FIB-4 index is associated with hepatocellular carcinoma risk in HIV-infected patients

Abstract

Background: Chronic inflammation caused by hepatitis B virus infection, hepatitis C virus infection, and/or heavy alcohol use can lead to fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). FIB-4 is an index score calculated from platelet count, alanine transaminase, aspartate transaminase, and age that predicts fibrosis and cirrhosis. We hypothesized that high FIB-4 would be associated with development of HCC in HIV-infected persons, who are at high risk due to high prevalence of viral hepatitis and alcohol consumption, and possibly due to HIV infection itself.

Methods: Using proportional hazards models, we tested this hypothesis among 22,980 HIV-infected men from the Veterans Aging Cohort Study. We identified incident HCC cases from the Veterans Affairs Central Cancer Registry.

Results: During follow-up, there were 112 incident HCC diagnoses. The age- and race/ethnic group-adjusted HR was 4.2 [95% confidence interval (CI), 2.4-7.4] for intermediate FIB-4 and 13.0 (95% CI, 7.2-23.4) for high FIB-4, compared with low FIB-4. After further adjustment for enrollment year, CD4 count, HIV-1 RNA level, antiretroviral therapy use, hepatitis B and C virus infection, alcohol abuse/dependency, and diabetes, FIB-4 remained a strong, significant, independent risk factor for HCC. The multivariate-adjusted HR was 3.6 (95% CI, 2.1-6.4) for intermediate FIB-4 and 9.6 (95% CI, 5.2-17.4) for high FIB-4.

Conclusions: Calculated from routine, noninvasive laboratory tests, FIB-4 is a strong, independent HCC risk factor in HIV-infected patients.

Impact: FIB-4 might prove valuable as an easily measured index to identify those at highest risk for HCC, even prior to development of clinical cirrhosis.

Figure 1

Kaplan-Meier cumulative incidence function: time to incident hepatocellular carcinoma (HCC) by FIB-4 category. Kaplan-Meier cumulative incidence curves display time to incident HCC diagnoses, stratified by FIB-4 category (low, intermediate, and high). To reduce the possibility of reverse causality, follow-up time began one year after baseline. Therefore, time 0 on the x-axis is equivalent to one year post-baseline.