title: Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus.
abstract: OBJECTIVE
  To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART).
  
  
  METHODS
  Retrospective analysis of a prospective cohort study.
  
  
  METHODS
  Italian HIV care centers participating to the ICONA Foundation cohort.
  
  
  METHODS
  Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up.
  
  
  METHODS
  Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD.
  
  
  RESULTS
  Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45-3.25 and 7.7% >3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4>3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB-4>3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART.
  
  
  CONCLUSIONS
  The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.
authors.affiliation: Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lorenzini
authors.affiliation: Clinic of Infectious Diseases, Maggiore Hospital, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.affiliation: Clinic of Infectious Diseases, La Sapienza University, Rome, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Lichtner
authors.affiliation: Department of Infectious Diseases, San Gerardo Hospital, Monza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lapadula
authors.affiliation: Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: Clinica delle Malattie Infettive, Università di Sassari, Sassari, Italy.
authors.forename: Giordano
authors.initials: G
authors.lastname: Madeddu
authors.affiliation: Department of Infection & Population Health Division of Population Health, Hampstead Campus, University College London, London, United Kingdom.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.affiliation: Clinic of Infectious Diseases, Department of Health Sciences, San Paolo Hospital, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.affiliation: Division of Infectious Diseases, Department of Medical Biotechnologies, University of Siena and Siena University Hospital, Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D016174:Hepacivirus / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000473:pathology* / Q000821:virology*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000473:pathology* / Q000821:virology*; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D019562:Viral Load / Q000379:methods
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral