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J Hepatol. 2019 Apr 6. pii: S0168-8278(19)30226-0. doi: 10.1016/j.jhep.2019.03.032. [Epub ahead of print]

Incidence of hepatocellular carcinoma in HIV/HBV-coinfected patients on tenofovir therapy: Relevance for screening strategies.

Author information

1
Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Switzerland. Electronic address: gilles.wandeler@insel.ch.
2
Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland.
3
University Clinic for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Switzerland.
4
Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland; Department of Mathematics and Statistics, Masaryk University, Brno, Czech Republic.
5
HIV Monitoring Foundation, Amsterdam, the Netherlands; Department of Global Health, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands; Division of Infectious Diseases, Amsterdam University Medical Centers, Location AMC, the Netherlands.
6
CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
7
ISPED, Université Bordeaux, Centre INSERM U1219-Epidémiologie Biostatistique, France.
8
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Switzerland; Department of Public Health, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
9
Division of Infectious Diseases, Regional Hospital Lugano, Switzerland.
10
Division of Infectious Diseases, Amsterdam University Medical Centers, Location AMC, the Netherlands.
11
HIV Monitoring Foundation, Amsterdam, the Netherlands.
12
Department of Medicine I, University Hospital Bonn, Bonn, Germany.
13
CHU de Bordeaux, Service de Maladies Infectieuses et Tropicales, Bordeaux, France.
14
ISPED, Université Bordeaux, Centre INSERM U1219-Epidémiologie Biostatistique, France; CHU Bordeaux, Service de Médecine Interne et Maladies Infectieuses, Bordeaux, France.

Abstract

BACKGROUND & AIMS:

Robust data on hepatocellular carcinoma (HCC) incidence among HIV/hepatitis B virus (HBV)-coinfected individuals on antiretroviral therapy (ART) are needed to inform HCC screening strategies. We aimed to evaluate the incidence and risk factors of HCC among HIV/HBV-coinfected individuals on tenofovir disoproxil fumarate (TDF)-containing ART in a large multi-cohort study.

METHODS:

We included all HIV-infected adults with a positive hepatitis B surface antigen test followed in 4 prospective European cohorts. The primary outcome was the occurrence of HCC. Demographic and clinical information was retrieved from routinely collected data, and liver cirrhosis was defined according to results from liver biopsy or non-invasive measurements. Multivariable Poisson regression was used to assess HCC risk factors.

RESULTS:

A total of 3,625 HIV/HBV-coinfected patients were included, of whom 72% had started TDF-containing ART. Over 32,673 patient-years (py), 60 individuals (1.7%) developed an HCC. The incidence of HCC remained stable over time among individuals on TDF, whereas it increased steadily among those not on TDF. Among individuals on TDF, the incidence of HCC was 5.9 per 1,000 py (95% CI 3.60-9.10) in cirrhotics and 1.17 per 1,000 py (0.56-2.14) among non-cirrhotics. Age at initiation of TDF (adjusted incidence rate ratio per 10-year increase: 2.2, 95% CI 1.6-3.0) and the presence of liver cirrhosis (4.5, 2.3-8.9) were predictors of HCC. Among non-cirrhotic individuals, the incidence of HCC was only above the commonly used screening threshold of 2 cases per 1,000 py in patients aged >45 years old at TDF initiation.

CONCLUSIONS:

Whereas the incidence of HCC was high in cirrhotic HIV/HBV-coinfected individuals, it remained below the HCC screening threshold in patients without cirrhosis who started TDF aged <46 years old.

LAY SUMMARY:

We investigated the incidence of hepatocellular carcinoma in HIV/hepatitis B virus-coinfected individuals from a large multi-cohort study in Europe. Over 32,673 patient-years, 60 individuals (1.7%) developed hepatocellular carcinoma. The incidence of hepatocellular carcinoma remained low in patients without cirrhosis, who started on tenofovir disoproxil fumarate when aged <46 years old.

KEYWORDS:

Antiretroviral; HIV infection; Hepatitis B infection; Hepatocellular carcinoma; Nucleotide inhibitors; Screening; Surveillance

PMID:
30965070
DOI:
10.1016/j.jhep.2019.03.032

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