Micro-RNA-122 levels in acute liver failure and chronic hepatitis C

Perry H. Dubin, Hejun Yuan, Robert K. Devine, Linda S. Hynan, Mamta K. Jain, William M. Lee, Anne M. Larson, Iris Liou, Timothy Davern, Oren Fix, Michael Schilsky, Timothy McCashland, J. Eileen Hay, Natalie Murray, A. Obaid, S. Shaikh, Andres Blei, Daniel Ganger, Atif Zaman, Steven H B HanRobert Fontana, Brendan McGuire, Raymond T. Chung, Alastair Smith, Robert Brown, Jeffrey Crippin, Edwin Harrison, Adrian Reuben, Santiago Munoz, Rajender Reddy, R. Todd Stravitz, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein

Research output: Contribution to journalArticle

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1507-1514
Number of pages8
JournalJournal of Medical Virology
Volume86
Issue number9
DOIs
StatePublished - 2014

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Keywords

  • Acetaminophen
  • Biomarker
  • HCV
  • Liver injury
  • Micro-RNA

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Medicine(all)

Cite this

Dubin, P. H., Yuan, H., Devine, R. K., Hynan, L. S., Jain, M. K., Lee, W. M., Larson, A. M., Liou, I., Davern, T., Fix, O., Schilsky, M., McCashland, T., Hay, J. E., Murray, N., Obaid, A., Shaikh, S., Blei, A., Ganger, D., Zaman, A., ... Hassanein, T. (2014). Micro-RNA-122 levels in acute liver failure and chronic hepatitis C. Journal of Medical Virology, 86(9), 1507-1514. https://doi.org/10.1002/jmv.23987