Assessing mortality in women with hepatitis C virus and HIV using indirect markers of fibrosis

Abstract

Objective: Co-infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in HIV-infected individuals. However, predictors of mortality are poorly defined and most studies have focused predominantly on co-infection in men. We evaluated whether two indirect markers of hepatic fibrosis, aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 scores, were predictive of mortality in a well defined longitudinal cohort of HCV/HIV-co-infected women on HAART.

Methods: HCV/HIV-co-infected women on antiretroviral therapy enrolled in Women's Interagency HIV Study (WIHS), a National Institutes of Health-funded prospective, multicenter, cohort study of women with and at risk for HIV infection were included. Using Cox regression analysis, associations between APRI and FIB-4 with all-cause mortality were assessed.

Results: Four hundred and fifty HCV/HIV-co-infected women, of whom 191 women died, had a median follow-up of 6.6 years and 5739 WIHS visits. Compared with women with low APRI or FIB-4 levels, severe fibrosis was significantly associated with an increased risk of all-cause mortality {APRI: hazard ratio 2.78 [95% confidence interval (CI) 1.87, 4.12]; FIB-4: hazard ratio 2.58 (95% CI 1.68, 3.95)}. Crude death rates per 1000 patient-years increased with increasing liver fibrosis: 34.8 for mild, 51.3 for moderate and 167.9 for severe fibrosis as measured by FIB-4. Importantly, both APRI and FIB-4 increased during the 5 years prior to death for all women: the slope of increase was greater for women dying a liver-related death compared with nonliver-related death.

Conclusion: Both APRI and FIB-4 are independently associated with all-cause mortality in HCV/HIV-co-infected women and may have clinical prognostic utility among women with HIV and HCV.

Fig. 1. Aspartate aminotransferase-to-platelet ratio index data for 153 hepatitis C virus/HIV-co-infected women on HAART who died and had at least two fibrosis marker assessments (aspartate aminotransferase-to-platelet ratio index or FIB-4) available within 5 years of their death

The figure depicts aspartate aminotransferase-to-platelet ratio index (APRI) data from the last available fibrosis marker assessment up to 5 years before death for 133 nonliver-related (a: upper panel) and for 20 liver-related (b: lower panel) deaths. The solid, black curve is the regression line. APRI is depicted on a log-scale with cut-off lines for low (<0.5) and high (>1.5) values.

Fig. 2. FIB-4 data for 153 hepatitis C virus/HIV-co-infected women on HAART who died and had at least two fibrosis marker assessments (aspartate aminotransferase-to-platelet ratio index or FIB-4) available within 5 years of their death

The figure depicts FIB-4 data from the last available fibrosis marker assessment up to 5 years before death for 133 nonliver-related (a: upper panel) and for 20 liver-related (b: lower panel) deaths. The solid, black curve is the regression line. FIB-4 is depicted on a log-scale with cut-off lines for low (<1.5) and high (>3.25) values.