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J Clin Oncol. 2019 Feb 1;37(4):296-304. doi: 10.1200/JCO.18.00885. Epub 2018 Dec 18.

Influence of HIV Infection on the Natural History of Hepatocellular Carcinoma: Results From a Global Multicohort Study.

Author information

1
1 Imperial College London, London, United Kingdom.
2
2 University of Cambridge, Cambridge, United Kingdom.
3
3 VA Central Texas Health Care System, Austin, TX.
4
4 Università di Bologna, Bologna, Italy.
5
5 Hospital Universitario Vall d'Hebron, Vall d'Hebron Institut of Research, CIBERehd, Universitat Autonoma de Barcelona, Barcelona, Spain.
6
6 St. Paul's Hospital, Vancouver, British Columbia, Canada.
7
7 Chelsea and Westminster Hospital and Imperial College London, London, United Kingdom.
8
8 Universidad de Sevilla, Seville, Spain.
9
9 Merck Sharp & Dohme, Kenilworth, NJ.
10
10 University of Texas Southwestern Medical Center, Dallas, TX.
11
11 Ospedale Belcolle, Viterbo, Italy.
12
12 Universidade de São Paulo, São Paulo-SP, Brazil.
13
13 Università di Padova, Padova, Italy.
14
14 Policlinico Universitario A. Gemelli, Rome, Italy.
15
15 VA New York Harbor Healthcare System, Brooklyn, NY.
16
16 Columbia University, New York, NY.
17
17 Singapore General Hospital, Singapore.
18
18 Università di Genova, Genova, Italy.
19
19 James J. Peters Veterans Affairs Medical Center, Bronx, NY.
20
20 Icahn School Medicine at Mount Sinai, New York, NY.

Abstract

PURPOSE:

Conflicting evidence indicates that HIV seropositivity may influence the outcome of patients with hepatocellular carcinoma (HCC), a leading cause of mortality in people with HIV. We aimed to verify whether HIV affected the overall survival (OS) of patients with HCC, independent of treatment and geographic origin.

PATIENTS AND METHODS:

We designed an international multicohort study of patients with HCC accrued from four continents who did not receive any anticancer treatment. We estimated the effect of HIV seropositivity on patients' OS while accounting for common prognostic factors and demographic characteristics in uni- and multivariable models.

RESULTS:

A total of 1,588 patients were recruited, 132 of whom were HIV positive. Most patients clustered within Barcelona Clinic Liver Cancer (BCLC) C or D criteria (n = 1,168 [74%]) and Child-Turcotte-Pugh (CTP) class B (median score, 7; interquartile range [IQR], 3). At HCC diagnosis, the majority of patients who were HIV-positive (n = 65 [64%]) had been on antiretrovirals for a median duration of 8.3 years (IQR, 8.59 years) and had median CD4+ cell counts of 256 (IQR, 284) with undetectable HIV RNA (n = 68 [52%]). OS decreased significantly throughout BCLC stages 0 to D (16, 12, 7.5, 3.1, and 3 months, respectively; P < .001). Median OS of patients who were HIV-positive was one half that of their HIV-uninfected counterparts (2.2 months [bootstrap 95% CI, 1.2 to 3.1 months] v 4.1 months [95% CI, 3.6 to 4.4 months]). In adjusted analyses, HIV seropositivity increased the hazard of death by 24% ( P = .0333) independent of BCLC ( P < .0001), CTP ( P < .0001), α-fetoprotein ( P < .0001), geographical origin ( P < .0001), and male sex ( P = .0016). Predictors of worse OS in patients who were HIV-positive included CTP ( P = .0071) and α-fetoprotein ( P < .0001).

CONCLUSION:

Despite adequate antiretroviral treatment, HIV seropositivity is associated with decreased survival in HCC, independent of stage, anticancer treatment, and geographical origin. Mechanistic studies investigating the immunobiology of HIV-associated HCC are urgently required.

PMID:
30562130
DOI:
10.1200/JCO.18.00885

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