Prevalence and Predictors of Elevated Aspartate Aminotransferase-to-Platelet Ratio Index in Latin American Perinatally HIV-infected Children

Abstract

Background 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 (AST)-to-platelet ratio index (APRI ), a marker of possible liver fibrosis, in perinatally HIV-infected children. Methods NISDI [NICHD (National Institute of Child Health and Human Development) International Site Development Initiative] enrolled HIV-infected children (ages 0.1-20.1 years) from five Latin American countries in an observational cohort from 2002–2009. Twice yearly visits included medical history, physical examination and laboratory evaluations. The prevalence (95% confidence interval [CI]) of APRI>1.5 was calculated and associations with demographic, HIV-related and liver-related variables were investigated in bivariate analyses. Results APRI was available for 1012 of 1032 children. APRI was >1.5 in 32 (3.2%, 95% CI: 2.2%-4.4%) including 2 of 4 participants with hepatitis B (HBV) infection. Factors significantly associated with APRI>1.5 (p<0.01 compared to APRI≤1.5) included country, younger age, past or current HBV, higher alanine aminotransferase, lower total cholesterol, higher log10 current viral load, lower current CD4 count, lower nadir CD4 count, use of hepatotoxic non-antiretroviral (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 (PI) regimens to 1.5% for PI-based regimens. Conclusions Elevated APRI occurred in approximately 3% of perinatally HIV-infected children. PI-based ARVs appeared protective while 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.

Prevalence of and progression to abnormal noninvasive markers of liver disease (aspartate aminotransferase-to-platelet ratio index and Fibrosis-4) among US HIV-infected youth

“…Congruent with our above findings, the prevalence of evidence of at least mild to moderate fibrosis or worse (APRI > 0.5 or FIB-4 >1.45) was also consistently higher among HIV infected participants compared to their uninfected counterparts, though only statistically significant for APRI. Our prevalence rate of APRI >0.5 and >1.5 was 10% and 2%, respectively which was comparable to another domestic study of HIV-infected children whose rates were 6.5% and 0.8%[33], respectively and slightly lower compared to a Latin American study of HIV-infected children whose rate of APRI > 1.5 was 3.2%[32]. The smaller evaluable sample for FIB-4 showed a similar trend that did not achieve statistical significance.…”

“…Non-invasive markers of liver disease such as the Fibrosis-4 (FIB-4) score [based on the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), the platelet count and patient age] and the AST-to-platelet ratio index (APRI), have both been validated for identifying liver fibrosis and cirrhosis in adults with viral hepatitis[23–31]. While experience with these makers is extensive in adults, only a single study has compared APRI and liver biopsy in children[28] and there is little experience with these markers in children with HIV infection[32, 33]. …”

Elevated Aspartate Aminotransferase-to-Platelet Ratio Index in Perinatally HIV-Infected Children in the United States

“…This lower prevalence among HIV-infected children is likely attributable to lower rates in HIV-infected children compared to HIV-infected adults of other factors that contribute to liver problems, such as viral hepatitis and alcohol use (only 36% of perinatal HIV AMP participants reported alcohol use [11]). The prevalence of APRI > 1.5 in this US pediatric cohort is also substantially lower than the 3.2% prevalence reported in a large group of children in Latin America [12]. In addition to possible differences in host genetic factors and environmental exposures, children in the US PHACS cohort were older than children in the Latin American study and had received ART for a longer time.…”

Implementation of Occult Hepatitis Screening in the Spanish Cohort of HIV-infected Pediatric Patients

“…Recently published studies have shown that the sensitivity of the APRI index depends on the etiology of the chronic liver disease: its accuracy is acceptable for assessing liver fibrosis in patients with cHCV and NAFLD, but not for cHBV (129,131,169,170). Interestingly protease inhibitor-based cART was protective (111,116 (116).…”

“…None of the existing NITs have had their performance in HIV-positive pediatric patients evaluated so far, except for a few recent papers, the first to try to tackle this issue among perinatally HIV-infected children. Accordingly, more studies are needed to set pediatric cut-off serum biomarker values and standardized measurements for TLE in HIV-infected children (23,(116)(117)(118). It is known that vaccination against HBV is highly protective despite the loss of detectable anti-HBs in the healthy population, and postvaccinal response assessment is not routinely required except in children at higher risk of HBV infection (from 9 months of life for babies born of HBV infected mothers, hemodialysis, household contacts, celiac disease, HIV infection, any condition requiring immunosuppression), in whom it is advisable to 61 determine the anti-HBs levels in order to assess the minimum protective level of 10mIU/mL.…”