The serum endothelin-1 level in steatosis and NASH, and its relation with severity of liver fibrosis.

Endothelin-1 (ET-1) is known to play an important role in hepatic fibrosis. ET-1 is also a mediator that is elevated in conditions such as insulin resistance, hyperglycemia, oxidative stress, and endothelial cell dysfunction. In this study, we investigated whether ET-1 has a role in determining the severity of liver fibrosis in NASH. Also, the relation between ALT levels, obesity, diabetes, and AST/ALT ratio and fibrosis and ET-1 level was sought. A total of 92 patients were enrolled in the study. The patients were categorized into three groups: group 1, patients with elevated transaminase levels who were diagnosed as NASH by liver biopsy (n=40); group II, patients with only hepatosteatosis determined by biopsy but having elevated transaminase levels (n=12); and group III, patients with hepatosteatosis observed by ultrasonography, having normal transaminase levels (n=40). The serum ET-1 level was measured by an appropriate ELISA kit for all patients. Mean serum ET-1 level was statistically significantly higher in the NASH group compared to the other two groups (15.56+/-4.63 vs 6.75+/-2.46 and 5.74+/-2.34 micromol/L; P < 0.01). Mean serum ET-1 levels in NASH patients with grade I, grade II, and grade IV fibrosis were 14.06+/-0.92, 17.70+/-2.32, and 20.40+/-1.40 micromol/L, respectively. None of the patients were identified as grade III fibrosis. It was found that the serum ET-1 level showed a statistically significant increase as fibrosis severity increased in NASH patients (P < 0.05). In conclusion, the serum ET-1 level is higher in NASH patients compared to patients having only steatosis. There appears to be a correlation between severity of fibrosis and serum ET-1 level in NASH patients. It has been found that NASH patients having a twofold increase in their ALT levels had higher ET-1 levels and a more severe grade of fibrosis.