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Fibrosis, CD4 Count Predict Liver-Related Death in HIV/HCV Patients

June 18, 2015

Fibrosis stage 2 or higher and lower CD4 count independently predicted liver-related mortality in a 3,941-person analysis of EuroSIDA cohort members with HIV and hepatitis C (HCV) coinfection. Five-year probability of liver-related death exceeded 10% in people with F2 or worse fibrosis.

Direct-acting antiretrovirals (DAAs) pushed HCV cure rates above 90% in clinical trials enrolling people with and without HIV. Because these new drugs are expensive, clinicians seek guidance in selecting patients who need them most. To address that question, EuroSIDA investigators analyzed cohort members coinfected with HIV and HCV and in follow-up starting Jan. 1, 2000. They classified causes of death by Coding causes of Death in HIV (CoDe) methodology and used competing-risk Cox proportional-hazards models to identify factors associated with liver-related death, calculated as subdistribution hazard ratios (sHR).

The study, which was published in the journal AIDS, included 3,941 HIV/HCV-coinfected EuroSIDA members, 94% of them white, 68% men and 70% who became infected with HIV while injecting drugs. During a median 3.5 years of follow-up, 670 people died for a crude mortality of 41.6 per 1000 person-years. Liver-related death accounted for 21.6% of deaths (9.0 per 1000 person-years), exceeded only by AIDS, which accounted for 24.2% of deaths.

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All-cause mortality and nonliver deaths peaked in people 55 and older, whereas liver-related deaths occurred most often in people 35 to 55. Those with F4 fibrosis had a 35-fold higher liver death rate when compared with cohort members who had F0 or F1 fibrosis at the baseline visit, and an 8-fold higher rate when compared with those with F2/3 fibrosis. F4 fibrosis was linked to a 6-fold higher liver-related death risk than F0/1 fibrosis (sHR: 6.25, 95% confidence interval [CI]: 4.08 to 9.58, P < .0001), while F2/3 fibrosis conferred a 2.5-fold higher liver death risk (sHR: 2.52, 95% CI: 1.53 to 4.15, P < .0001).

This Cox analysis linked every twice-higher baseline CD4 count to more than a 15% lower risk of liver death (sHR: 0.83, 95% CI: 0.73 to 0.95, P = .0052). Other factors independently associated with liver-related death were being age 35 to 45 versus under 35 (sHR: 1.61, 95% CI: 1.01 to 2.57, P = .045), positive hepatitis B surface antigen (sHR: 2.15, 95% CI: 1.31 to 3.51, P = .0024), and being HCV-antibody positive for more than 10 years versus fewer than two years (sHR: 1.95, 95% CI: 1.03 to 3.71, P = .041).

Five-year probability of liver-related death jumped from 2.2% in people with baseline F0/1 fibrosis to 10.3% in those with F2/3 fibrosis and to 14% in those with F4 fibrosis.

On the basis of these findings, the EuroSIDA team proposed that DAAs should be prioritized for people with at least F2 fibrosis. Starting antiretroviral therapy early enough to avoid low CD4 counts, they argued, "should be considered essential to decrease the risk of liver-related death and the need for HCV treatment."

Mark Mascolini is a freelance writer focused on HIV infection.


Copyright © 2015 Remedy Health Media, LLC. All rights reserved.




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