title: Liver fibrosis regression and progression during controlled hepatitis B virus infection among HIV-HBV patients treated with tenofovir disoproxil fumarate in France: a prospective cohort study.
abstract: Long-term tenofovir disoproxil fumarate (TDF) use has been associated with significant regression of liver fibrosis during hepatitis B virus (HBV) mono-infection, yet little is known during HIV-HBV coinfection. The aim of this study was to evaluate the evolution of liver fibrosis and its determinants in TDF-treated coinfected patients.
  
  
  
  In this prospective cohort study, 167 HIV-HBV-infected patients initiating TDF-containing antiretroviral therapy were included. Fibrosis was assessed using the FibroTest® at baseline and every six to twelve months. Risk factors for fibrosis progression (F0-F1-F2 to F3-F4) and regression (F3-F4 to F0-F1-F2) were evaluated.
  
  
  
  At baseline, 134 (80.2%) patients had detectable HBV-DNA (median = 4.93 log10IU/mL, IQR = 2.94-7.15) and 104 (62.3%) had hepatitis B "e" antigen-positive serology. Median follow-up was sixty months (IQR = 36-93). In the 47 (28.1%) patients with F3-F4 baseline fibrosis, 7/47 (14.9%) regressed to F0-F1-F2 at last follow-up visit. Fibrosis regression was significantly associated with higher CD4+ cell counts (P= 0.009) and lower fasting triglyceride levels (P= 0.007) at TDF-initiation. In the 120 (71.9%) patients with F0-F1-F2-baseline fibrosis, 20/120 (16.7%) progressed to F3-F4 at last follow-up visit. Fibrosis progression was associated with male gender (P= 0.01), older age (P= 0.001), from low/moderate HBV-endemic country (P= 0.007), lower nadir CD4+ cell count (P= 0.03), higher fasting glycaemia (P= 0.03) and anaemia (P= 0.004) at TDF-initiation. Control of HBV replication at end of follow-up was extensive (88.1%), while no HBV-related factors emerged as predictors of progression/regression. Incidence of severe liver-related events was low (n= 4, rate = 0.5/100 person-years).
  
  
  
  Liver fibrosis levels are stable for most coinfected patients undergoing TDF, despite control of HBV replication. Nevertheless, a concerning amount of liver fibrosis progression did occur, which could be partly explained by metabolic abnormalities and past severe immunosuppression and requires further evaluation.
authors.affiliation: INSERM, UMR_S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: Anders
authors.initials: A
authors.lastname: Boyd
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, AP-HP, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bottero
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Miailhes
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lascoux-Combe
authors.affiliation: Institut de Médecine et d'Epidémiologie Appliquée, Paris, France.
authors.forename: Hayette
authors.initials: H
authors.lastname: Rougier
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, AP-HP, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.affiliation: Service Hépato-gastro-entérologie, Hôpital Saint-Antoine, Paris, France.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, AP-HP, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000821:virology; D018450:Disease Progression; D005260:Female; D005602:France; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy*; D006513:Hepatitis B e Antigens; D006515:Hepatitis B virus; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068698:Tenofovir / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D006513:Hepatitis B e Antigens; D000068698:Tenofovir
keywords: hepatocellular carcinoma; immunosuppression; liver cirrhosis; liver fibrosis; noninvasive markers