn’t a reason to relax. Around 10 per cent of people with NAFLD have a fatty liver despite their body mass index being in the normal range, a condition called lean NASH. The reason for this is poorly understood, although according to a , it may be that some people have a genetic predisposition to accumulating liver fat.
Lean NASH not withstanding, NAFLD is largely a “comorbidity” of obesity, meaning that it is a secondary outcome of a primary health problem. Obesity’s better-known bedfellows are type 2 diabetes, cardiovascular disease, high blood pressure and cancer, all of which have been the subject of extensive public awareness campaigns.
NAFLD, however, has slipped under the radar, due to what Lazarus describes as “a generalised lack of urgency and policies to tackle the issue” along with low levels of public awareness. According to Lazarus, this is largely because it is so stealthy. “The liver is having trouble functioning, but we’re not feeling it, and that’s a big problem,” he says.
Other factors are involved in the , according to at the University of Birmingham, UK, and an adviser to the British Liver Trust. “There is a lot of stigma associated with liver disease. If you think about the commonest causes – namely excess alcohol, being overweight or obese, or, in the context of viral hepatitis, people that inject drugs – there is stigmatisation even in the profession,” he says. “And we know full well that when you stigmatise a condition, people are less likely to come forward, less likely to access care and, ultimately, it drives poorer outcomes.”
There is also limited availability of simple tests to monitor the progression of the disease, says at the University of Southampton, UK.
A FibroScan could spot signs of fatty liver disease BELMONTE/SCIENCE PHOTO LIBRARY
In 2022, a covering 86 per cent of the world’s population found that not one had a national strategy to address NAFLD. To judge this, the researchers created a “preparedness index” based on six criteria, including data collection, general awareness and the availability of diagnosis and treatment, then scored each country out of 100. India came top with 42.7 and the UK second with 40. But neither nation can be said to be well-prepared. “They failed, but everyone else failed worse,” says Lazarus.
More than a third of countries scored zero, including Ireland, Iceland and South Africa. Across the board, there is “substantial room for improvement”, says Byrne.
Without it, millions of people could develop some pretty awful conditions. What exactly happens after fat builds up in the liver is still a matter of debate, but the problem appears to be related to oxidative stress, which is where we see elevated levels of reactive oxygen species – molecules that cause damage to lipids, proteins and DNA. Oxidative stress seems to build up when fat in the liver is used as an energy source. This subsequently causes inflammation to occur.
Symptoms
For the unlucky ones, the result is fibrosis, the accumulation of tough scar tissue as the liver fights a losing battle against inflammation.
The liver has , with the ability to regrow completely after 90 per cent of it has been removed or damaged. But it has its limits. When scar tissue overwhelms the organ, the result is cirrhosis, which often leads to cancer and liver failure. The symptoms of cirrhosis include jaundice, tiredness and weakness, loss of appetite, weight loss, nausea and vomiting, pain in the right side of the abdomen, itchy skin and swelling of the feet and ankles. Around .
Cirrhosis has also been increasing steadily. Between 2010 and 2019, the . Only about a tenth of those deaths were caused by NAFLD – the majority are still triggered by the hepatitis B and C viruses and alcohol – but whereas viral and alcoholic cirrhosis are gradually declining due to vaccination and alcohol control measures, .
People with NAFLD don’t just have to worry about their livers packing up. The . It is also an , chronic kidney disease and cancers in organs other than the liver.
Fortunately, NAFLD is eminently treatable if caught early enough. “It’s a terrifying situation, but it’s a very fixable situation,” says Lazarus. “For the vast majority, 75 to 80 per cent, at the lower stages of liver disease, we can intervene.” Just last month, the US Food and Drug Administration approved its first drug that could help people with NAFLD, called resmetirom, which reduces scar tissue and other markers of poor liver health – and there are .
For the vast majority of people, lifestyle interventions can reverse the risk of fatty liver disease Don Heupel/Associated Press/Alamy
Meanwhile, lifestyle interventions offer a key solution. The slow burn of NAFLD and the early stages of fibrosis can be arrested or even reversed by losing 7 to 10 per cent of body weight and keeping it off, according to Lazarus. Of course, people who are overweight or obese have probably been told that weight loss would improve their health already, but if they knew they also had a potentially fatal liver disease, that might be extra motivation, he says. The problem is, people generally don’t know because they aren’t tested.
For that reason, Lazarus and others are making a concerted push to drag the disease up the public health agenda. In February, a consortium of more than 40 researchers, led by Lazarus, published a major call to arms titled .
Part of that agenda is to rename NAFLD as – deep breath – , or MASLD, pronounced “mass LD”. One major reason why is that the current name just adds to the stigma already attached to liver disease, with its allusions to both alcohol and fat. “The change in name was in part to make it something that people were more comfortable talking about,” says Newsome.
How to reverse fatty liver disease
Armed with the new name, the plan is to boost awareness of the condition and its causes, and to push for better screening programmes. According to at the Paris Diderot University in France, the condition meets all the established criteria for routine screening, but almost nowhere actually does it.
It can be done: there is a blood test called the enhanced liver fibrosis test, which measures three molecules involved in metabolism that reflect the severity of liver fibrosis. But it is expensive. A cheaper alternative is , which calculates the chance of a person having fibrosis from routine blood test results. “It gives an indication that something might be going on,” says Lazarus. A relatively cheap ultrasound test called a , which can detect both fibrosis and cirrhosis, can be used to follow up.
A in 2019 was so successful that National Health Service Tayside in Dundee now carries out routine screening. But very few health systems have followed suit, says Lazarus. “If I were in charge, I’d be putting FibroScans everywhere.”
Not so fast, say critics. Mass screening is controversial. You want to avoid missing people who are going to develop significant disease, says Newsome, but you also want to avoid chasing those who ultimately aren’t going to develop a liver problem. “It raises anxiety. It consumes resources.” Much better to target those who are known to be at high risk, such as people who are overweight or .
What would really help, says Newsome, is to understand why some people are more susceptible to ending up with more severe liver damage than others. “You can often have two patients the same age, same weight, and both have diabetes, but one will have significant scarring and the other won’t,” says Newsome. Exactly why is unclear, though there are strong signs that it is genetic, he says.
Soon there may be tests that identify who is most at risk of scarring, but screening can’t solve the problem on its own. As we know well, there are many factors that affect people’s weight, such as genetics, hormonal changes and age, as well as lifestyle and economic factors that aren’t necessarily within their control. People also have to act on any advice or support given, which, as experience of trying to halt the epidemic of obesity and type 2 diabetes has shown, can be incredibly challenging. “Most of the strategies to deal with this have failed,” says Newsome. The new generation 0f weight-loss drugs, such as Wegovy, may help, he says.
In the absence of screening, it is probably better to be safe than sorry. Newsome’s advice is that if you think you may be at risk, ask your doctor for a test. But ultimately, the take-home message is obvious: maintain a healthy body weight. Easier said than done in our obesity-promoting environment, but as that wise teacher told me, the life depends on the liver.
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