PubMed ID:
24895202
Public Release Type:
Journal
Publication Year: 2014
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.
DOI:
https://doi.org/10.1002/jmv.23987
Authors:
Chung RT,
Durkalski V,
Lee WM,
Lee WM,
Acute Liver Failure Study Group,
Attar N,
Battenhouse H,
Blei A,
Brown R,
Crippin J,
Davern T,
Devine RK,
Dillon C,
Dubin PH,
Fix O,
Fontana R,
Ganger D,
Goddard T,
Han SH,
Harrison E,
Hassanein T,
Hay J,
Hynan LS,
Hynan LS,
Jain MK,
Lalani E,
Larson AM,
Liou I,
McCashland T,
McGuire B,
Munoz S,
Murray N,
Pezzia C,
Reddy R,
Reuben A,
Rossaro L,
Samuel G,
Sanders C,
Satyanarayana R,
Schilsky M,
Shaikh A,
Smith A,
Stravitz R,
Yuan H,
Zaman A,
Zhao W
Studies:
Acute Liver Failure Study Group: Adult Acute Liver Failure Study
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.