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Background There are conflicting results regarding the association between chronic liver disease (CLD) and depression and the underlying biological mechanisms are lack of investigation. To address the impact of depression and its effects on the management of CLD, its biological marker is critical to be identified. The present study explored the association between serum albumin and depression in CLD patients and whether the association varied in different liver histological stages. Methods Based on the United States National Health and Nutrition Examination Survey 2017–2018, the data of serum albumin and depressive symptoms from 627 participants with CLD were used. Depression symptoms were assessed with the nine-item Patient Health Questionnaire (PHQ-9). We used multivariate linear regression to evaluate the association between serum albumin and PHQ-9 scores. Stratified analysis was performed according to the liver histology examined by vibration controlled transient elastography. Results Serum albumin level was inversely associated with PHQ-9 scores in the multivariate regression model after adjusting for mainly potential confounders (β = − 1.113, 95% CI: − 2.065 to − 0.162,  P  = 0.0221). In the subgroup analysis stratified by gender, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), the inverse association remained significant in female (β = − 2.002, 95% CI: − 3.515 to − 0.489,  P  = 0.0100), patients with CAP &lt; 274 dB/m (β = − 2.215, 95% CI: − 3.621 to − 0.808,  P  = 0.0023) and patients with LSM ≥8.2 kPa (β = − 4.074, 95% CI: − 6.237 to − 1.911,  P  = 0.0003). Moreover, the association was much stronger when the serum albumin was higher than 3.4 g/dL among patients with LSM ≥8.2 kPa (β = − 4.835, 95% CI: − 7.137 to − 2.533,  P  &lt; 0.0001). Conclusion Our study revealed an inverse association between serum albumin and depression in CLD patients and this association differed according to liver histological changes. Serum albumin could be a warning marker for depressive symptoms in CLD patients. It is essential for taking corresponding intervention strategies.

The association between serum albumin and depression in chronic liver disease may differ by liver histology