Influence of HIV Infection on the Natural History of Hepatocellular Carcinoma

Results From a Global Multicohort Study

Liver Cancer in HIV and ITA.LI.CA Study Groups

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)296-304
Number of pages9
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number4
DOIs
Publication statusE-pub ahead of print - Dec 18 2018

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HIV Infections
Hepatocellular Carcinoma
HIV
HIV Seropositivity
Survival
Liver Neoplasms
Fetal Proteins
Therapeutics
CD4 Lymphocyte Count
Demography
RNA
Mortality

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Influence of HIV Infection on the Natural History of Hepatocellular Carcinoma : Results From a Global Multicohort Study. / Liver Cancer in HIV and ITA.LI.CA Study Groups.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 4, 18.12.2018, p. 296-304.

Research output: Contribution to journalArticle

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title = "Influence of HIV Infection on the Natural History of Hepatocellular Carcinoma: Results From a Global Multicohort Study",
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.",
author = "{Liver Cancer in HIV and ITA.LI.CA Study Groups} and Pinato, {David J} and Elias Allara and Ting-Yi Chen and Franco Trevisani and Beatriz Minguez and Marco Zoli and Marianne Harris and {Dalla Pria}, Alessia and Nicol{\'a}s Merchante and Heather Platt and Mamta Jain and Eugenio Caturelli and Luciana Kikuchi and Juan Pineda and Mark Nelson and Fabio Farinati and Rapaccini, {Gian Ludovico} and Ayse Aytaman and Michael Yin and Chee-Kiat Tan and Mark Bower and Giannini, {Edoardo G} and Norbert Br{\"a}u",
year = "2018",
month = "12",
day = "18",
doi = "10.1200/JCO.18.00885",
language = "English",
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TY - JOUR

T1 - Influence of HIV Infection on the Natural History of Hepatocellular Carcinoma

T2 - Results From a Global Multicohort Study

AU - Liver Cancer in HIV and ITA.LI.CA Study Groups

AU - Pinato, David J

AU - Allara, Elias

AU - Chen, Ting-Yi

AU - Trevisani, Franco

AU - Minguez, Beatriz

AU - Zoli, Marco

AU - Harris, Marianne

AU - Dalla Pria, Alessia

AU - Merchante, Nicolás

AU - Platt, Heather

AU - Jain, Mamta

AU - Caturelli, Eugenio

AU - Kikuchi, Luciana

AU - Pineda, Juan

AU - Nelson, Mark

AU - Farinati, Fabio

AU - Rapaccini, Gian Ludovico

AU - Aytaman, Ayse

AU - Yin, Michael

AU - Tan, Chee-Kiat

AU - Bower, Mark

AU - Giannini, Edoardo G

AU - Bräu, Norbert

PY - 2018/12/18

Y1 - 2018/12/18

N2 - 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.

AB - 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.

U2 - 10.1200/JCO.18.00885

DO - 10.1200/JCO.18.00885

M3 - Article

VL - 37

SP - 296

EP - 304

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 4

ER -