MetALD Associated with 30% Greater Risk of Cancer-Related Mortality than MASLD

Karn Wijarnpreecha, MD, MPH

Credit: Karn Wijarnpreecha on LinkedIn

Patients with metabolic dysfunction and alcohol-associated liver disease (MetALD) may be at a greater risk of cancer-related mortality compared to those with metabolic dysfunction-associated steatotic liver disease (MASLD), according to findings from a recent study.¹

The longitudinal cohort study followed more than 5000 patients with steatotic liver disease (SLD) from the National Health and Nutrition Examination Survey (NHANES) for 10 years and found those with MetALD had a 30% increased risk of cancer-related mortality compared to those with MASLD, suggesting the need for regular cancer surveillance and accurate classification of alcohol consumption in this patient population.¹

Formerly known as nonalcoholic fatty liver disease (NAFLD), MASLD is currently the most common chronic liver disease, affecting more than 30% of the adult population globally. The nomenclature changed from NAFLD to MASLD in 2023, and with this revision came a new entity termed MetALD, comprising individuals who have metabolic risk factors constituting MASLD but consume > 20 g/day (and < 50 g/day) of alcohol for women and > 30 g/day (and < 60 g/day) of alcohol for men.2 Given the novelty of MetALD, little is known about its impact on long-term outcomes versus MASLD.¹

“Binging of alcohol can promote liver injury and steatosis, especially in individuals with MASH,” Karn Wijarnpreecha, MD, MPH, a transplant hepatologist and associate clinical professor in the division of gastroenterology at the University of Arizona, and colleagues wrote.¹ “However, the effects of alcohol consumption on long-term survival outcomes in patients with MASLD, defined using the new cardiometabolic criteria, have yet to be described in the existing literature. Furthermore, there is limited literature on the effects of alcohol use on patients with steatotic liver disease (SLD).”

To compare longitudinal outcomes in patients with MASLD versus MetALD, investigators examined data from NHANES 2011-2018. They defined steatosis according to the United States Fatty Liver Index (US-FLI) as ≥ 30. MASLD was defined as the presence of hepatic steatosis with metabolic dysregulation, including body mass index (BMI) > 25 (BMI > 23 in Asians), hypertension, diabetes mellitus, dyslipidemia, and hypertriglyceridemia. NHANES participants with positive hepatitis B surface antigen, hepatitis C antibody, or hepatitis C RNA were excluded from the study.¹

Investigators defined MetALD as MASLD with increased alcohol intake (3–6 standard drinks per day in males; 2–5 standard drinks per day in females). Individuals with significant alcohol consumption, defined as alcohol-related liver disease (> 6 drinks per day in males and > 5 drinks per day in females), were excluded from the study.¹

In addition to baseline characteristics, investigators also collected information on the outcomes of MASLD and MetALD, including all-cause mortality, cardiovascular mortality, cancer-related mortality, and other causes of mortality, obtained by linking NHANES data to death certificates from the National Death Index based on ICD codes.¹

Of the 5395 individuals included in the study, 2838 (52.60%) had MASLD and 2557 (47.40%) had MetALD. The majority (56.87%) of participants were male and non-Hispanic White (40.74%) with a median age of 50 (Interquartile range [IQR], 36–62) years. Investigators noted participants with MASLD were older (55 vs 45; P <.01), and had a higher prevalence of metabolic components, including hypertension (66% vs 57.25%; P <.01), dyslipidemia (63.64% vs 55.92%; P <.01), hypertriglyceridemia (70.40% vs 63.71%; P <.01), insulin resistance (94.36% vs 91.67%; P <.01), and diabetes mellitus (53.84% vs 46.16%; P <.01) than those with MetALD.¹

During a median follow-up of 56 (IQR, 34–81) months, 253 patients died, including 149 with MASLD and 94 with MetALD. The incidence per 1000 person-years for each type of mortality was:

• 11.21 vs 7.61 (P <.01) for all-cause mortality
• 3.69 vs 1.94 (P <.01) for cardiovascular mortality
• 2.93 vs 1.86 (P = .08) for cancer-related mortality
• 4.59 vs 3.81 (P = .34) for other causes of mortality

In multivariable logistic regression analysis adjusting for age, sex, race, BMI status, smoking status, hypertension, hyperlipidemia, insulin resistance, and FIB-4 score, patients with MetALD had significantly increased cancer-related mortality compared to patients with MASLD (Hazard ratio [HR], 1.32; 95% CI, 1.14–1.53; P <.01). Investigators noted there were no significant differences between all-cause mortality (HR, 1.21; 95% CI, 0.91–1.61; P = .19), CVD (HR, 1.09; 95% CI, 0.52–2.30; P = .83), and other causes of mortality (HR, 1.27; 95% CI, 0.89–1.81; P = .19).¹

Investigators acknowledged multiple limitations to these findings, including the use of noninvasive measures to define steatosis potentially leading to the overestimation or underestimation of its prevalence; the reliance on self-reported alcohol intake to define MetALD; the use of ICD codes to determine CVD and metabolic diseases; the limited number of deaths in the study; the inability to determine which type of cancer caused greater rates of cancer mortality; the lack of data on liver-related mortality; and the potential lack of generalizability to other countries or ethnic groups that are not adequately represented in the NHANES dataset.¹

“Further studies are warranted to understand the pathophysiology of MASLD and the effect of moderate alcohol consumption on disease progression,” investigators concluded.¹ “Close attention to regular cancer surveillance and accurate classification of alcohol consumption in individuals with diagnosed MASLD is warranted to help improve patient care and outcomes.”

References

1. ^{Aboona MB, Danpanichkul P, Chen VL, et al. Mortality outcomes in individuals with MASLD versus MASLD and increased alcohol intake. Journal of Gastroenterology and Hepatology. https://doi.org/10.1111/jgh.16726}
2. ^{Loomba R, Wong VW. Implications of the new nomenclature of steatotic liver disease and definition of metabolic dysfunction-associated steatotic liver disease. Aliment Pharmacol Ther. 2024;59(2):150-156. doi:10.1111/apt.17846}