mi R-122 negatively correlates with liver fibrosis as detected by histology and FibroScan

AIM: To investigate whether expression of selected mi RNAs obtained from fibrotic liver biopsies correlate with fibrosis stage.METHODS: Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections(types B, C), 19 with autoimmune liver diseases(autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology(alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNAisolation, expression levels of mi R-21, mi R-122, mi R-214, mi R-221, mi R-222, and mi R-224 were determined using Taq Man Micro RNA Assays applying mi R-140 as the reference. Selection of mi RNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of mi RNAs was correlated with fibrosis stage and liver stiffness(LS) value measured by transient elastography, as well as with serum alanine aminotransferase(ALT) level.RESULTS: The expression of individual mi RNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of mi R-122 in stage F4 was statistically significant(P < 0.04). When analyzing mi RNA expression in relation to fibrosis, levels of mi R-122 and mi R-221 showed negative correlations with fibrosis stage, and mi R-122 was found to correlate negatively and mi R-224 positively with LS values(all P < 0.05). ALT levels displayed a positive correlation with mi R-21(P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between mi R-122 and fibrosis stage and LS values(P < 0.05), and in the samples of chronic viral hepatitis, between mi R-221 and fibrosis stage(P < 0.01), whereas mi R-21 showed positive correlation with ALT values in the samples of autoimmune liver diseases(P < 0.03). The results also revealed a strong correlation between fibrosis stage and LS values(P < 0.01) when etiology of fibrosis was not taken into account.CONCLUSION: Reduced expression of mi R-122 in advanced fibrosis and its correlation with fibrosis stage and LS values seem to be characteristic of hepatic fibrosis of various etiologies.

Elevated miR-33a and miR-224 in steatotic chronic hepatitis Cliver biopsies

AIM:To assess the expression of selected microRNAs(miRNA) in hepatitis C,steatotic hepatitis C,noninfected steatotic and normal liver tissues.METHODS:The relative expression levels of miR-21,miR-33 a,miR-96,miR-122,miR-125 b,miR-221 and miR-224 were determined in 76 RNA samples isolated from 18 non-steatotic and 28 steatotic chronic hepatitis C(CHC and CHC-Steatosis,respectively) cases,18 non-infected,steatotic liver biopsies of metabolic origin(Steatosis) and 12 normal formalin-fixed paraffin-embedded liver tissues using TaqMan MicroRNA Assays.All CHC biopsy samples were obtained prior to initiating therapy.Patients' serum biochemical values,which included glucose,triglyceride,cholesterol,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl-transferase(GGT),alkaline phosphatase(AP),were obtained and correlated with relative miRNA expression.RESULTS:When compared with control non-infected liver samples,miR-122 and miR-221 levels were reduced in CHC-Steatosis(P < 0.03) and in CHC,CHCSteatosis and Steatosis(P < 0.01).Alternatively,the expression of miR-33 a and miR-224 were elevated in CHC-Steatosis and Steatosis in comparison to control tissue(P < 0.01).The levels of miR-33 a and miR-224 in CHC-Steatosis(P < 0.02) and miR-224 in Steatosis(P < 0.001) were increased in comparison to CHC samples.By contrast,the expression of miR-21 did not differ statistically between diseased and normal liver samples.Levels of miR-33 a correlated negatively with serum AST and AP levels in Steatosis as well as with necroinflammatory grade in CHC,whereas miR-21 correlated positively with AST in Steatosis and displayed negative correlation with triglyceride level in CHC-Steatosis.In contrast,miRNA levels were not correlated with ALT,GGT,cholesterol levels or fibrosis stage.CONCLUSION:Differences in miRNA expression were observed between CHC and steatotic CHC,CHC and steatotic liver,but not between steatotic CHC and steatotic liver of metabolic origin.