title: Insulin resistance is associated with a higher risk of hepatocellular carcinoma in cirrhotic HIV/HCV-co-infected patients: results from ANRS CO13 HEPAVIH.
abstract: OBJECTIVE
  Compared to HCV-mono-infected patients, hepatocellular carcinoma (HCC) occurs at younger age in HIV/HCV-co-infected patients, is markedly more advanced at diagnosis, is less amenable to curative treatment, and has a more severe outcome. The aim of this study was to identify factors predictive of HCC occurrence in a large cohort of HIV/HCV-co-infected patients with cirrhosis.
  
  
  METHODS
  This study involved 244 HIV/HCV-co-infected patients included in the ANRS CO13 HEPAVIH cohort, who had HCV-related cirrhosis (clinically or histologically proven cirrhosis, or liver stiffness ≥12.5 kPa) and no signs of HCC at baseline. Cox proportional hazards models were used to identify factors associated with HCC occurrence.
  
  
  RESULTS
  During a median follow-up of 2.6 (IQR, 1.8-3.5) years, 21 patients (8.6%) developed HCC. Diagnosis of HCC was based on histology in 5 patients (24%) and non-invasive criteria in 16 patients (76%). In univariate analyses, the following factors were related to HCC occurrence: age, previous cirrhosis decompensation, a HOMA value >3.8 (patients with treated diabetes were excluded from the HOMA calculation), a lower platelet count, a lower prothrombin level, and higher alpha-fetoprotein levels. The HOMA value was >3.8 at baseline in 66.7% of patients who developed HCC and in 35.3% of the remaining patients (p=0.016). In multivariate analysis, age over 50 years (adjusted RR 3.2, 95% CI 1.2-9.0; p=0.02) and a HOMA value >3.8 (adjusted RR 3.4, 95% CI 1.1-10.3; p=0.03) remained significantly associated with HCC occurrence.
  
  
  CONCLUSIONS
  As in HCV-mono-infected patients with HCV-related cirrhosis, insulin resistance appears to play a key role in HCC occurrence in HCV/HIV-co-infected patients with cirrhosis. This finding calls for specific screening strategies for patients with a particularly high risk of developing HCC.
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.forename: Firouzé
authors.initials: F
authors.lastname: Bani-Sadr
authors.forename: Marc-Arthur
authors.initials: MA
authors.lastname: Loko
authors.forename: Hind
authors.initials: H
authors.lastname: Stitou
authors.forename: Anne
authors.initials: A
authors.lastname: Gervais
authors.forename: Jacques
authors.initials: J
authors.lastname: Durant
authors.forename: Eric
authors.initials: E
authors.lastname: Rosenthal
authors.forename: Yann
authors.initials: Y
authors.lastname: Quertainmont
authors.forename: Karl
authors.initials: K
authors.lastname: Barange
authors.forename: Daniel
authors.initials: D
authors.lastname: Vittecoq
authors.forename: Michka
authors.initials: M
authors.lastname: Shoai-Tehrani
authors.forename: Muriel
authors.initials: M
authors.lastname: Alvarez
authors.forename: Maria
authors.initials: M
authors.lastname: Winnock
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Trinchet
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.forename: Philippe
authors.initials: P
authors.lastname: Sogni
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology*; D006526:Hepatitis C / Q000150:complications* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance / Q000502:physiology*; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012307:Risk Factors