Serum melatonin predicts hepatic encephalopathy in patients with liver cirrhosis

Hepatic encephalopathy (HE) is a serious complication in patients with liver cirrhosis and is strongly associated with morbidity and mortality. Melatonin, a neuroprotective hormone secreted by the pineal gland and enterochromaffin cells of the gastrointestinal tract is involved in the sleep cycle in normal people. This may be disrupted in cirrhotic patients. We aimed at evaluating the role of serum melatonin in cirrhotic patients with HE.

A prospective observational study was conducted in hospitalized patients with liver cirrhosis after meeting the inclusion and exclusion criteria. Morning melatonin levels were measured in patients categorized into three groups based on their progression of HE according to West Haven criteria (WHC) as group 1 (no HE), group 2 (WHC grades I and II) and group 3 (WHC grades III and IV). Biochemical measurements were done using standardized procedures.

Fifty-two patients underwent morning melatonin levels, with a mean age of 55.46 ± 12.26 years old, and nine (17.3%) patients were women. The morning melatonin levels (pg/mL) of healthy volunteers and liver cirrhosis patients were 23.88 (range, 12.54-31.32) and 190 (range, 30.53-300) pg/mL. Among cirrhotic patients, group 1 (n = 11), group 2 (n = 27) and group 3 (n = 14), the morning melatonin levels were (pg/mL) 45.62 ± 15.09, 214.01 ± 107.78 and 280.98 ± 52.74 (p < 0.001), respectively. The correlation coefficient (r) between morning melatonin levels and the grades of HE was 0.797 (p < 0.001). A serum melatonin level of ≥ 85 pg/mL predicted HE with a sensitivity of 86.96%, specificity of 100%, positive predictive value of 100%, negative predictive value of 71.43% and accuracy of 90.16%. The area under the receiver operating characteristic curve (AUROC) for melatonin in predicting HE was 0.94 (p < 0.001).

Serum melatonin levels are significantly higher in HE patients with liver cirrhosis, with the highest levels measured in patients with the most severe grade of HE. A melatonin level of ≥ 85 pg/mL was associated with HE and level ≥ 248.95 pg/mL was associated with severe HE. Prospective large studies are required to validate the role of melatonin as a prognostic marker.