Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis
Author(s): ,
Sylvie Chevret
Affiliations:
SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France
,
Michel Beaugrand
Affiliations:
AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
,
Jean-Pierre Zarski
Affiliations:
Clinique d’hépato-gastroentérologie pôle Digidune CHU de Grenoble, France
,
Xavier Amiot
Affiliations:
Liver Unit, APHP, CHU Tenon, Paris, France
,
Gabriel Perlemuter
Affiliations:
Liver Unit, University Hospital, Béclère, APHP, Clamart, France
,
Albert Tran
Affiliations:
University Hospital of Nice, Digestive Centre, Nice F-06202, Cedex 3, France
,
Jean-Marie Péron
Affiliations:
Liver Unit, Universitary Hospital Purpan, University Paul Sabatier III, Toulouse, France
,
Jean Henrion
Affiliations:
Liver Unit, University Hospital, Haine Saint-Paul, Belgium
,
Violaine Ozenne
Affiliations:
Liver Unit, APHP, CHU Lariboisière, Paris, France
,
Victor de Ledinghen
Affiliations:
Hepatology Unit, University Hospital, CHU Bordeaux, France
,
Stanislas Pol
Affiliations:
Université Paris Descartes, APHP, Liver Unit, Hôpital Cochin, INSERM U1223, Institut Pasteur, Paris, France
,
Térésa Antonini
Affiliations:
Liver Unit, APHP, CHU Paul Brousse, Villejuif, France
,
Nicolas Carbonell
Affiliations:
Liver Unit, APHP, CHU Saint-Antoine, Paris, France
,
Eric Nguyen-Khac
Affiliations:
Liver Unit, University Hospital, Amiens, France
,
Odile Goria
Affiliations:
Liver Unit, University Hospital, Rouen, France
,
Romain Moirand
Affiliations:
Univ Rennes, INSERM, INRA, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), F-35000 Rennes, France
,
Thông Dao
Affiliations:
Liver Unit, University Hospital, Caen, France
,
Alexandre Louvet
Affiliations:
Liver Unit, University Hospital, Lille, France
,
Christophe Moreno
Affiliations:
Liver Unit, CUB Hôpital Erasme, Université Libre de Bruxelles, Belgium
,
Dominique Roulot
Affiliations:
Liver Unit, APHP, Avicenne, Bobigny, France
,
Frédéric Oberti
Affiliations:
Liver Unit, University Hospital, Angers, France
,
Jean-Marc Perarnau
Affiliations:
Liver Unit, University Hospital, Tours, France
,
Isabelle Archambeaud
Affiliations:
Liver Unit, CHU, Nantes, France
,
Valérie Bourcier
Affiliations:
AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
,
Cendrine Chaffaut
Affiliations:
SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France
Nathalie Ganne-Carrié
Affiliations:
Inserm, UMR-1162 « Functional Genomics of Solid Tumors », F-75010 Paris, France
Corresponding author. Address: AP-HP, Hôpital Jean Verdier, Liver Unit, Avenue du 14 Juillet, Bondy, France; Tel.: +33 148026294.
EASL LiverTree™. Ganne-Carrié N. Dec 1, 2018; 256768
Nathalie Ganne-Carrié
Nathalie Ganne-Carrié

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Graphical abstract

Graphical abstract

HCC annual incidence is 2.9%, emphazising the need for its screening in alcoholic cirrhosis. Independent risk factors for HCC are age, male gender, baseline AFP and surrogate markers of minimal liver failure. Only 56% of the patients diagnosed with HCC underwent a curative treatment. The main reasons not to treat were liver failure and/or impaired general status at diagnosis. Increased use of radiological ablative therapies for patients with alcoholic cirrhosis is needed.

Background & Aims

More than 90% of cases of hepatocellular carcinoma (HCC) occur in patients with cirrhosis, of which alcohol is a major cause. The CIRRAL cohort aimed to assess the burden of complications in patients with alcoholic cirrhosis, particularly the occurrence of HCC.

Methods

Patients with biopsy-proven compensated alcoholic cirrhosis were included then prospectively followed. The main endpoint was the incidence of HCC. Secondary outcomes were incidence of hepatic focal lesions, overall survival (OS), liver-related mortality and event-free survival (EFS).

Results

From October 2010 to April 2016, 652 patients were included in 22 French and Belgian centers. During follow-up (median 29 months), HCC was diagnosed in 43 patients. With the limitation derived from the uncertainty of consecutive patients’ inclusion and from a sizable proportion of dropouts (153/652), the incidence of HCC was 2.9 per 100 patient-years, and one- and two-year cumulative incidences of 1.8% and 5.2%, respectively. Although HCC fulfilled the Milan criteria in 33 cases (77%), only 24 patients (56%) underwent curative treatment. An explorative prognostic analysis showed that age, male gender, baseline alpha-fetoprotein, bilirubin and prothrombin were significantly associated with the risk of HCC occurrence. Among 73 deaths, 61 had a recorded cause and 27 were directly attributable to liver disease. At two years, OS, EFS and cumulative incidences of liver-related deaths were 93% (95% CI 90.5–95.4), 80.3% (95% CI 76.9–83.9), and 3.2% (95% CI 1.6–4.8) respectively.

Conclusion

This large prospective cohort incompletely representative of the whole population with alcoholic cirrhosis showed: a) an annual incidence of HCC of up to 2.9 per 100 patient-years, suggesting that surveillance might be cost effective in these patients; b) a high proportion of HCC detected within the Milan criteria, but only one-half of detected HCC cases were referred for curative treatments; c) a two-year mortality rate of up to 7%.

Lay summary

Cirrhosis is a risk factor for primary liver cancer, leading to recommendations for periodic screening. However, for alcohol-related liver disease the rational of periodic screening for hepatocellular carcinoma (HCC) is controversial, as registry and databased studies have suggested a low incidence of HCC in these patients and highly competitive mortality rates. In this study, a large cohort of patients with biopsy-proven alcoholic cirrhosis prospectively screened for HCC demonstrated a high annual incidence of HCC (2.9%) and a high percentage of small cancers theoretically eligible for curative treatment. This suggests that patients with liver disease related to alcohol should not be ruled out of screening.

Keyword(s)
Alcoholic liver disease, Compensated cirrhosis, HCC, Competing risk analysis
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