Bidirectional association between zinc and liver cirrhosis: evidence from mendelian randomization and clinical validation.

BACKGROUND

It remains unclear whether low blood zinc levels in cirrhosis patients are a cause or a consequence of the disease.

METHODS

Seven blood metals (calcium, iron, magnesium, phosphorus, copper, selenium, zinc) were assessed using two-sample Mendelian randomization (MR). We performed reverse MR analysis on the positive results and subsequently evaluated the zinc findings in a cohort of 137 cirrhosis patients.

RESULTS

MR analysis revealed that higher genetically predicted zinc levels were associated with an increased cirrhosis risk (OR = 1.24, 95% CI = [1.04, 1.46], p = 0.014). No significant associations were found for other metals. Reverse MR analysis revealed no reverse causality between liver cirrhosis and zinc. In the clinical cohort, 60.5% of patients had hypozincemia, and zinc levels declined progressively with worsening Child-Pugh score (r = - 0.615, p < 0.01). Additionally, a positive correlation was observed between serum zinc levels and albumin (ALB). In contrast, zinc levels were inversely associated with total bilirubin (TBIL), prothrombin time (PT), and international normalized ratio (INR).

CONCLUSION

Genetically higher zinc levels predispose individuals to cirrhosis, whereas advanced cirrhosis induces zinc deficiency. These bidirectional findings suggest that zinc exerts opposite effects at different disease stages.