Evaluation of oxidative stress impact on Non-alcoholic faty liver disease and Non-alcoholic steatohepatitis

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver without excessive alcohol intake in association with Type-2 Diabetes and obesity. Non-alcoholic steatohepatitis (NASH) is the advanced and severe form of NAFLD and defined by the presence of inflamattion, injury and apoptosis in hepatocytes. While the prognosis of simple steatosis is favorable, NASH may progress to cirrhosis and hepatocellular carcinoma. The mechanisms that cause NAFLD are still unclear. In a multiple- parallel-hit model, various factors play a role in the pathophysiology of NAFLD and these include; genetic polymorphism, epigenetic alterations, insulin resistance, diet, lack of physical activity, obesity, dysregulation of adipokines, lipotoxicity, oxidative stress, disruption of the intestinal flora and endocrine disorders. Additional etiological factors except that fat accumulation are usually present in the development of NASH. Many studies have shown that oxidative stress is piovital in the progression of NAFLD to NASH. This study aimed to evaluate oxidants and antioxidants in simple steatosis and NASH and the role of oxidative stress in the progression of NAFLD to NASH. MATERIALS AND METHODS: A total of 99 patients diagnosed steatosis with ultrasonography were enrolled in the study. The patients were divided into two groups; 49 patients with normal serum ALT were in NAFLD group and 50 patients with high serum ALT were in NASH group. According the level of increase in echogenicity in ultrasonography, patients were classifed into three groups as Grade 1, Grade 2 and Grade 3. The biochemical parameters and Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Malondialdehyde (MDA) were measured. Height and weight measurements of all patients were done and body mass index (BMI) was calculated using the formula weight/square meters. Oxidative Stress Index (OSI) was calculated using the formula TOS/TAS. The study data was statistically analyzed using SPSS 20.0 programme. Chi-square test was used to evaluate the distribution of categorical data between groups. Normality and homogeneity of numerical data were analyzed using Kolmogorov-Smirnov and Levene's tests. Mann Whitney U test was used in comparison of numerical data between groups and T test was used in independent sampling. In addition, Pearson and Spearman' s tests were used to analyze the correlation of two variables. The %95 level of confidence interval (p=0,05) was applied to evaluate all data. A value of p<0,05 was considered statistically significant. RESULTS: In statistical analyses TAS, TOS levels and OSI were significantly higher in the NASH group compared to the NAFLD group (p<0,05). MDA levels were higher in the NASH group than the NAFLD group, but there was no significant difference between groups (p=0,418). TAS and MDA levels increased as the severity of liver fat increased and were statistically significant (p<0,05). Altough TOS levels increased as the severity of liver fat increased, there was no significant difference (p=0,083). As the triglyceride and ALT levels and BMI measures increased, the degree of liver fat increased and were statistically significant (p<0,05). Positive correlation was found between MDA and triglyceride levels (r=0,493) (p<0,05). The patients in the NASH group had significant higher levels of AST, ALT, GGT, ALP, triglyceride and fasting blood glucose compared to the NAFLD group (p<0,05). CONCLUCIONS: Because oxidative stress has a key role in the development of NASH, treatments aimed to reduce oxidative stress may contribute to prevent or slowdown the progression of NAFLD to NASH.