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Hepatic encephalopathy (HE), a neuropsychiatric abnormality that commonly accompanies cirrhosis of the liver, is often difficult to treat and manage. Changes in chloride homeostasis are involved in the generation of a number of brain disorders. In this study, we considered whether chloride homeostasis is associated with HE. The mRNA levels of the Cl(-) extrusion system (KCC2) and the Cl(-) intrusion system (NKCC1) were detected by real-time RT-PCR in the plasma of 29 cirrhotic patients with HE of grade I-II, 36 cirrhotic patients with HE of grade III-IV, 20 cirrhotic patients without HE and 15 healthy controls. The mRNA levels of KCC2 in cirrhotic patients with mild and severe HE were significantly lower compared to those in cirrhotic patients without HE or in the healthy controls. However, NKCC1 mRNA levels did not differ between the different groups. In addition, for cirrhotic patients with HE, there were significant negative correlations between KCC2 levels and the levels of blood ammonia and hepatic function scores (Child-Pugh and model for end-stage liver disease scores); there was also a significant positive correlation between KCC2 levels and neurological status (Glasgow scores). In conclusion, our study indicates that an imbalance of KCC2 and NKCC1 may be a novel biomarker for detecting HE and for monitoring disease development.

Changes in expression of the chloride homeostasis-regulating genes, KCC2 and NKCC1, in the blood of cirrhotic patients with hepatic encephalopathy