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  Conference on Retroviruses
and Opportunistic Infections
Seattle, Washington
March 4-7, 2019
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Higher HIV load, lower CD4s predict liver
cancer without advanced fibrosis
  Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2019, Seattle
Mark Mascolini
A higher HIV load and lower CD4 count contribute to liver cancer risk without advanced fibrosis, according to results of a longitudinal study in more than 32,000 veterans with HIV [1]. A sustained HIV load above 500 copies also emerged as an independent liver cancer predictor.
Veterans Aging Cohort Study (VACS) researchers noted that hepatocellular carcinoma (HCC) incidence (the new-diagnosis rate) has quadrupled since 1996 in people with HIV. HCC risk stands 4-fold higher in people with than without HIV, but drivers of this disparity remain unclear.
VACS maintains electronic medical records for HIV-positive veterans across the United States. The Veterans Administration keeps a cancer registry that records HCC cases confirmed by x-ray or pathology. This analysis included HIV-positive veterans with HIV RNA (viral load) and CD4 count assessed between October 1999 and September 2015. All participants had at least 180 days of observation after the initial lab assessment. The study excluded veterans who had HCC before starting follow-up in this analysis. Follow-up continued until HCC diagnosis, death, last VA visit, or September 30, 2015. The investigators defined advanced fibrosis/cirrhosis as a FIB-4 score above 3.25.
The study involved 2497 veterans with a baseline FIB-4 above 3.25 and 29,836 with a lower FIB-4. Median FIB-4 stood at 4.73 in the higher group and 1.12 in the lower group. Almost all veterans in both groups (98% and 97%) were men, and 49% and 47% were black. Median age was higher in the high FIB-4 group (50 versus 46), and the high FIB-4 group had a higher proportion with alcohol abuse (47% versus 29%), hepatitis B surface antigen (HBsAg) (10% versus 5%), HIV RNA at or above 500 copies (63% versus 56%), and CD4 count below 200 (39% versus 26%). Among 278 of these HIV-positive veterans diagnosed with HCC, 43% had a FIB-4 below 3.25, indicating lack of advanced fibrosis.
Cox regression analysis to identify independent predictors of HCC determined that each 10-fold higher HIV load boosted HCC risk in veterans with a FIB-4 below 3.25 (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.09 to 1.41) but not in those with a FIB-4 above 3.25. Similarly, more than 12 months with an HIV load above 500 copies independently boosted HCC risk in the lower FIB-4 group (HR 1.57, 95% CI 1.03 to 2.37) but not in the higher FIB-4 group.
In the same way CD4 measures did not predict HCC in veterans with FIB-4 above 3.25 but did in those with lower FIB-4 (CD4 below 200: HR 1.58, 95% CI 1.01 to 2.46, in the Cox model based on 10-fold higher HIV loads; HR 1.78, 95% CI 1.16 to 2.74, in the Cox model based on consecutive months with HIV load above 500 copies).
HCV coinfection and HBsAg positivity independently predicted HCC in the high and low FIB-4 groups and in both Cox models.
The VACS team stressed that in this group of HIV-positive veterans diagnosed with HCC, 43% had a FIB-4 below 3.25. In the general population, only 13% of HCC diagnoses arise in people with a sub-3.25 FIB-4. The investigators proposed that HCC risk factors in HIV-positive people vary by baseline risk factors: HBV or HCV coinfection boosted HCC risk in both lower and higher FIB-4 groups. But high HIV load and low CD4 count predicted HCC only in those with a FIB-4 below 3.25.
1. Torgersen J, Kallan MJ, Carbonari DM, et al. HIV viremia and low CD4+ increase HCC risk in those without advanced liver fibrosis. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 90.