Page 222 - SAHCS HIVMed Journal Vol 20 No 1 2019
P. 222

Page 3 of 6  Original Research


              These values have been reported to be predictive of significant   participants receiving nevirapine-containing ART regimens
              hepatic fibrosis and were adopted for this study. 10,23,24,25      had significant fibrosis based on the FibroTest, which has
              All statistical analyses were performed using Stata 13.0 (Stata   been validated in other settings. 19,20  One of the three
              Corp., College Station, Texas, USA) software package and a   participants co-infected with HBV had significant fibrosis as
              p-value of < 0.05 was considered statistically significant.  determined by the FibroTest. When we performed the test for
                                                                    agreement among the non-invasive algorithms, there was a
              Ethical consideration                                 moderate agreement between FIB-4 index and  APRI test
                                                                    (k  =  0.46),  fair  agreement  between  (1)  FibroTest  and  FIB-4
              The study protocol was approved by the Joint Parirenyatwa
              Hospital and College of Health Sciences Research Ethics   index  (k  =  0.40)  and  (2)  between  FibroTest  and  APRI  test
              Committee (JREC Ref: 45/14). All participants gave written   (k = 0.25). The AST:ALT ratio was in poor agreement with all
              informed patient consent or assent. Consent was granted by   three other algorithms: FibroTest (k = 0.08), FIB-4 index
              parents or guardians in the case of minors.           (k = 0.10) and APRI test (k = 0.08).
              Results                                               Individual biomarkers in fibrosis and non-

              Characteristics of the study population               fibrosis as defined by FibroTest
                                                                    We  compared  individual  serum  biomarkers  between
              We enrolled 79 HIV-infected individuals with mean age and   participants  with  significant  fibrosis  and  those  without
              standard deviation (s.d.) of 41 and 11 years, respectively. The   as  defined  by  FibroTest. Total  bilirubin and  A-2M
              majority of participants (65.8%; n = 55) were female and the
              average body mass index (BMI) was 23 kg/m , with 14.7%   concentrations were significantly elevated in participants
                                                    2
              being underweight, 61.8% being normal weight, 14.7% being   with fibrosis, median (IQR) 7  μmol/L (5–46) versus 5
              overweight and 8.8% being obese. Seventy-six per cent of the   μmol/L (4–7) ( p = 0.029) and 1.5 g/L (1.1–2.9) versus 0.2 g/L
              participants were on nucleoside reverse transcriptase   (0.1–0.8) ( p < 0.001), respectively, when compared to those
              inhibitor (NRTI) plus non-nucleoside reverse transcriptase   without  fibrosis.  However,  after  adjusting  for  multiple
              inhibitors (NNRTI), 17.7% were taking NRTIs plus protease   comparisons with the Bonferroni adjustment, only  A-2M
              inhibitor (PI) whilst 6.3% were taking NRTIs only. The   ( p  < 0.001) remained significant. The findings are
              duration on ART ranged from 1 to 13 years with a median of   summarised in Table 3.
              four years and six months and interquartile range (IQR) of
              2–7 years. Based on serological tests, 3.8% (n = 3) of study   Individual biomarkers in fibrosis and non-
              participants had HIV/HBV co-infection. The demographic   fibrosis defined by aspartate aminotransferase
              characteristics of the study participants are shown in Table 2.  to platelet ratio index test

              Utility of algorithms for the prediction of           We further compared individual serum biomarkers based on
              hepatic fibrosis                                      APRI test strata. Aspartate aminotransferase and Apo A-1
                                                                    were significantly  elevated  in participants with  fibrosis
              We first determined the prevalence of fibrosis in our study   median  (IQR) 50  (32–77) IU/L versus  28 (23–36)  IU/L
              participants using each of the four algorithms (FibroTest,   ( p  =  0.005) and 1.6 (1.2–1.8) g/L versus 0.9 (0.5–1.5) g/L
              FIB-4 index, APRI test and AST:ALT ratio). The prevalence of   ( p  =  0.027),  respectively, when  compared  to those  without
              fibrosis according to each algorithm were: FibroTest (19%),
              FIB-4 index (21.5%),  APRI test (12.7%) and  AST:ALT ratio
              (79.7%), as shown in Figure 1.                           90
                                                                                                            79.70
                                                                       80
              The average prevalence of fibrosis was 17.7% using the three   70
              comparable algorithms (FibroTest, FIB-4 index and  APRI
              test) but increased to 33.2% when  AST:ALT ratio was     60
              included. Notably, 19.4% (n = 7) of the 36/79 (45.6%)   Percentage  50

              TABLE 2: Demographic characteristics of study participants.  40
                                                                       30
              Parameter                     Participants (n = 79)             19        21.50
              Gender: Females n (%)            52 (65.8)               20                         12.70
              Age (years) mean ± s.d.           41 ± 11                10
              Height (metres) median (IQR)   1.70 (1.60–1.70)           0
              Weight (kg) median (IQR)         66 (56–75)                   Fibro test  FIB-4 index  APRI test  AST/ALT rao
              BMI (kg/m ) mean ± s.d.           23 ± 4.4                                   Biomarkers
                    2
              CD4+ count (cells/uL) median (IQR)  416 (254–624)
              HIV/HBV co-infection, n (%)       3 (3.8)             FIGURE  1:  Prevalence  of  hepatic  fibrosis  as  determined  by  non-invasive
              Period on ART (years) median (IQR)  4.5 (2–7)         biomarkers. The figure shows the prevalence (%) of significant liver fibrosis in
                                                                    antiretroviral  therapy-experienced  participants  as  determined  by  the  non-
              Patients taking alcohol, n (%)   11 (13.9)            invasive  algorithms  (FibroTest  19%,  Fibrosis-4  [FIB-4]  index  21.5%,  aspartate
              s.d., standard deviation; IQR, interquartile range; BMI, body mass index; HIV/HBV, human   aminotransferase  to  platelet  ratio  index  [APRI]  test  12.7%  and  aspartate
              immunodeficiency virus/hepatitis B virus; ART, antiretroviral therapy.  aminotransferase to alanine aminotransferase [AST:ALT] ratio 79.7%).

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