Renamed, common liver diseases might get fairer shake at treatment, researchers hope

A slate of liver diseases got a rebrand this year. Experts hope the change can generate more conversation — and research interest — for conditions that still lack treatments.

A group of over 200 physicians, public health experts, industry representatives, regulatory officials, and patient advocates made the call in a supermajority vote: Non-alcoholic fatty liver disease, or NAFLD, would be renamed metabolic dysfunction-associated steatotic liver disease. MASLD for short (pronounced MAA-zuld). 

Only two of the acronym’s letters changed, and yet it was an edit decades in the making. For years, liver doctors and patient advocates had been pointing out how outdated the name was: non-alcoholic fatty liver disease. 

It was a term coined in the 1980s, after Jurgen Ludwig and colleagues used “non-alcoholic steatohepatitis” to describe a liver beaded with extra fat, but whose disease happened in the absence of heavy alcohol drinking. The condition was meant to stand in contrast to the original “fatty liver” disease, which was caused by drinking (and coined around 1845). NAFLD was defined as a condition of exclusion, meant to be used only if other diagnoses weren’t present. 

Decades passed, and neither the nomenclature nor the diagnostic criteria evolved. Even though the American Association for the Study of Liver Diseases suggested replacing NAFLD/NASH with “metabolic steatohepatitis,” members didn’t embrace the new term. Several other researchers and liver groups, including the European association, made similar recommendations, but all fell flat. 

Meanwhile, rates of “fatty liver” gradually began rising. By the late 2010s, MASLD was becoming a full-blown threat, a leading cause of liver failure and need for transplant, a disease costing the U.S. health care system about $100 billion annually. It had also become evident that MASLD could exist alongside other forms of liver disease, such as hepatitis or alcohol-associated illness.  

In 2020, an international group convened to come up with new nomenclature for the condition. Over 70% of the voters chose a slight change: metabolic associated fatty liver disease. A few months later, a separate paper highlighted the long trail of criticisms. Renaming “fatty liver” would go “far beyond a mere semantic revision” and could catalyze a move toward better understanding of the disease, the authors wrote in the journal Liver International. 

The name trivialized the disease and was scientifically inaccurate, they argued. And it would sometimes make patients feel bad to hear “fatty” or a tie to alcohol. “They hear the word ‘alcoholic,’” said Shehzad Merwat, a transplant hepatologist at McGovern Medical School at UTHealth Houston (who was not involved in the renaming).

Jonathan Stine, director of the Fatty Liver Program at Penn State Health, said he’s seen the effect on patients firsthand. “I’ve had patients hear the word ‘fatty’ before, become very emotional, sit with me, cry in the office,” he told STAT.

Liver diseases of all kinds are complex, and even an illness that might seem straightforward — like MASLD — can be caused by various drivers, and show up in many different ways. It’s more of a spectrum, experts told STAT. The patients are heterogeneous, and research suggests even the fat in sickened livers can be made up of different lipid combinations depending on the person. 

While only about 4.5 million adults in the U.S. have a diagnosis of liver disease, some estimates suggest a quarter of the nation’s adult population might unknowingly have MASLD or another liver condition. About 20% of those with MASLD are thought to have a more severe form of the disease, marked by liver scarring and inflammation. (That subcategory, non-alcoholic steatohepatitis, better known as NASH, is now called metabolic dysfunction-associated steatohepatitis, or MASH.)

But some in the field had reservations. Was the change happening prematurely? Writing in 2021 in the journal Hepatology, some experts said such a major change could create confusion at a time when hepatology was already struggling to inform patients and to create successful clinical trials. The authors recommended a formal group be assembled to arrive at consensus.

In a two-year process, experts from the American Association for the Study of Liver Diseases, and its European and Latin American counterparts — as well as people from 50 countries — found a path forward. They didn’t stop at MASLD and MASH. A new category, called metabolic dysfunction associated and alcohol associated liver disease, or MetALD (pronounced Met A-L-D), was created to capture patients who have MASLD and consume more than 210 grams of alcohol each week, the equivalent of about two to three beers per day (the cutoff differs by gender). 

