Linda Aurpibul1, Torsak Bunupuradah, Sam Sophan, David Boettiger, Dewi K Wati, Lam V Nguyen, Vonthanak Saphonn, Rawiwan Hansudewechakul, Kulkanya Chokephaibulkit, Pagakrong Lumbiganon, Khanh H Truong, Viet C Do, Nagalingeswaran Kumarasamy, Nik K N Yusoff, Kamarul Razali, Nia Kurniati, Siew M Fong, Revathy Nallusamy, Annette H Sohn. 1. *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.
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.
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.
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