The Natural History of FIB-4 Score Progression among HIV/HCV co-infected Adults in an Outpatient Clinic

Background: Studies have documented more rapid progression of HCV-associated liver fibrosis in patients co-infected with HIV. However, the natural history of HCV infection in both mono-infected and co-infected patients remains highly variable. The patterns and predictors of fibrosis progression in the HIV/HCV co-infected population are not fully characterized. Given the invasiveness of serial liver biopsies, Fibrosis-4 score (FIB-4), a composite of non-invasive biomarkers that correlate with fibrosis stage, is increasingly used. We used FIB-4 to study the natural history of liver disease progression in a cohort of co-infected patients and evaluated predictors of progression to cirrhosis over 5 years prior to treatment with direct acting agents (DAAs).

Methods: All HIV/HCV co-infected patients receiving care at Yale-New Haven Hospital from February 2014 through April 2016 with a minimum of 3 annual FIB-4 scores were included in the study. Annual FIB-4 scores dating back 5 years were calculated from the most recent FIB-4 score or the last FIB-4 prior to DAA treatment initiation. FIB-4<1.45 indicated absence of cirrhosis and FIB-4>3.25 indicated cirrhosis. Baseline demographics and clinical characteristics such as HCV genotype, HIV viral load and CD4 counts were collected. Patients were further categorized based on FIB-4 progression over the course of 5 years.

Results: The sample of 83 men and 43 women had a mean age of 56.9 years; 31.7% were white, 54.0% were black. Injection drug use (IDU) was the major risk factor for HCV acquisition (77.0%) and the most common genotype was genotype 1 (83.8%). 71 patients (60.2%) had CD4 count >500 cells/mm3, and the majority (90.0%) had HIV viral loads 3.25, 67 (53.2%) had FIB-4 remain <3.25, and 29 (23.0%) had FIB-4 remain >3.25. For patients who progressed to >3.25, median FIB-4 progressed from 2.59 to 4.13, while for patients who remained <3.25, median FIB-4 remained relatively stable but progressed from 1.56 to 1.65 over 5 years.

Conclusion: Progression to cirrhosis over 5 years in co-infected individuals occurred in only a minority of patients and those who progressed to cirrhosis started out with a higher FIB-4 than the non-progressors. Further research will elucidate the predictors of FIB-4 progression and enable the prioritization of patients for whom treatment is more critical.