Micro RNAs mir-106a, mir-122 and mir-197 are increased in severe acute viral hepatitis with coagulopathy.
OBJECTIVE
The severity of acute viral hepatitis, which may be caused by several distinct viruses, varies among individual patients. In rare cases, severe hepatic injury with sudden loss of liver function may occur, which is clinically indicated by the occurrence of coagulopathy or encephalopathy. As the molecular mechanisms of this liver injury are largely unknown, we investigated extracellular micro RNA (miRNA) profiles in 54 patients acutely infected with one of four different hepatotropic viruses, in order to identify those miRNAs which indicate severe viral hepatitis associated with coagulopathy.


METHODS
First, the profile of miRNAs was extensively analysed using a microarray-based approach in highly characterized 24 patients, matched in terms of sex, age and level of liver enzymes, as well as in three healthy controls. The cohort included samples from 18 patients with moderate and six individuals with severe hepatitis, indicated by abnormal prothrombin time and higher alanine aminotransferase and bilirubin levels. miRNAs found to be upregulated in severe hepatitis were then quantified by real-time PCR in the expanded cohort of 54 patients.


RESULTS
Comprehensive microarray-based miRNA profiling identified upregulation of mir-106a, mir-122 and mir-197 in patients with severe acute viral hepatitis with coagulopathy, as compared to patients who did not develop coagulopathy. mir-106a, mir-122 and mir-197 were then proven to be significantly upregulated in patients with severe acute viral hepatitis by quantitative real-time PCR (P < 0.01, Mann-Whitney U-test).


CONCLUSIONS
mir-106a, mir-122 and mir-197 could be potential markers for severe acute viral hepatitis associated with coagulopathy.
Department of Virology, Medical University of Vienna, Vienna, Austria.
Lukas
L
Weseslindtner
Institute for Pathology, University Hospital of Cologne, Cologne, Germany.
Iris
I
Macheleidt
Institute for Pathology, University Hospital of Cologne, Cologne, Germany.
Hannah
H
Eischeid
Division of Clinical Virology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Robert
R
Strassl
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Harald
H
Hofer
Division of Clinical Virology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Theresia
T
Popow-Kraupp
Institute of Pathology, Medical University of Vienna, Vienna, Austria.
Hans-Peter
HP
Dienes
Department of Virology, Medical University of Vienna, Vienna, Austria.
Heidemarie
H
Holzmann
Institute for Pathology, University Hospital of Cologne, Cologne, Germany.
Margarete
M
Odenthal
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006506:Hepatitis A / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006509:Hepatitis B / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006526:Hepatitis C / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016751:Hepatitis E / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011517:Prothrombin Time; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015854:Up-Regulation; D055815:Young Adult
C542541:MIRN106 microRNA, human; C531907:MIRN122 microRNA, human; C546085:MIRN197 microRNA, human; D035683:MicroRNAs
acute hepatitis; micro RNA; mir-106; mir-122; mir-197