Clinical Significance of Marginal Zinc Deficiency as a Predictor of Covert Hepatic Encephalopathy in Patients with Liver Cirrhosis

Int J Mol Sci. 2025 Apr 28;26(9):4184. doi: 10.3390/ijms26094184.

Abstract

Covert hepatic encephalopathy (CHE) can worsen the quality of life and prognosis of patients with cirrhosis. We analyzed the risk factors of CHE and identified patients at high risk for overt hepatic encephalopathy (HE) who would benefit from therapeutic interventions. We included 145 patients without a history of or treatment for overt HE. Patients were divided into the CHE and no-CHE groups (n = 91 and 54, respectively). CHE had a score above the age-based cutoff value of one of the neuropsychological tests, such as the Stroop and number connection tests. CHE prevalence was 62.8% (n = 91). Compared with the no-CHE group, the CHE group had significantly lower serum zinc and albumin levels. Multiple logistic regression analysis identified serum zinc levels at a cutoff value of 74 µg/dL. Subclinical zinc deficiency showed a diagnostic performance of 55.6% sensitivity and 81.5% specificity for CHE. Blood ammonia levels and liver functional reserves were not predictive of CHE. Compared with patients with zinc levels < 74 µg/dL (n = 102), those with ≥74 µg/dL (n = 43) had significantly lower CHE prevalence and better hepatic functional reserve. Subclinical zinc deficiency was associated with CHE occurrence in patients with cirrhosis without a history of or treatment for overt HE. Measurement of zinc levels facilitates early detection of CHE by neuropsychological testing.

Keywords: covert hepatic encephalopathy; neuropsychological test; zinc.

MeSH terms

  • Adult
  • Aged
  • Clinical Relevance
  • Female
  • Hepatic Encephalopathy* / blood
  • Hepatic Encephalopathy* / diagnosis
  • Hepatic Encephalopathy* / epidemiology
  • Hepatic Encephalopathy* / etiology
  • Humans
  • Liver Cirrhosis* / blood
  • Liver Cirrhosis* / complications
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Prognosis
  • Risk Factors
  • Zinc* / blood
  • Zinc* / deficiency

Substances

  • Zinc