Chronotypology and melatonin alterations in minimal hepatic encephalopathy

BACKGROUND: "Minimal (subclinical) hepatic encephalopathy" is a term that describes impairment of every day life activities in cirrhosis patients without clinical neurologic abnormalities. Melatonin diurnal pattern disruption and metabolic changes due to liver insufficiency can affect the human biologic clock. Our study was conducted to measure plasma melatonin levels in an attempt to correlate plasma melatonin abnormalities with liver insufficiency severity, and describe chronotypology in cirrhosis patients with minimal encephalopathy. METHODS: Twenty-six cirrhotic patients enrolled in the study and thirteen patients without liver or central nervous system disease served as controls. All patients had full clinical and biochemical evaluation, chronotypology analysis, neurological evaluation, melatonin profile and quality of life assessment. RESULTS: Cirrhotic patients with minimal encephalopathy exhibit melatonin secretion abnormalities. Cirrhosis patients with more severe hepatic insufficiency (Child-Pugh score > 5) had significantly (p < 0.04) lower evening melatonin levels compared to patients with less severe insufficiency (Child-Pugh score = 5). Chronotypology analysis revealed Morning Type pattern in 88% of cirrhosis patients. DISCUSSION: The presence of abnormal plasma melatonin levels before the onset of clinical hepatic encephalopathy, and the finding that patients with more severe cirrhosis have lower evening melatonin levels are the most important findings of this study. Despite these melatonin abnormalities, chronotypology revealed Morning Type pattern in 23 of 26 cirrhosis patients. We believe these findings are important and deserve further study. CONCLUSION: Melatonin abnormalities occur in cirrhosis patients without clinical encephalopathy, are related to liver insufficiency severity, may influence chronotypology patterns, and certainly deserve further investigation.