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J Viral Hepat. 2018 Oct 31. doi: 10.1111/jvh.13029. [Epub ahead of print]

Non-virological factors are drivers of hepatocellular carcinoma in virosuppressed hepatitis B cirrhosis: Results of ANRS CO12 CirVir cohort.

Author information

1
AP-HP, Hôpital Avicenne, Microbiologie Clinique, Bobigny, France.
2
Université Paris 13, Bobigny, France.
3
INSERM U955, Université Paris-Est, Créteil, France.
4
AP-HP, Hôpital Jean-Verdier, Hépatologie, Bondy, France.
5
INSERM U1162, Université Paris 5, Paris, France.
6
Hospices Civils de Lyon, Hépatologie, Lyon, France.
7
INSERM U1052, Université de Lyon, Lyon, France.
8
AP-HP, Hôpital Henri-Mondor, Unité de Recherche Clinique, Université Paris-Est, DHU A-TVB, IMRB- EA 7376, CEpiA (Clinical Epidemiology and Ageing Unit), Créteil, France.
9
APHP, Hôpital Jean-Verdier, Biochimie, Bondy, France.
10
Unit for Basic and Clinical research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENSH), Paris, France.
11
AP-HP, Hôpital Beaujon, Hépatologie, Clichy, France.
12
CHU Pontchaillou, Hépatologie, Rennes, France.
13
AP-HP, Hôpital Avicenne, Hépatologie, Bobigny, France.
14
AP-HP, Hôpital Cochin, Hépatologie, INSERM UMS20 and U1223, Institut Pasteur, Université Paris Descartes, Paris, France.
15
Hôpital Haut-Lévêque, Hépatologie, Bordeaux, France.
16
Hôpital Michallon, Hépatologie, Grenoble, France.
17
CHU, Hépatologie, Angers, France.
18
CHU, Hépatologie, INSERM U1065, Université de Nice-Sophia-Antipolis, Nice, France.
19
Hôpital Purpan, Hépatologie, Toulouse, France.
20
AP-HP, Hôpital Henri-Mondor, Hépatologie, Créteil, France.
21
Hôpital Charles-Nicolle, Hépatologie, Rouen, France.
22
AP-HP, Hôpital Tenon, Hépatologie, Paris, France.
23
Hôpital St-André, Hépatologie, Bordeaux, France.
24
Hôpital Trousseau, Hépatologie, Tours, France.
25
Institut Arnaud-Tzanck, Hépatologie, St-Laurent-du-Var, France.
26
Hôpital Brabois, Hépatologie, Vandoeuvre-les-Nancy, France.
27
Hôpital Claude-Huriez, Hépatologie, Lille, France.
28
Hôpital Saint-Eloi, Hépatologie, Montpellier, France.
29
CHU, Médecine Interne-Pôle Digestif UMR 152, Toulouse, France.
30
AP-HP, Hôpital Paul-Brousse, Hépatologie, Villejuif, France.
31
AP-HP, Hôpital Saint-Antoine, Hépatologie, Paris, France.
32
CHU, Hépatologie, Le Mans, France.
33
Hôpital Saint-Joseph, Hépatologie, Marseille, France.
34
AP-HP, Hôpital Pitié-Salpêtrière, Hépatologie, Paris, France.
35
CHU, Hépatologie, Poitiers, France.
36
Hôpital Général, Hépatologie, Aix-En-Provence, France.
37
Hôpital Foch, Hépatologie, Suresnes, France.
38
Institut Mutualiste Montsouris, Hépatologie, Paris, France.

Abstract

Worldwide, hepatocellular carcinoma (HCC) occurs mainly in Asian patients with hepatitis B virus (HBV) infection. This study aimed to decipher the environmental and virological factors associated with HCC occurrence and validate risk scoring systems in a French multicentre prospective cohort of HBV cirrhotic patients. Patients with biopsy-proven Child-Pugh A viral cirrhosis included in the ANRS CO12 CirVir cohort who were HBsAg(+) without hepatitis C coinfection were selected for: (a) interview through a standardized questionnaire reporting coffee consumption and HCC familial history; (b) HBsAg quantification using baseline and sequential 2-year frozen sera; (c) baseline HBV genotype determination; and (d) assessment of risk factors and applicability of HCC risk scores (Kaplan-Meier analysis, Cox models). Among 317 patients studied (261 men, median age 53 years, past or ongoing antiviral treatment 93.3% and baseline detectable HBV DNA in 88 patients), the baseline and 2-year median HBsAg levels were 810 and 463 IU/mL, respectively. After a median follow-up of 65.2 months, 27 HCC cases were diagnosed (annual incidence: 1.6%). Three factors were independently associated with HCC occurrence: age > 50 years, platelets ≤ 150 × 103 /mm3 and body mass index ≥ 30 kg/m2 . Two out of five risk scores were validated, and the most accurate was PAGE-B at 1 year. Moreover, HCC in patients without maintained virological suppression seems more aggressive and less accessible to curative treatment. In conclusion, in French patients with HBV cirrhosis mostly virally suppressed, independent HCC risk factors were host-related (age, obesity) or linked to the severity of cirrhosis (thrombopenia), and the European PAGE-B score was the most accurate risk score.

KEYWORDS:

ANRS CO12 CirVir; carcinogenesis; prognosis; risk score; viral cirrhosis

PMID:
30380181
DOI:
10.1111/jvh.13029

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