Abstract 4308: Multiplicative interaction between HIV infection status and FIB-4 in prediction of hepatocellular carcinoma risk
Authors: Park Lesley S. , Tate Janet P. , Lo Re Vincent , Butt Adeel A. , Gibert Cynthia , Goetz Matthew Bidwell , Brown Sheldon T. , Lim Joseph , Rimland David , Lee Jennifer S. , Justice Amy C. , Dubrow Robert 
Published: July 2016

Abstract
Purpose: FIB-4 is an established marker of liver fibrosis and cirrhosis, calculated from platelet count, alanine transaminase, aspartate transaminase, and age. We previously found baseline FIB-4 to be strongly associated with hepatocellular carcinoma (HCC) risk among HIV-infected (HIV+) patients in the US; a similar finding was reported among persons who consume alcohol or are chronic hepatitis B virus (HBV) carriers in South Korea. Longitudinal associations between FIB-4 and HCC risk have not yet been explored. We aimed to expand our prior investigation by including uninfected patients, using time-updated FIB-4, and testing for multiplicative interaction between HIV status and FIB-4 in the prediction of HCC risk. We hypothesized that the relationship between FIB-4 and HCC risk would differ by HIV status.
Methods: We tested this hypothesis in the Veterans Aging Cohort Study, an open cohort that enrolls HIV+ veterans when they begin HIV care in the Veterans Health Administration and matches two uninfected patients by age, sex, race/ethnicity, and clinical site. We used proportional hazards regression models with time-varying covariates to calculate hazard ratios (HR) and 95% confidence intervals (CI) for FIB-4, adjusted for HCC risk factors (age, sex, race, hepatitis C virus (HCV) infection, HBV infection, smoking, alcohol, BMI, and diabetes). We used the counting process to create time-updated FIB-4 intervals and examined one-, three-, and five-year lagged FIB-4. We identified incident HCC cases from the VA Central Cancer Registry and determined hepatitis C virus and hepatitis B virus status from laboratory results. We defined low (3.25) as previously established.
Results: Between 2000 and 2012, among 37,158 HIV+ subjects, 202 developed HCC. Among 78,339 uninfected subjects, 207 developed HCC. There was a significant multiplicative interaction between HIV status and one-year lagged FIB-4 (interaction p = 0.0015). High FIB-4 was a stronger predictor of HCC in the uninfected than in HIV+. Among uninfected, the adjusted HR was 6.9 (95% CI: 3.4, 12.5) for intermediate FIB-4 and 40.0 (95% CI: 22.3, 71.8) for high FIB-4 compared to uninfected with low FIB-4. Among HIV+, with the same reference group (uninfected with low FIB-4), the adjusted HR was 2.1 (95% CI: 1.0, 4.4) for low FIB-4, 6.4 (95% CI: 3.5, 11.7) for intermediate FIB-4, and 23.7 (95% CI: 13.1, 42.9) for high FIB-4. There was no interaction between FIB-4 and HCV status (p = 0.92). Results were qualitatively similar using a three- or five-year lag.
Conclusions: Calculated from routine, non-invasive laboratory tests, FIB-4 is a strong, independent HCC risk factor in both HIV+ and uninfected subjects after adjustment for other HCC risk factors. FiB-4 appears to be a stronger risk factor in uninfected than in HIV+.
Citation Format: Lesley S. Park, Janet P. Tate, Vincent Lo Re, Adeel A. Butt, Cynthia Gibert, Matthew Bidwell Goetz, Sheldon T. Brown, Joseph Lim, David Rimland, Jennifer S. Lee, Amy C. Justice, Robert Dubrow. Multiplicative interaction between HIV infection status and FIB-4 in prediction of hepatocellular carcinoma risk. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4308.