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Liver Markers Worse in Youth With Than Without HIV and Climb Over Time
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20th International AIDS Conference, July 20-25, 2014, Melbourne
Mark Mascolini
FIB-4 and APRI, two noninvasive markers of liver disease, proved higher (worse) in HIV-positive teens than in HIV-negative youth 15 to 20 years old, according to results of a 1785-person analysis of two US cohorts [1]. Among youngsters who had two or more study visits, both FIB-4 and APRI rose over time.
National Institutes of Health (NIH) researchers and collaborators noted that HIV infection and antiretroviral therapy may contribute to liver problems, even in people without hepatitis B or C infection. FIB-4 (a noninvasive fibrosis marker) and APRI (aspartate aminotransferase-to-platelet ratio index) have been validated in adults with HIV/HCV coinfection, the researchers observed, but their meaning in HIV-positive youth is not well understood.
To address these issues, the NIH team analyzed prevalence, progression, and predictors of FIB-4 and APRI in two prospective US cohorts, REACH and PACTG 219/219c. Study participants were 15 to 20 years old and had either HIV (without HCV or HBV) or no infection. FIB-4 above 1.5 or APRI above 0.5 indicates mild/moderate fibrosis, while FIB-4 above 3.25 or APRI above 1.5 indicates advanced fibrosis.
All 1785 cohort members had at least one study visit, and about 70% had measures from two or more visits through a median follow-up of 2 years. While 1042 cohort members were perinatally infected with HIV, 570 were behaviorally infected, and 173 were HIV-negative. Median age at liver function testing stood at 15.6 years. Most cohort members, 59%, were young women, 57% were non-Hispanic black, 27% Hispanic, and 13% non-Hispanic white. One quarter of youngsters with HIV were not taking antiretrovirals. Overall median CD4 count in HIV-positive youth measured 505 and median viral load 2033 copies.
A higher proportion of youth with than without HIV had an APRI above 0.5, suggesting at least mild-to-moderate fibrosis (12% versus 3%, P = 0.002). Prevalence of an APRI above 1.5, suggesting significant fibrosis, was also higher in youth with than without HIV (2% versus 1%). Proportions of study participants with FIB-4 above 1.5 were 3% with HIV and 1% without HIV.
Among all study participants, a model adjusted for HIV status, gender, body mass index (BMI) z score, viral load, and antiretroviral use determined that having HIV infection, being male, and having a low BMI z score independently predicted an APRI above 0.5 (all P < 0.02). Among HIV-positive study participants, male gender, a CD4 count below 350, and a viral load above 400 copies independently predicted an APRI above 0.5 (all P < 0.02).
In HIV-positive youth, incidence of progression to APRI above 0.5 measured 7.5 per 100 person-years while incidence to progression above 1.5 measured 1.4 per 100 person-years. (Incidence of 7.5 per 100 person-years means 7 or 8 of every 100 youngsters had APRI-measured progression every year.) Rates of progression to FIB-4 above 1.5, above 2.5, and above 3.25 were 1.6, 0.6, and 0.3 per 100 person-years.
After statistical adjustment for age, gender, and race or ethnicity, average APRI was 38% higher in the HIV group than in the uninfected group (P < 0.001) and average FIB-4 was 15% higher (P < 0.001). Average APRI was 34% higher and FIB-4 20% higher in males than females (P < 0.001 for both differences). Average APRI and FIB-4 did not differ between HIV-positive youth infected behaviorally and those infected perinatally.
HIV-positive youth with a baseline CD4 count below 350 had more than a doubled risk of progression to APRI above 0.5 (incidence rate ratio [IRR] 2.14, 95% confidence interval [CI] 1.58 to 2.90, P < 0.001) and more than a tripled risk of progression to APRI above 1.5 (IRR 3.62, 95% CI 1.91 to 6.85, P < 0.001). A baseline CD4 count below 350 conferred even higher risks of progression to FIB-4 above 1.5 (IRR 3.87, 95% CI 2.14 to 7.00, P < 0.001), above 2.5 (IRR 8.64, 95% CI 2.84 to 26.24, P < 0.001), and above 3.25 (IRR 7.35, 95% CI 1.48 to 36.42, P = 0.014).
In models adjusted for HIV exposure category (perinatal or behavioral), gender, and BMI z score, FIB-4 scores rose significantly in all HIV-positive youth at a rate of 6% per year of age (P < 0.001). APRI rose significantly by 2% per year of age in perinatally infected youngsters (P = 0.007) but not in behaviorally infected youth. Males, youngsters with a CD4 count below 350 or a viral load above 400 copies, and those not taking antiretrovirals had consistently higher FIB-4 scores over time (P < 0.001). The same four variables predicted significantly higher APRI scores over time (P < 0.001).
The investigators concluded that average APRI and FIB-4 scores were higher in HIV-positive youth than in HIV-negative youngsters and remained so after adjustment for relevant variables. "Among HIV-infected youth," they noted, "progression to values suggesting subclinical fibrosis or worse was common." The investigators noted that incidence rates for APRI-measured progression are comparable to those recorded in studies of children with HIV. The researchers are now validating these findings in analyses using clinical disease staging in this HIV age group.
Reference
1. Kapogiannis B, Leister E, Siberry G, et al. prevalence of and progression to abnormal non-invasive markers of liver disease (APRI and FIB-4) among US HIV-infected youth. AIDS 2014. 20th International AIDS Conference. July 20-25, 2014. Melbourne. Abstract MOAB0102.
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