Liver disease is a major cause of morbidity among HIV-infected persons. There is limited information about the extent to which HIV disease severity influences liver disease progression, particularly early in the disease course when interventions may have the greatest impact.
We determined the incidence and predictors of advanced hepatic fibrosis measured by the FIB-4 index in a large and diverse population of HIV-infected patients without significant liver disease at baseline (FIB-4 <1.45). We used Cox proportional hazards analysis to examine factors associated with progression to FIB-4 ≥3.25, stratified by hepatitis C (HCV) status.
A total of 14,198 HIV-infected patients in care between January 2000 and March 2014 were included in the analysis, the majority of whom were male (82%) and had sex with men (58%) as a transmission risk factor. The prevalence of HCV coinfection was 15% and alcohol use disorder 9%. Progression to advanced fibrosis occurred in 1,386 patients (10%) in a median of 3 years during a total of 61,904 person-years of follow-up (PYFU) for an incidence of 2.2 per 100 PYFU overall and 4.7 per 100 PYFU among HIV-HCV coinfected patients. In multivariable analysis, HCV coinfection (adjusted hazard ratio [aHR] 1.85, 95% CI 1.63-2.11), HBV coinfection (aHR 1.45, 95% CI 1.17-1.81), alcohol use disorder (aHR 1.36, 95% CI 1.17-1.58) and diabetes (aHR 1.87, 95% CI 1.56-2.25) were associated with progression to advanced fibrosis. In addition, patients with lower time-varying CD4 count were more likely to progress, with the greatest risk in those with CD4 <100 cells/mm3 (aHR 6.93, 95% CI 5.80-8.27) compared with CD4 ≥500 cells/mm3. An increasing gradient of risk was also observed among patients with higher time-varying HIV viral load (VL), with the greatest risk in those with VL ≥100,000 copies/ml (aHR 2.60, 95% CI 2.19-3.08) compared with those who were suppressed. We observed similar findings for both HIV monoinfected and HIV-HCV coinfected patients in stratified analyses.
We found that both lower CD4 count and higher HIV VL were significantly associated with progression to advanced hepatic fibrosis, independent of the risk associated with traditional factors including HCV and HBV coinfection, alcohol, and diabetes. Our findings suggest that early treatment of HIV infection could mitigate liver disease.