Nathalie Ganne-Carrié1, Cendrine Chaffaut2, Valérie Bourcier3, Isabelle Archambeaud4, Jean-Marc Perarnau5, Frédéric Oberti6, Dominique Roulot7, Christophe Moreno8, Alexandre Louvet9, Thông Dao10, Romain Moirand11, Odile Goria12, Eric Nguyen-Khac13, Nicolas Carbonell14, Térésa Antonini15, Stanislas Pol16, Victor de Ledinghen17, Violaine Ozenne18, Jean Henrion19, Jean-Marie Péron20, Albert Tran21, Gabriel Perlemuter22, Xavier Amiot23, Jean-Pierre Zarski24, Michel Beaugrand3, Sylvie Chevret2. 1. AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France; University Paris 13, Sorbonne Paris Cité, "équipe labellisée Ligue Contre le Cancer" F-93000 Bobigny, France; Inserm, UMR-1162 « Functional Genomics of Solid Tumors », F-75010 Paris, France. Electronic address: nathalie.ganne@jvr.aphp.fr. 2. SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France. 3. AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France. 4. Liver Unit, CHU, Nantes, France. 5. Liver Unit, University Hospital, Tours, France. 6. Liver Unit, University Hospital, Angers, France. 7. University Paris 13, Sorbonne Paris Cité, "équipe labellisée Ligue Contre le Cancer" F-93000 Bobigny, France; Liver Unit, APHP, Avicenne, Bobigny, France. 8. Liver Unit, CUB Hôpital Erasme, Université Libre de Bruxelles, Belgium. 9. Liver Unit, University Hospital, Lille, France. 10. Liver Unit, University Hospital, Caen, France. 11. Univ Rennes, INSERM, INRA, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), F-35000 Rennes, France. 12. Liver Unit, University Hospital, Rouen, France. 13. Liver Unit, University Hospital, Amiens, France. 14. Liver Unit, APHP, CHU Saint-Antoine, Paris, France. 15. Liver Unit, APHP, CHU Paul Brousse, Villejuif, France. 16. Université Paris Descartes, APHP, Liver Unit, Hôpital Cochin, INSERM U1223, Institut Pasteur, Paris, France. 17. Hepatology Unit, University Hospital, CHU Bordeaux, France. 18. Liver Unit, APHP, CHU Lariboisière, Paris, France. 19. Liver Unit, University Hospital, Haine Saint-Paul, Belgium. 20. Liver Unit, Universitary Hospital Purpan, University Paul Sabatier III, Toulouse, France. 21. Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice F-06204, Cedex 3, France; University Hospital of Nice, Digestive Centre, Nice F-06202, Cedex 3, France. 22. Liver Unit, University Hospital, Béclère, APHP, Clamart, France. 23. Liver Unit, APHP, CHU Tenon, Paris, France. 24. Clinique d'hépato-gastroentérologie pôle Digidune CHU de Grenoble, France.
Abstract
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.
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.
Authors: Fasiha Kanwal; Saira Khaderi; Amit G Singal; Jorge A Marrero; Nicole Loo; Sumeet K Asrani; Christopher I Amos; Aaron P Thrift; Xiangjun Gu; Michelle Luster; Abeer Al-Sarraj; Jing Ning; Hashem B El-Serag Journal: Hepatology Date: 2022-03-01 Impact factor: 17.298
Authors: Amit G Singal; Yujin Hoshida; David J Pinato; Jorge Marrero; Jean-Charles Nault; Valerie Paradis; Nabihah Tayob; Morris Sherman; Young Suk Lim; Ziding Feng; Anna S Lok; Jo Ann Rinaudo; Sudhir Srivastava; Josep M Llovet; Augusto Villanueva Journal: Gastroenterology Date: 2021-03-09 Impact factor: 33.883