Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis

J Hepatol. 2018 Dec;69(6):1274-1283. doi: 10.1016/j.jhep.2018.07.022. Epub 2018 Aug 6.


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.

Keywords: Alcoholic liver disease; Compensated cirrhosis; Competing risk analysis; HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Bilirubin / blood
  • Biopsy
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / etiology*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Liver / pathology
  • Liver Cirrhosis, Alcoholic / complications*
  • Liver Cirrhosis, Alcoholic / mortality
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / etiology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Progression-Free Survival
  • Prospective Studies
  • Prothrombin / analysis
  • Risk Factors
  • Sex Factors
  • alpha-Fetoproteins / analysis


  • alpha-Fetoproteins
  • Prothrombin
  • Bilirubin