CHARLOTTE, N.C. – Metabolic and genetic risk factors for nonalcoholic fatty liver disease (NAFLD) vary across the age spectrum, but once steatosis has started, the risk of progression to cirrhosis is similar for both young and old, investigators found.
At a large Midwest medical center, younger adults were more likely than older patients to have a high-risk gene variant predisposing carriers to NAFLD. And they were less likely than their senior counterparts to have metabolic risk factors, reported Matthew J. Miller, MD, a 3rd-year resident in the department of internal medicine at the University of Michigan Hospital in Ann Arbor.
“Progression to cirrhosis was similar in patients younger than 40, compared to older patients, suggesting NAFLD in the young should not be considered more benign than in older patients,” he said in an oral abstract presented at the annual meeting of the American College of Gastroenterology.
MDedge News/Neil Osterweil
Dr. Matthew J. Miller
The prevalence of NAFLD among younger adults is increasing, but it’s still unknown whether the course of NAFLD is more benign in these patients than in older adults.
In addition, the rate of progression to cirrhosis in patients with NAFLD can vary, making it difficult to predict those patients most at risk for advanced liver disease, Dr. Miller said.
He and his colleagues sought to characterize genetic and metabolic risk factors for NAFLD and their effects on disease progression in patients from 18 to 40 years, 40 to 59 years, and 60 and older.
The investigators collected data on patients with documented objective evidence of NAFLD seen at the Michigan Medicine health care system from 2010 through 2021.
They identified NAFLD by hepatic steatosis on imaging, biopsy, or transient elastography in the absence of other chronic liver diseases, with the earliest date of a hepatic steatosis diagnosis determined to be the index date.
The investigators determined the presence of cirrhosis using validated International Classification of Diseases version 9 or 10 codes, with incident cirrhosis defined as any new cirrhosis diagnosis at least 1 year after the index date.
They also looked at the frequency of known NAFLD risk alleles in a subset of patients with available genetic data.
They divided 31,505 patients into three age groups for comparison: 8,252 patients age 18-39 at the time of steatosis identification, 15,035 age 40-59, and 8,218 age 60 or older.
Of the full cohort, 804 had cirrhosis at the index date, and 388 others developed incident cirrhosis during 128,090 person-years of follow-up.
The prevalence of hypertension, hyperlipidemia, and diabetes were significantly lower in the youngest group, compared with the two older groups, but the youngest patients had a higher prevalence of obesity than the other two groups, with a significantly higher prevalence of class 3 (morbid) obesity.
Of the 4,359 patients with genetic data available, the NAFLD-promoting PNPLA3-rs738409-G allele was more common in the young, compared with the other two age groups (P = .016).
When the investigators looked at the ability of three laboratory tests – the AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB4), and NAFLD fibrosis score for identifying prevalent cirrhosis – they found that the scores performed similarly for patients in the 40-59 group, but the NFS did less well among patients in the 18-39 group. There were no significant differences among the three age groups in the risk for incident cirrhosis over 10 years.
The study helps to answer some of the questions surrounding differences in risk factors across the age spectrum, commented Patricia Jones, MD, MSCR, from the University of Miami.
“We wonder how these people with fatty liver are different. Do younger people have a more malignant course? Are they going to progress more rapidly than others, or not? Because if you think of a disease like fatty liver or for that matter any metabolic syndrome–based disease, it’s a spectrum and a continuum, and by the time you’re diagnosed you’ve already had that condition, so it’s really more interesting to me when people are diagnosed, because diagnosing at a younger age allows you to intervene earlier,” she said in an interview.
Dr. Jones said that she was also interested in exploring how the genetic data might be used to improve care for patients, perhaps by testing for the high-risk allele in routine clinical practice.
“It will be interesting to see how people with this allele progress, independently of whether they’re diagnosed at 40, 50, or 60,” she said.
Dr. Jones was a moderator of the session where Dr. Williams presented his data.
Comoderator Mitchell A. Mah’moud, MD, FACG from Duke University in Durham, N.C., commented in an interview that, “with the medications we have available, maybe we can target these patients and prevent progression to cirrhosis and some of the decompensation that we see.”
The study authors did not disclose a funding source. Dr. Miller, Dr. Jones, and Dr. Mah’moud all reported having no relevant financial disclosures.