From the *Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda; †Westat, Rockville, MD; ‡Department of Infectious Diseases, Hospital Federal dos Servidores do Estado; §Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro; ¶Vertical Transmission Unit, Femina Hospital, Porto Alegre; ‖Department of Pediatrics, University of São Paulo Faculty of Medicine of Ribeirão Preto, Ribeirão Preto; and **Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Pediatr Infect Dis J. 2014 Feb;33(2):177-82. doi: 10.1097/INF.0b013e3182a01dfb.
Chronic liver disease has emerged as an important problem in adults with longstanding HIV infection, but data are lacking for children. We characterized elevated aspartate aminotransferase-to-platelet ratio index (APRI), a marker of possible liver fibrosis, in perinatally HIV-infected children.
The National Institute of Child Health and Human Development International Site Development Initiative enrolled HIV-infected children (ages 0.1-20.1 years) from 5 Latin American countries in an observational cohort from 2002 to 2009. Twice yearly visits included medical history, physical examination and laboratory evaluations. The prevalence (95% confidence interval) of APRI > 1.5 was calculated, and associations with demographic, HIV-related and liver-related variables were investigated in bivariate analyses.
APRI was available for 1012 of 1032 children. APRI was >1.5 in 32 (3.2%, 95% confidence interval: 2.2%-4.4%) including 2 of 4 participants with hepatitis B virus infection. Factors significantly associated with APRI > 1.5 (P < 0.01 compared with APRI ≤ 1.5) included country, younger age, past or current hepatitis B virus, higher alanine aminotransferase, lower total cholesterol, higher log10 current viral load, lower current CD4 count, lower nadir CD4 count, use of hepatotoxic nonantiretroviral (ARV) medications and no prior ARV use. Rates of APRI > 1.5 varied significantly by current ARV regimen (P = 0.0002), from 8.0% for no ARV to 3.2% for non-protease inhibitor regimens to 1.5% for protease inhibitor-based regimens.
Elevated APRI occurred in approximately 3% of perinatally HIV-infected children. Protease inhibitor-based ARVs appeared protective whereas inadequate HIV control appeared to increase risk of elevated APRI. Additional investigations are needed to better assess potential subclinical, chronic liver disease in HIV-infected children.
慢性肝病已成为长期感染 HIV 的成年人的一个重要问题，但儿童的数据却很缺乏。我们对经胎盘感染 HIV 的儿童的天门冬氨酸氨基转移酶/血小板比值指数（APRI）升高（一种可能的肝纤维化标志物）进行了特征描述。
美国国立儿童健康与人类发展研究所（NICHD）的国际现场发展倡议（IDI）于 2002 年至 2009 年在 5 个拉丁美洲国家招募了感染 HIV 的儿童（年龄 0.1-20.1 岁），并纳入一个观察队列。每两年进行一次就诊，包括病史、体检和实验室评估。计算了 APRI＞1.5 的患病率（95%置信区间），并在双变量分析中调查了 APRI 与人口统计学、HIV 相关和肝脏相关变量之间的关系。
1012 名儿童中有 1012 名提供了 APRI 数据。32 名（3.2%，95%置信区间：2.2%-4.4%）儿童的 APRI＞1.5，其中包括 4 名乙型肝炎病毒感染者中的 2 名。与 APRI≤1.5 相比，APRI＞1.5 显著相关的因素包括国家、年龄较小、过去或现在的乙型肝炎病毒感染、较高的丙氨酸氨基转移酶、较低的总胆固醇、较高的当前病毒载量对数 10、较低的当前 CD4 计数、较低的最低 CD4 计数、使用肝毒性非抗逆转录病毒（ARV）药物和无既往 ARV 治疗。目前 ARV 方案的 APRI＞1.5 发生率差异显著（P=0.0002），无 ARV 治疗的发生率为 8.0%，非蛋白酶抑制剂方案的发生率为 3.2%，基于蛋白酶抑制剂的方案的发生率为 1.5%。
约 3%的经胎盘感染 HIV 的儿童出现 APRI 升高。基于蛋白酶抑制剂的 ARV 似乎具有保护作用，而 HIV 控制不足似乎会增加 APRI 升高的风险。需要进一步研究以更好地评估 HIV 感染儿童潜在的亚临床慢性肝病。
