BACKGROUND: We investigated changes in biomarkers of liver disease in HIV/HCV- coinfected individuals during successful combination antiretroviral therapy (cART) compared to changes in biomarker levels during untreated HIV-infection and to HIV-monoinfected individuals.
METHODS: Non-invasive biomarkers of liver disease [hyaluronic acid (HYA), APRI, FIB-4 and cytokeratin-18 (CK-18)] were correlated with liver histology in 49 HIV/HCV-coinfected patients. Changes in biomarkers over time were then assessed longitudinally in HIV/HCV-coinfected patients during successful cART (n=58), during untreated HIV-infection (n=59), and in HIV-monoinfected individuals (n=17). The median follow-up time was 3.4 years on-cART. All analyses were before starting HCV treatment.
RESULTS: Non-invasive biomarkers of liver disease correlated significantly with the histological METAVIR-stage (P<0.002 for all comparisons). The AUROC values for advanced fibrosis (≥F3-METAVIR) for HYA, APRI, FIB-4 and CK-18 were 0.86±0.05, 0.84±0.08, 0.80±0.09 and 0.81±0.07, respectively. HYA, APRI and CK-18 levels were higher in HIV/HCV-coinfected compared to HIV-monoinfected patients (P<0.01). In the first year on cART, APRI and FIB-4 scores decreased (-35% and -33%, P=0.1), mainly due to the reversion of HIV-induced thrombocytopenia, while HYA and CK-18 levels remained unchanged. During long-term cART, there were only small changes (<5%) in median biomarker levels. Median biomarker levels changed less than 3% during untreated HIV-infection. Three patients died from end-stage liver disease, and 10 from other causes.
CONCLUSIONS: Biomarkers of liver disease highly correlated with fibrosis in HIV/HCV-coinfected individuals and did not change significantly during successful cART. These findings suggest a slower than expected liver disease progression in many HIV/HCV-coinfected individuals, at least during successful cART.