Use of Simple Noninvasive Biomarkers to Predict Liver Fibrosis in HIV/HCV Coinfection in Routine Clinical Practice

J Macías; J González; E Ortega; C Tural; E Cabrero; A Burgos; JA Pineda; on behalf of the GRAFIHCO Study Team


HIV Medicine. 2010;11(7):439-447. 

In This Article

Abstract and Introduction


Background Simple noninvasive tests to predict fibrosis, as an alternative to liver biopsy (LB), are needed. Of these, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the Forns index (FI) have been validated in HIV/hepatitis C virus (HCV) coinfection. However, these indexes may have lower diagnostic value in situations other than the circumscribed conditions of validation studies. We therefore examined the value of the APRI and FI in HIV/HCV-coinfected patients for the detection of significant fibrosis in real-life conditions.
Patients and methods HIV/HCV-coinfected patients who had participated in a multicentre cross-sectional retrospective study were selected if they had undergone an LB within 24 months before the last visit. The predictive accuracy of the APRI and FI was measured using the areas under receiver-operating-characteristic curves (AUROCs). Diagnostic accuracy was determined using the positive (PPV) and negative (NPV) predictive values.
Results A total of 519 coinfected individuals were included in the study. The AUROC [95% confidence interval (95% CI)] of the APRI was 0.67 (0.66–0.71) and that of the FI was 0.67 (0.62–0.71). The PPV of the APRI was 79% and its NPV was 66%. The PPV of the FI was 74% and its NPV was 64%. LB length was available and was ≥15 mm in 120 individuals. In this group, the PPV of the APRI was 85%, and that of the FI was 81%. Using these indexes, 22% of patients could be spared LB. Applying both models sequentially, 30% of patients could be spared LB.
Conclusions In HIV/HCV-coinfected patients, the diagnostic accuracy of the APRI in real-life conditions was similar to that in the validation studies. The FI performed less well. However, combining the two indexes to make decisions on anti-HCV therapy may prevent a significant proportion of patients from having to undergo LB.


The evaluation and quantification of liver fibrosis in patients with HIV and hepatitis C virus (HCV) infection has multiple implications. For example, the prognosis of HCV infection is estimated from the stage of fibrosis. Given that liver disease is a leading cause of death in HIV/HCV-coinfected patients on highly active antiretroviral therapy (HAART),[1] the importance of fibrosis diagnosis cannot be understated. In addition, therapeutic decisions regarding anti-HCV treatment are usually guided by fibrosis stage. The limited efficacy of the pegylated interferon plus ribavirin combination in HIV/HCV coinfection, and its manifold adverse effects, has led to the practice of restricting this therapy to patients with higher risk of progressive liver disease. Thus, according to the recommendations of international guidelines and panels of experts, patients with fibrosis extending beyond the portal tracts would be candidates to receive therapy.[2,3] Finally, severe liver enzyme elevations during antiretroviral therapy are more frequent in patients with more advanced fibrosis, particularly among coinfected patients on nonnucleoside reverse transcriptase inhibitors.[4–6] Consequently, the determination of the liver fibrosis may lead us to select a safer HAART regimen for HIV/HCV-coinfected patients with advanced disease.

Liver biopsy (LB) has been the gold standard method for the diagnosis of fibrosis. However, it is invasive and limited because of variability issues.[7,8] In addition, it is costly and not easily accessible in many health care settings. Finally, expert pathologists in liver diseases are not widely available. Thus, reliable and financially viable noninvasive tests to diagnose fibrosis are needed, particularly in low-resource settings.

A high proportion of HIV/HCV-coinfected patients can be classified for fibrosis using simple blood indexes.[9–17] These tests are economical to use. However, the diagnostic value of these indexes in HIV/HCV-coinfected patients has been evaluated in specific validation studies usually carried out in tertiary care centres. It is not known whether the results obtained in the circumscribed conditions of validation studies are applicable to real-life practice. Diagnostic tests can perform less well in real-life practice, mainly because of higher variability. In a clinical setting, outside a controlled study, there are a number of sources of variability. The diagnosis of fibrosis is particularly prone to variability among observers.[7] Moreover, blood tests may also show variability among different laboratories.[18] Finally, the overall performance of tests depends on the prevalence of the diagnostic target, and thus may not be reproducible in different epidemiological settings.[19] In the light of these issues, we examined the value of the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the Forns index (FI) in HIV/HCV-coinfected patients for the detection of significant fibrosis in real-life conditions.


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