NAFLD ‘not fit for purpose’: Experts debate impact of changing name vs. definition
Click Here to Manage Email Alerts
WASHINGTON — The term ‘non-alcoholic fatty liver disease’ no longer reflects current knowledge of the disease and should be changed, members of the NAFLD Nomenclature steering committee noted during The Liver Meeting.
“I think what was clear in the final round [of panel discussions] was a view that the current name is not fit for purpose,” committee co-chair Philip Newsome, MD, PhD, FRCPE, director of Research and Knowledge Transfer for the College of Medical & Dental Sciences at the University of Birmingham in the United Kingdom, told attendees. “The other thing that I think still needs to be developed is what a change in definition may or may not look like — and that is something we will explore in the next round.”
There has been an ongoing debate for several years regarding whether NAFLD represents a suitable name, considering the term ‘non-alcoholic’ overstates the lack of alcohol use and underplays the significance of metabolic risk factors that drive disease progression. Additionally, ‘non-alcoholic’ has attached a stigma to the term, which has resulted in worse quality of life among patients with NAFLD and less consideration in health policy.
In early 2021, a global effort was launched to determine whether the term ‘NAFLD’ was appropriate or if it needed to be renamed and what the replacement terms could be.
Using the Delphi process, 264 global experts from 56 countries participated in several survey rounds over the past 2 years. In July 2022, 122 participants from 32 countries met to discuss and assessed results of the first three Delphi rounds at an interactive Nomenclature Summit in Chicago. Some survey questions that came from these discussions focused on considerations regarding the term ‘metabolic’ and alcohol use, disease definition and the role of steatohepatitis.
What’s in a name?
According to Newsome, 74% of respondents overall agreed ‘NAFLD,’ was sufficiently flawed and warranted a name change. Additionally, 66% agreed the definition needed changing while 34% did not. Eighty-two percent of respondents felt a definition change would either have no impact or would enhance interpretation and 59% said the change would cause a delay.
“There is’ a consistent trend there,” Newsome, said. “Changing the name doesn’t seem to have an impact but changing the definition may, depending on how that’s done.”
Survey results showed 73% of respondents agreed that a name change would improve awareness or have no effect, whereas 27% said that it would worsen awareness. If both name and definition were changed, 60% said it would hinder interpretation of previous clinical trial results, while 21% said it would have no impact.
“I don’t think anybody wants to push the field backwards here in terms of awareness; there’s an understandable concern that a name change could have an impact on disease awareness,” Newsome said.
Though a high percentage of survey respondents believed a name change would improve disease awareness, Vlad Ratziu, MD, PhD, professor of Hepatology at Sorbonne University and Pitié-Salpêtrière Hospital in Paris, France, noted ‘NAFLD’ is already easily understood by patients.
“I think it’s very important that we recognize that one aspect of the virtue of a name is the ability to convey it easily to patients,” he said. “We explain easily to a patient what this disease is about. I find it simple to say because everybody agrees that obesity or overweight and diabetes and all these metabolic factors are strongly associated with [nonalcoholic steatohepatitis (NASH)]. Even if it’s hard scientifically and you can refine the concept and not agree with metabolic dysfunction ... It fundamentally, by and large, is what characterizes this disease, and it is a very simple way to explain it to the patient.”
‘Metabolic’ may not be meaningful
One possibility for a name change was having an umbrella term that described the presence of fat inside the liver, and within this term would be the different types of conditions. The umbrella term with the highest number of votes was ‘steatotic liver disease’, followed by fatty liver disease, Newsome reported.
“I appreciate that [the term] steatotic liver disease is broad enough that it will allow us to subcategorize as we learn more about this disease,” Manal F. Abdelmalek, MD, MPH, FAASLD, director of the NAFLD Clinical Research Program at Duke University, said. “But this is a challenging area because of the cause/effect relationships and where we currently are, which is still early in phenotyping and genotyping this condition.”
Mary E. Rinella, MD, steering committee co-chair and professor of medicine at the University of Chicago Pritzker School of Medicine, reported that 93% of respondents felt nonalcoholic steatohepatitis resolution should remain an important classifier of disease activity. Eighty-six perfect felt metabolic dysfunction details the central aspect of disease pathophysiology, whereas only 56% believed metabolic dysfunction was a distinctly defined entity, she noted.
Additionally, Newsome said 40% of respondents agreed with having an overarching term that included the term ‘metabolic’.
Donna R. Cryer, JD, founder and CEO of the Global Liver Institute, and a 28-year liver transplant survivor, said that progress could be made with any name as long as it does not cause confusion; however, she believes ‘metabolic’ is not needed in the name.
“Metabolic starts to be not meaningful because it is so pervasive across so many different conditions,” she said, “I absolutely understand that it’s very natural to explain this condition by its connection to obesity and diabetes, and we must continue to do so. [However,] having metabolic in the name is not necessary it’s not helpful.”
As Newsome noted, the definition may not be changed or only subtly changed, despite the fact that 99% of patients seen by hepatologists will likely have features of metabolic syndrome. “So in that sense, a potential change in definition would actually not move the needle too much,” he added.
Moving forward
The next steps in the process, Rinella said, will include a few short surveys sent out to finalize the main questions on NAFLD nomenclature. The findings will be articulated in narrative form and then followed by public comment.
Cryer recommended that the committee work closely with the FDA to clarify and limit any delays on the use of existing data, as well as use the opportunity of nomenclature revision to meet all the criteria when determining a name.
Additionally, she suggested the committee develop a new or neutral name that references ‘fat’ in some form while following the classic naming structure seen in hepatology. Lastly, she recommended the committee use a nomenclature schema that includes disease subtypes and then graduations/severity classification within those subtypes and issue a time defined change process including a report on the impact.
She concluded with, “What is important is that the field move forward together on behalf of the patients.”
Collapse
Pan-society presentation of NAFLD nomenclature consensus process. Presented at: The Liver Meeting; Nov. 4-8, 2022; Washington (hybrid).
Click Here to Manage Email Alerts