To the Editor: Rubio et al (1) studied 26 HIV-infected children in respect to liver injury because they are exposed to long-term antiretroviral drug and cytopathic effect of HIV. The authors evaluated the performance of noninvasive tests in detecting liver injury and decided that evaluation of hepatic disease with noninvasive procedures is feasible in HIV-1 chronically infected children. However, we should discuss some important points regarding some of the noninvasive tests, namely FibroTest (FT) and ActiTest (AT).
Several studies have demonstrated the predictive value of FT-AT in patients infected with hepatitis C and B viruses for the assessment of fibrosis and of necroinflammatory activity (2–4). FT was found to be an effective alternative to liver biopsy in patients with both chronic hepatitis B and C (5). In some other studies, however, FT was not found to be as accurate as described in the early studies (6). Rossi et al (6) found that 21% of the patients who were predicted to have significant fibrosis by FT scores had only minimal fibrosis by histology and, conversely, 18% of the patients who were not supposed to have fibrosis according to the FT score had significant histological fibrosis. In a review comparing the biochemical markers with liver biopsy, it was stated that neither clinical nor laboratory markers, individually or in combination, predict accurately the degree of necroinflammatory activity or the level of fibrosis in the liver (7). In a recent study (8) of children with chronic hepatitis C, the authors determined discordance between FT-AT and histological data (METAVIR) in more than half of the patients. Recently, we investigated whether the noninvasive serum markers FT-AT reliably predicted the histological stage of fibrosis and/or activity and decreased the need for liver biopsy in 25 children (median age 9 years [3–18]) with naïve chronic HBV infection (9). FT-AT was assessed at the time of liver biopsy. Test scores were computed on the BioPredictive Web site (10). Appropriate cutoff values were previously described by Poynard et al (2). Values <0.31 in FT correspond to insignificant fibrosis and those <0.37 in AT indicate insignificant activity. Test results were compared with histological data determined according to Ishak classification (Tables 1 and 2). FT predicted insignificant fibrosis in 14 of 23 patients (61%). On the contrary, none of the 9 patients with significant fibrosis and neither of the 2 patients with insignificant fibrosis in histology had corresponding fibrosis stage indicated by FT scores. The prevalence of significant fibrosis in histology was 0.36 and the negative predictive value for excluding significant fibrosis at appropriate cutoff level was 61% (14/23). AT negative predictive value for excluding significant activity (prevalence 0.16) was 100%. Moreover, AT accurately predicted the stage of activity in only 10 patients (40%), whereas it overestimated the stage of activity in 15 patients (60%). Most of the reports in adults have not shown such poor performance. The reason for the poor performance of FT-AT in children is obscure. Conversely, transient elastography (FibroScan, EchoSens, Paris, France), which is a novel, rapid bedside method, displays good correlation with histology (11) and can serve as a useful screening tool to assess liver fibrosis (12,13).
Second, the authors did not perform liver biopsy to evaluate fibrosis and necroinflammation. Indeed, liver biopsy is not free of complications. Pain is reported in one-third of the patients. Life-threatening complications may occur in 3 of 1000 cases and prolong hospitalization. Death is reported in 3 of 10,000 cases (14–16). The diagnostic value of liver biopsy is limited by the sampling variability: the smaller the biopsy is, the larger the discordance for stage of the fibrosis and necroinflammatory activity scores (17–19). On the contrary, liver biopsy is the current criterion standard to investigate fibrosis and activity. Therefore, FT-AT should be compared with liver biopsy to validate it in deciding degree of liver injury.
In conclusion, FT-AT does not seem suitable and “ready for prime time” to use in deciding the degree of liver injury in children. We need additional work including validation studies as well.
1. Rubio A, Monpoux F, Huguon E, et al
. Noninvasive procedures to evaluate liver involvement in HIV-1 vertically infected children. J Pediatr Gastroenterol Nutr 2009; 49:599–606.
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. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C. Comp Hepatol 2004; 3:8–19.
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. Biomarkers of liver fibrosis. Adv Clin Chem 2008; 46:131–160.
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. Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B 25. J Hepatol 2003; 39:222–230.
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9. Sökücü S, Gökçe S, Güllüoğlu M, et al. The role of the non-invasive serum marker FibroTest-ActiTest in the prediction of histological stage of fibrosis and activity in children with naïve chronic hepatitis B infection. Scand J Infect Dis
2010; Apr 29. [Epub ahead of print]
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. Accessed September 8, 2010.
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