title: Changes in biomarkers of liver disease during successful combination antiretroviral therapy in HIV-HCV-coinfected individuals.
abstract: BACKGROUND
  We investigated changes in biomarkers of liver disease in HIV-HCV-coinfected individuals during successful combination antiretroviral therapy (cART) compared to changes in biomarker levels during untreated HIV infection and to HIV-monoinfected individuals.
  
  
  METHODS
  Non-invasive biomarkers of liver disease (hyaluronic acid [HYA], aspartate aminotransferase-to-platelet ratio index [APRI], Fibrosis-4 [FIB-4] index and cytokeratin-18 [CK-18]) were correlated with liver histology in 49 HIV-HCV-coinfected patients. Changes in biomarkers over time were then assessed longitudinally in HIV-HCV-coinfected patients during successful cART (n=58), during untreated HIV-infection (n=59), and in HIV-monoinfected individuals (n=17). The median follow-up time was 3.4 years on cART. All analyses were conducted before starting HCV treatment.
  
  
  RESULTS
  Non-invasive biomarkers of liver disease correlated significantly with the histological METAVIR stage (P<0.002 for all comparisons). The mean ±sd area under the receiver operating characteristic (AUROC) curve values for advanced fibrosis (≥F3 METAVIR) for HYA, APRI, FIB-4 and CK-18 were 0.86 ±0.05, 0.84 ±0.08, 0.80 ±0.09 and 0.81 ±0.07, respectively. HYA, APRI and CK-18 levels were higher in HIV-HCV-coinfected compared to HIV-monoinfected patients (P<0.01). In the first year on cART, APRI and FIB-4 scores decreased (-35% and -33%, respectively; P=0.1), mainly due to the reversion of HIV-induced thrombocytopaenia, whereas HYA and CK-18 levels remained unchanged. During long-term cART, there were only small changes (<5%) in median biomarker levels. Median biomarker levels changed <3% during untreated HIV-infection. Overall, 3 patients died from end-stage liver disease, and 10 from other causes.
  
  
  CONCLUSIONS
  Biomarkers of liver disease highly correlated with fibrosis in HIV-HCV-coinfected individuals and did not change significantly during successful cART. These findings suggest a slower than expected liver disease progression in many HIV-HCV-coinfected individuals, at least during successful cART.
authors.affiliation: Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland.
authors.forename: Janine
authors.initials: J
authors.lastname: Rohrbach
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Patrick
authors.initials: P
authors.lastname: Schmid
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thormann
authors.forename: Helen
authors.initials: H
authors.lastname: Kovari
authors.forename: Alexandra
authors.initials: A
authors.lastname: Scherrer
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Danielle
authors.initials: D
authors.lastname: Vuichard
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Juan
authors.initials: J
authors.lastname: Ambrosioni
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood*; D060085:Coinfection; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers