The Serum Endothelın-1 Level in Steatosıs and NASH, and Its Relatıon wıth Severıty of Lıver Fıbrosıs

Abstract

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.

Clinical Predictors of Different Grades of Nonalcoholic Fatty Liver Disease

“…), which limit their use [10][11][12][13]. Fibroscan has been recently introduced as a noninvasive method for diagnosing liver fibrosis in patients with nonalcoholic fatty liver, but more studies are needed to validate its usefulness [14].…”

MicroRNAs: Small but amazing, and their association with endothelin

“…4), since Bala et al (2010) have found two predicted target sites in SMAD2 3′UTR. In non-alcoholic steatohepatitis (NASH) patients, where fat accumulation leads to inflammation and subsequent fibrosis, Degertekin et al (2007) observed that the serum ET-1 level showed a statistically significant increase as fibrosis severity increased. This ET-1 increase could well be mediated by the difference in expression of hepatic miRNAs such as miRNA 155, as was observed in a mouse model of dietary, non-alcoholic steatohepatitis (Pogribny et al, 2010).…”

“…4). It could be identified in the liver (Yeligar et al, 2009;Degertekin et al, 2007), lung (Crestani, 2007;Jain et al, 2007) and kidney (Oba et al, 2010) as well as in tumors, such as ovarian cancer (Bagnato and Rosano, 2007;Rosano et al, 2011;Vergara et al, 2009). Epithelial-mesenchymal transition (EMT) is a prime example of a reversible differentiation process that occurs during normal development, such as neural tube and mesoderm formation during embryogenesis [Type I EMT, (Carew et al, 2011)].…”

“…In a rat model of liver damage by ethanol-feeding, Yeligar et al (2009) demonstrated that miRNA 199 plays a major role as a negative regulator to control transcription and homeostatic levels of ET-1, leading to a controlled microcirculatory tone. In non-alcoholic liver steatohepatitis (NASH), ET-1 levels have been found to be upregulated in the serum of NASH patients (Degertekin et al, 2007). In a respective murine model, upregulation of miRNA 200b has been observed, among others, indicating that the severity and susceptibility of NASH may be determined by variations in miRNA expression response.…”

Cribado de la enfermedad hepática por depósito de grasa: cómo y a quién

“…Asimismo, se han relacionado con la fibrosis, la HTA, la hiperferritinemia, una marcada hipertrigliceridemia, la historia familiar de EHNA o de cirrosis criptogenética, la obesidad central, un IMC superior a 31 y un cociente HOMA/adiponectinemia elevado 47,48 . Los niveles séricos de endotelina-1 también se relacionan con el grado de fibrosis 50 . Por otro lado, la fibrosis hepática se puede predecir mediante la estimación de parámetros directamente relacionados con la fibrogéne-sis, solos o en combinación.…”