Norah Terrault, president of the American group, said teasing out the MetALD “gray zone” wasn’t part of the plan, but ultimately emerged as a priority since that group is not well-studied. 

For an overarching term, the group decided on steatotic liver disease, shortened to SLD. 

Overall, the process was meant to clarify what a disease was, rather than what it wasn’t. The old nomenclature “was not really reflecting the underlying pathology,” Terrault said. 

Some physicians continue to critique the new terms as unnecessary, or an attempt to be politically correct. But for the couple of hundred experts who took part in the process and their supporters, the new names and definitions are simply more accurate, which could help the field of liver study get specific about its patient populations.

“You have to respect everybody’s viewpoint, but sometimes you have to give things time and see where things land,” said Rohit Loomba, who helped hash out the new terms and will be renaming his University of California San Diego research center accordingly. “If something is ineffective, it will not last the test of time,” he said. (Stine’s program at Penn State will also be renamed.)

Liver diseases, and their accompanying pharmaceutical sprints, have long been stuck in a fruitless cycle. Trial after trial has failed. Although researchers have some ideas, there’s still no treatment to reverse the intense scarring characteristic of severe liver disease. Some suspect this lag has to do with the way trial participants are selected — their disease graded and sorted into buckets depending on the severity of scarring without regard for how the injury happened. The old nomenclature did nothing to help break that pattern, some experts say. 

In recent weeks, the first batches of studies with the new terminology have been published. Medical journals are updating their style guides, and regulatory bodies will recognize the new nomenclature, Terrault said. The liver groups are also coordinating with the Centers for Medicare and Medicaid Services to make sure no systems are disrupted by the shift. The vast majority of patients diagnosed under the former definition of MASLD will meet the new criteria, according to the group’s analysis. The transition should be pretty seamless, she said, even if the full MASLD name takes some getting used to: “It is a bit of a mouthful.” 

The true challenge will be educating patients and providers about the names. 

Several surveys have shown just a small percentage of adults in the U.S. are aware of MASLD (the surveys were done before the nomenclature change), and data suggest it’s an underdiagnosed condition. Terrault said the AASLD is developing informational materials for primary care providers and patients, including adolescents and their parents. 

“I’m really hopeful that the nomenclature is an opportunity for us to help the community and every adult, every child, to be aware of their liver, that liver health matters,” she said. “That steatotic liver disease — and they’re going to get used to that term — is common.”

Historically, names of diseases have been altered under a few different circumstances. Wegener’s granulomatosis, for example,  was renamed granulomatosis with polyangiitis because its namesake had strong Nazi ties. Infectious diseases have been renamed as more information emerges, as was the case with mpox, or HIV/AIDS, which was initially called gay-related immune deficiency. 

Other illnesses, named for peoples (Spanish flu) and places (Ebola) and whole subspecies (hello, swine flu), have made the World Health Organization ask for a bit more care in naming diseases. Prejudices have long seeped into the names of sicknesses. In 14th century Europe, for example, syphilis had a different informal name depending on the region and its nemesis. The French called it “Neapolitan disease,” the Italians “the French disease,” the Russians dubbed it “the Polish disease” and the Polish named it after Germans.

While nomenclature often evolves over time in medicine, it is less common for such change to happen in one fell swoop. Except in the world of liver disease. In 2015, the name of another liver condition, primary biliary cirrhosis, was changed to primary biliary cholangitis. “Cirrhosis” was thought to be a confusing term in the name, since some patients might not have such a degree of permanent scarring at the time of diagnosis.

The time it took from initial complaints to the name change? About 56 years. 

STAT’s coverage of chronic health issues is supported by a grant from Bloomberg Philanthropies. Our financial supporters are not involved in any decisions about our journalism.