Nonalcoholic fatty liver disease and hepatic fibrosis among perinatally HIV-monoinfected Asian adolescents receiving antiretroviral therapy

Abstract

To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10–25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA<400 copies/mL within the past 6 months), and had no history of chronic hepatitis B/C infection were enrolled. Participants were pre-classified into 2 subgroups (1:1 ratio) as participants with history of elevated versus normal aminotransferase enzymes. NAFLD was defined as hepatic steatosis (any severity) evaluated by liver ultrasonography. Significant hepatic fibrosis was defined as liver stiffness ≥7.4 kPa evaluated by transient elastography. Participants who met the criteria for protocol-defined NAFLD and/or hepatic fibrosis were re-assessed to evaluate disease progression (persistent versus transient hepatic abnormalities) at one year later. Of 120 participants, 62 (51.7%) were male, 7 (5.8%) had central obesity, and 19 (15.8%) had insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] >3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6–19.2) years and 10.5 (7.1–12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8–18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (≥2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7–511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1–289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance.

Prevalence and Risk Factors for Hepatic Steatosis in Children With Perinatal HIV on Early Antiretroviral Therapy Compared to HIV-Exposed Uninfected and HIV-Unexposed Children

“…In a study of Asian PHIV adolescents virologically suppressed on ART, the prevalence of hepatic steatosis using ultrasonography was 8% and hepatic fibrosis using TE was 9%, similar to the rates of hepatic steatosis and fibrosis using transient elastography with CAP in our study ( 35 ). In a French study from 2009, PHIV children had higher liver stiffness than HU controls with 17% having mild hepatic steatosis on ultrasound ( 36 ).…”

Prevalence of nonalcoholic fatty liver disease using noninvasive techniques among children, adolescents, and youths living with HIV

“…Prompt diagnosis and management may prevent disease progression, as the rate of success is higher when lifestyle changes are promoted early in life [59,60]. The hypothesis of a direct relationship between liver damage and HIV-infection plus ART treatment in this cohort is plausible and has been pointed out in previous studies [27,61]. However, the fact that apart from the CD4 + /CD8 + ratio, no HIV-related variables were independently associated with NAFLD, does not support the role of chronic inflammation or metabolic abnormalities secondary to ART as an underlying cause.…”

Gastrointestinal Diseases in Children Living with HIV

“…Liver injury may result from HIV infection itself but also from ART toxicity or comorbidities, including coinfection with hepatitis B and C viruses (HBV and HCV) and nonalcoholic fatty liver disease (NAFLD). Isolated hepatomegaly with normal or slightly raised transaminases (ALT less than three times the normal upper limit) is a relatively common finding in children living with HIV, which could be associated with nutritional deficiencies or NAFLD [ 85 ].…”