title: Circulating microRNAs as a marker for liver injury in human immunodeficiency virus patients.
abstract: Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in HIV patients with regard to the extent and etiology of liver injury. Total RNA was extracted from 335 serum samples of HIV patients and 22 healthy control participants using Qiazol. Comprehensive polymerase chain reaction (PCR) array analyses (768 miRNA) were performed in serum samples of eight HIV, eight HIV/HCV (hepatitis C virus), six HCV patients, and three healthy controls. Reverse transcription (RT)-PCR measured levels of miRNA-122, miRNA-22, and miRNA-34a in serum samples of 335 patients and 19 healthy control participants. Liver injury and fibrosis in these patients were defined using aspartate aminotransferase (AST) levels, fibrosis-4 (FIB-4) index and AST-to-platelet ratio index (APRI) score. The miRNA pattern of HIV/HCV samples showed altered expression of 57 and 33 miRNA compared to HCV and HIV infection, respectively. miRNA-122, miRNA-22, and miRNA-34a were highly up-regulated in HIV/HCV patients. Analyzing the entire cohort, these miRNAs were correlated with liver function tests and were independent predictors of liver injury (AST >2 × ULN). miRNA-122 and miRNA-22 were associated with relevant fibrosis (FIB-4 >1.45; APRI >1). Circulating levels of miRNA-122 were independent predictors for relevant fibrosis in HIV patients. Interestingly, miRNA-122 and miRNA-34a levels were higher in HIV/HCV patients, miRNA-22 levels were highest in HIV/HBV patients, and circulating levels of miRNA-34a correlated positively with illicit drug use and ethanol consumption.
  
  
  CONCLUSIONS
  Circulating miRNA-122, miRNA-22, and miRNA-34a correlates with the etiology of liver injury in HIV patients. These biomarkers not only mirror different mechanisms of hepatic injury, but also are independent predictors of liver injury in HIV patients.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Evrim
authors.initials: E
authors.lastname: Anadol
authors.forename: Robert
authors.initials: R
authors.lastname: Schierwagen
authors.forename: Natalia
authors.initials: N
authors.lastname: Elfimova
authors.forename: Katharina
authors.initials: K
authors.lastname: Tack
authors.forename: Carolynne
authors.initials: C
authors.lastname: Schwarze-Zander
authors.forename: Hanna
authors.initials: H
authors.lastname: Eischeid
authors.forename: Andrea
authors.initials: A
authors.lastname: Noetel
authors.forename: Christoph
authors.initials: C
authors.lastname: Boesecke
authors.forename: Christian
authors.initials: C
authors.lastname: Jansen
authors.forename: Leona
authors.initials: L
authors.lastname: Dold
authors.forename: Jan-Christian
authors.initials: JC
authors.lastname: Wasmuth
authors.forename: Christian P
authors.initials: CP
authors.lastname: Strassburg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Jürgen Kurt
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Margarete
authors.initials: M
authors.lastname: Odenthal
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D060085:Coinfection / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications*; D064368:Healthy Volunteers; D048550:Hepatic Insufficiency / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D006525:Hepatitis, Viral, Human / Q000097:blood / Q000150:complications* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs