Introduction

Updated nomenclature for steatotic liver disease (SLD) uses moderate-to-heavy alcohol drinking to classify metabolic dysfunction-associated steatotic liver disease (MASLD) and with increased alcohol intake (MetALD). However, the association between light-to-moderate alcohol drinking (≤14 g/d for females and ≤28 g/d for males) and the risk of SLD, particularly MASLD, remains unclear, with this knowledge gap being especially pronounced in Chinese populations where prospective cohort evidence remains scarce. In this study, we conducted a cohort study of 2942 Chinese adult participants using data from the Anhui Liver Disease Study (ALDS), where SLD and its subtypes were defined based on vibration-controlled transient elastography (VCTE).We examined the relationship between light-to-moderate alcohol drinking and the risk of SLD and MASLD.We further investigated gut microbiome changes linked to light-to-moderate drinking, and assessed the association between light-to-moderate alcohol-associated microbiota and SLD in a subset of the ALDS.

Aims & Methods

We aimed to investigate the association between light-to-moderate drinking and the risk of incident SLD/MASLD, assess the 1-year gut microbiome changes linked to light-to-moderate drinking, and examine the association between light-to-moderate alcohol-associated microbiota and SLD.In a cohort of 2942 Chinese adults from the Anhui Liver Disease Study (ALDS), alcohol intake was measured via a validated food frequency questionnaire, while SLD were diagnosed by vibration-controlled transient elastography. In a subset of ALDS (n=330), dietary information and fecal samples for 16S rRNA sequencing were collected twice, 1 year apart. Cox regression and logistic regression were used to calculate multivariable-adjusted hazard ratios (aHRs) and odds ratios (aORs) with 95%CIs, respectively.

Results

Upon 4 years of follow-up, 513 SLD (473 MASLD) were newly identified among participants without pre-existing SLD. Light-to-moderate alcohol drinkers exhibited higher risks of SLD (aHR=1.27, 95%CI: 1.03-1.58) and MASLD (aHR=1.27, 95%CI: 1.01-1.59) versus abstainers. Such positive association persisted in subgroups by age, sex, the number of cardiometabolic risk factors, physical activity, and diet quality. Beverage-specific analysis revealed positive associations with SLD risk for liquor (aHR=1.29, 95%CI:1.01-1.65) and beer (aHR=1.38, 95%CI: 0.96-1.99), but not wine. Longitudinal microbiome analysis identified 16 genera with altered abundance in light-to-moderate alcohol drinkers: 8 increased (including Actinomyces) and 8 decreased (all P_FDR<0.05). Among these genera, Actinomyces abundance correlated with SLD risk (aOR=1.19, 95%CI: 1.03-1.41).

Conclusion

Our findings support that light-to-moderate alcohol drinking was associated with higher risks of SLD and MASLD, which might be partly via modulation of gut microbial composition.

References

[1] Israelsen M, Francque S, Tsochatzis EA, Krag A. Steatotic liver disease. Lancet. 2024;404(10464):1761-78. https://doi.org/10.1016/S0140-6736(24)01811-7.
[2] Younossi ZM, Stepanova M, Ong J, Trimble G, AlQahtani S, Younossi I, Ahmed A, Racila A, Henry L. Nonalcoholic Steatohepatitis Is the Most Rapidly Increasing Indication for Liver Transplantation in the United States. Clin Gastroenterol Hepatol. 2021;19(3):580-9 e5. https://doi.org/10.1016/j.cgh.2020.05.064.
[3] Wong VWS, Ratziu V, Bugianesi E, Francque S, Zelber-Sagi S, Valenti L, Roden M, Schick F, Yki-Järvinen H, Gastaldelli A, Vettor R, Frühbeck G, Dicker D, Easl, Easl, Easd, Easo. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81(3):492-542. https://doi.org/10.1016/j.jhep.2024.04.031.
[4] Mak LY, Liu K, Chirapongsathorn S, Yew KC, Tamaki N, Rajaram RB, Panlilio MT, Lui R, Lee HW, Lai JC, Kulkarni AV, Premkumar M, Lesmana CRA, Hsu YC, Huang DQ. Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions. Nat Rev Gastroenterol Hepatol. 2024;21(12):834-51. https://doi.org/10.1038/s41575-024-00967-4.