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, hyper-glycemia, 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 levelwas 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 mu mol/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 mu mol/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.