Differences between hepatocellular carcinoma caused by alcohol and other aetiologies

Alcohol-related liver disease is the third leading cause of hepatocellular carcinoma worldwide and the leading cause in Europe. Additionally, the recent definition of metabolic dysfunction-associated steatotic liver disease with increased alcohol intake (MetALD) will enrich this population with a more nuanced phenotype, reflecting recent epidemiological trends. In these patients, the hepatocellular carcinoma diagnosis is often delayed and less frequently detected through screening programmes. Moreover, at the time of diagnosis, patients with alcohol-related hepatocellular carcinoma tend to have a poorer general condition, more severely impaired liver function, and a higher prevalence of comorbidities, leading to increased competitive mortality. However, when hepatocellular carcinoma is diagnosed during surveillance programmes in patients with alcohol-related liver disease or MetALD, the rate of allocation to first-line curative treatments is high (56%) and comparable to that of patients with virus-related hepatocellular carcinoma. As a consequence, the aetiology of the underlying cirrhosis cannot be considered an independent prognostic factor in patients with hepatocellular carcinoma. Instead, prognosis is driven by liver function, general condition, and tumour burden. This underscores the crucial role of early diagnosis through periodic surveillance in patients with alcohol- or MetALD-related cirrhosis.