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.
Highlights
In the combination of antiretroviral therapy era, mortality associated with human immunodeficiency virus (HIV) and opportunistic infections have dramatically declined, leading to the significantly improved survival for HIV-infected children and adults [1,2]
Baseline alanine aminotransferase (ALT) >30 U/L, and homeostasis model assessment of insulin resistance (HOMA-IR) >3.16 were independently associated with persistent hepatic abnormalities
nonalcoholic fatty liver disease (NAFLD) has been identified in 31–65% of HIV-monoinfected adults, and was independently associated with male sex, obesity, dyslipidemia, insulin resistance, and elevated serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio [6,7,8,9]
Summary
In the combination of antiretroviral therapy (cART) era, mortality associated with HIV and opportunistic infections have dramatically declined, leading to the significantly improved survival for HIV-infected children and adults [1,2]. The increased burden of liver-related mortality, in both adults and children living with HIV, has drawn a great deal of clinical attention. Nonalcoholic fatty liver disease (NAFLD), an important complication of obesity, has been increasingly recognized in this population with a prevalence of 11–17% [4]. Hepatic fibrosis is a consequence of NAFLD which may progress to cirrhosis and eventually hepatocellular carcinoma (HCC) [10]. This condition has been found in 15–42% of HIV-monoinfected individuals, and was linked to diabetes, and increased ALT and gamma-glutamyl transferase (GGT) [8,11]. The impact of antiretroviral agents, nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) on NAFLD [6,7,8] and hepatic fibrosis [8,11] among HIV-monoinfected adults are still controversial
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