title: Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.
abstract: MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed.
authors.affiliation: Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Doris Duke Foundation, New York, New York.
authors.forename: Perry H
authors.initials: PH
authors.lastname: Dubin
authors.forename: Hejun
authors.initials: H
authors.lastname: Yuan
authors.forename: Robert K
authors.initials: RK
authors.lastname: Devine
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hynan
authors.forename: Mamta K
authors.initials: MK
authors.lastname: Jain
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000473:pathology; D006801:Humans; D017114:Liver Failure, Acute / Q000097:blood*; D035683:MicroRNAs / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D000410:Alanine Transaminase
keywords: HCV; acetaminophen; biomarker; liver injury; micro-RNA