title: Prevalence and incidence of liver dysfunction and assessment of biomarkers of liver disease in HIV-infected Asian children.
abstract: BACKGROUND
  We determined the prevalence and incidence of liver dysfunction before and after initiation of combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database.
  
  
  METHODS
  Data from children initiated on cART between 2 and 18 years of age with baseline alanine aminotransferase (ALT) available before and at least once after cART initiation in TREAT Asia Pediatric HIV Observational Database between 2008 and 2012 were analyzed. Prevalence and incidence of liver dysfunction and biomarkers including the aspartate aminotransferase to platelet ratio index and FIB4 index (a noninvasive panel to stage liver disease) were assessed.
  
  
  RESULTS
  Data from 1930 children were included. Their median age was 6.9 years; 49% were male; 98% were perinatally infected and 94% were initiated on non-nucleoside reverse transcriptase-based cART regimens. Before cART, the prevalence of ALT ≥3 times the upper limit of normal (×ULN) was 5.8%. There were 8.5% of children with aspartate aminotransferase to platelet ratio index >1.5 (suggestive of liver fibrosis) and 2.7% with FIB4 index >1.3 (predictive of possible cirrhosis). Among the 1143 cases with normal baseline ALT (≤1×ULN), the incidence of ALT 3×ULN after cART was 1.19 of 1000 person-months (95% confidence interval: 0.93-1.51). Two of 350 with available tests (0.6%) met Hy's law (ALT >3×ULN and total bilirubin >2×ULN). By multivariate analysis, baseline hemoglobin <7.5 g/dL was a predictor of ALT >3×ULN, whereas age 5-9 years at cART initiation was protective for liver dysfunction.
  
  
  CONCLUSIONS
  We demonstrated a low prevalence and incidence of liver dysfunction before and after cART initiation in children with normal baseline chemistries. In this population facing life-long cART, prospective surveillance for emergence of liver disease is warranted.
authors.affiliation: *Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; †HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‡TB/HIV Department, National Pediatric Hospital, Phnom Penh, Cambodia; §The Kirby Institute, University of New South Wales, Sydney, Australia; ¶Department of Child Health, Sanglah Hospital, Udayana University, Bali, Indonesia; ‖Infectious Disease Department, National Hospital of Pediatrics, Hanoi, Vietnam; **Research Unit, National Center for HIV/AIDS, Dermatology and STDs, Social Health Clinic, Phnom Penh, Cambodia; ††Faculty of Medicine, University of Health Sciences, Phnom Penh, Cambodia; ‡‡Department of Pediatrics, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; §§Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; ¶¶Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; ‖‖Infectious Disease Department, Children's Hospital 1, Ho Chi Minh City, Vietnam; ***Infectious Disease Department, Children's Hospital 2, Ho Chi Minh City, Vietnam; †††Y.R. Gaitonde Centre for AIDS Research and Education (YRG CARE), Chennai, India; ‡‡‡Department of Pediatrics, Hospital Raja Perempuan Zainab II, Kelantan, Malaysia; §§§Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; ¶¶¶Pediatric Allergy-Immunology Division, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; ‖‖‖Department of Pediatrics, Hospital Likas, Kota Kinabalu, Malaysia; ****Department of Pediatrics, Penang Hospital, Penang, Malaysia; and ††††TREAT Asia/amfAR-The Foundation for AIDS Research, Bangkok, Thailand.
authors.forename: Linda
authors.initials: L
authors.lastname: Aurpibul
authors.forename: Torsak
authors.initials: T
authors.lastname: Bunupuradah
authors.forename: Sam
authors.initials: S
authors.lastname: Sophan
authors.forename: David
authors.initials: D
authors.lastname: Boettiger
authors.forename: Dewi K
authors.initials: DK
authors.lastname: Wati
authors.forename: Lam V
authors.initials: LV
authors.lastname: Nguyen
authors.forename: Vonthanak
authors.initials: V
authors.lastname: Saphonn
authors.forename: Rawiwan
authors.initials: R
authors.lastname: Hansudewechakul
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.forename: Pagakrong
authors.initials: P
authors.lastname: Lumbiganon
authors.forename: Khanh H
authors.initials: KH
authors.lastname: Truong
authors.forename: Viet C
authors.initials: VC
authors.lastname: Do
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.forename: Nik K N
authors.initials: NK
authors.lastname: Yusoff
authors.forename: Kamarul
authors.initials: K
authors.lastname: Razali
authors.forename: Nia
authors.initials: N
authors.lastname: Kurniati
authors.forename: Siew M
authors.initials: SM
authors.lastname: Fong
authors.forename: Revathy
authors.initials: R
authors.lastname: Nallusamy
authors.forename: Annette H
authors.initials: AH
authors.lastname: Sohn
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001208:Asia; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008107:Liver Diseases / Q000453:epidemiology*; D008297:Male; D010976:Platelet Count; D015995:Prevalence; D012189:Retrospective Studies
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase