Abstract
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. 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). 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. 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%. 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.
Highlights
Primary liver cancer has a high incidence in Europe, especially in France, which has almost 9000 cases per year [1]
At 2 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. This large prospective cohort incompletely representative of the whole population with alcoholic cirrhosis showed: a) an annual incidence of hepatocellular carcinoma (HCC) up to 2.9 per 100 patients-year, 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 2-year mortality up to 7%
The main result of the Franco-Belgian CIRRAL prospective cohort is the high incidence of HCC in patients with alcoholic cirrhosis (2.9 per 100 patient-year)
Summary
Primary liver cancer has a high incidence in Europe, especially in France, which has almost 9000 cases per year [1]. Precise data are lacking, as France has lost its longstanding European leadership in alcohol consumption, one can speculate that alcoholic cirrhosis is currently the main cause of HCC occurrence in Europe, and it will gain an even more important predominance as alcoholic consumption is on the rise in many countries, while active viral infection is on the decline. A small but very homogeneous, Spanish cohort of patients with alcoholic cirrhosis prospectively followed for HCC occurrence showed a high incidence of HCC (up to 2.6% per year) [10], which suggests that the implementation of a surveillance program for the early diagnosis of HCC is warranted in these patients
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