New findings 'expose a critical blind spot in liver disease classification'

In a cross-sectional and longitudinal analysis, adjustment for alcohol underreporting resulted in higher estimates of alcohol-related liver disease (ALD) and metabolic dysfunction–associated alcohol-related liver disease (MetALD) than previously recognized. The findings, published in The Lancet Gastroenterology & Hepatology, also showed that type 2 diabetes and binge-drinking were leading mortality risk factors across the steatotic liver disease spectrum.

“[These findings] expose a critical blind spot in liver disease classification. Routine underreporting of alcohol consumption when obtaining medical history means many patients with ALD or MetALD are being misclassified as MASLD [metabolic dysfunction–associated steatotic liver disease]. After correcting for this, the prevalence of ALD and MetALD nearly doubled,” lead author Zobair M. Younossi, MD, MPH, of Georgetown University School of Medicine, Washington, DC, said in an interview with GI & Hepatology News.

Based on these findings, the investigators wrote that “a careful integrated approach to steatotic liver disease with improved assessment of alcohol consumption, metabolic risks, and noninvasive tests is needed to develop better patient-centered care pathways and public health policies.”

“Don’t rely on self-reported alcohol intake alone. Use AUDIT or PEth testing, probe specifically for patterns of binge-drinking, and treat alcohol reduction and cardiometabolic risk management together, not sequentially,” Dr. Younossi said.

Impact of alcohol underreporting

Among 41,100 adults, adjusted prevalence rose from 1988 to 1990 and 2021 to 2023, increasing from 12.7% to 28.2% for MASLD, from 1.6% to 4.1% for MetALD, and from 2.3% to 4.6% for ALD (P < .0001 for all). In 2021 to 2023, uncorrected prevalence was 1.7% for ALD and 2.1% for MetALD, which the investigators noted suggested substantial underreporting of alcohol use.

In 410,293 person-years of follow-up, premature mortality was 2.21-fold higher in ALD (P = .0002), 1.45-fold higher in MetALD (P = .031), and 1.39-fold higher in MASLD (P = .0062) compared with abstainers without steatotic liver disease. These corresponded to rates of 14.91, 8.74, and 7.86 per 1,000 person-years, respectively, versus 4.76 per 1,000 person-years in the reference group.

The investigators found that type 2 diabetes was the strongest metabolic predictor of premature mortality in MASLD, with a population attributable fraction ranging from 13.3% to 44.8%; binge-drinking was reported to be the dominant driver in MetALD (21%) and ALD (92.9%). The highest mortality risk was observed among individuals with concurrent binge-drinking and either type 2 diabetes or hypertension — a combination described by Dr. Younossi as “the most dangerous,” associated with up to a 17-fold increase in mortality risk.

“These findings underscore the urgent need for targeted public health and clinical interventions, which should include systematic screening for alcohol consumption, particularly binge-drinking, as well as comprehensive assessment of cardiometabolic risk factors,” the investigators noted. “Additionally, educational initiatives are needed to increase awareness of the synergistic and potentially deleterious interaction between alcohol use and type 2 diabetes in accelerating liver disease progression and worsening liver-related outcomes.”

As a bottom line, Dr. Younossi said, “Misclassification due to underreported alcohol is common and clinically consequential. Structured alcohol assessment alongside metabolic risk management should become standard care.”

Study details

The investigators analyzed data from the US National Health and Nutrition Examination Survey (NHANES) from 1988 to 2023, including adults aged at least 20 years who completed both interview and examination components and had sufficient data to classify steatotic liver disease and alcohol use.

To evaluate prevalence trends, the investigators analyzed repeated cross-sectional NHANES cycles, including NHANES III (1988–1994) and continuous cycles from 1999 to 2023. For mortality analyses, participants from NHANES III (1988–1994) and NHANES 1999 to 2014 were included, as these cycles were linked to the National Death Index for prospective mortality follow-up through December 31, 2019.

Alcohol intake, obtained by self-report, was adjusted for sex- and frequency-specific underreporting and calibrated to national per capita ethanol consumption. Binge-drinking was defined as at least five drinks on a single occasion at least once in the past year. Steatotic liver disease was defined using ultrasound, the US Fatty Liver Index, or vibration-controlled transient elastography, depending on data availability.

Adjusted hazard ratios for premature mortality (≤ 75 years for men and ≤ 80 years for women) were estimated using Cox proportional hazards models, and population attributable fractions were derived from these models and exposure prevalence.

The study was funded by the Center for Outcomes Research in Liver Disease. Author disclosures can be found in the published research article.