Systematic Review With Meta-Analysis: Effects Of Statins On The Hepatic Decompensation, Complications, Mortality And Drug Safety In Liver Cirrhosis

Background:The progression of NAFLD is not fully understood, with some patients remaining clinically stable while others progress to NASH.Disease severity has been demonstrated to have a closer correlation with amount of liver fibrosis, indicated by the presence of collagen, independent of staging within NAFLD or NASH.Computerized morphometry (CM) is a semi-quantitative tool which can accurately assess collagen levels in a liver biopsy.Aim: To examine the relationship of percent collagen in the liver as determined by semi quantitative CM with serum cytokine markers of inflammation and fibrosis in obese subjects with a range of NAFLD staging as determined by a single histopathologist (ZG).Cohorts and Methods: Liver and serum samples were obtained from 111 obese patients while undergoing bariatric surgery.Four cohorts based on histopathological diagnosis of no disease (4.5%), mild abnormalities (25.2%),Simple Steatosis (32.4%), and NASH (37.8%) were allocated after exclusion of confounding factors such as alcohol use or HCV.Mean age was 42.6 (+/-11.8)years, BMI of 47.9 (+/-9.0)kg/m 2 , ALT of 33.5 (+/-24.9)U/L, and mean AST of 27.3 (+/-17.5)U/L.Subjects were 72.1% female and 27.9% male.The same liver tissue blocks used for diagnosis were stained with picroSirius red and scanned, then images were manually annotated to exclude artifacts and used to determine % collagen deposition.Sera was analyzed with a 17-plex magnetic bead immunoassay (Bio-Rad).Data was analyzed for significant correlation of cytokines with % collagen as well as significant changes in cytokine levels across cohort groups.Kendall's Tau, Spearman's and Mann-Whitney non parametric tests were done on all variables, statistically significant cutoff of p<0.05 was used.Results: Interestingly the only significant negative correlation was found between percent collagen and both IL-7 (p<0.05) and IFN-g (p<0.05).IL-7 and the hepatocyte growth factor (HGF) is known to form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor.There was no significant change in IL-7 when comparing values between histopathological cohorts.Significant changes were noted for IFN-g levels between cohorts of no disease and mild abnormal (<0.05), no disease and Simple Steatosis (p<0.05), and between Simple Steatosis and NASH cohorts (p<0.05)(Table 1).Conclusion: The negative correlation between % collagen and IL-7 and IFN-g suggest possible involvement in the pathogenesis of fibrosis in NAFLD.Additional studies are needed to clearly determine the exact role of these pathways in collagen deposition in NAFLD.