Contemporary epidemiology of hepatocellular carcinoma: understanding risk factors and surveillance strategies

Abstract

The contemporary epidemiology of hepatocellular carcinoma (HCC) shows a shift in the main etiological risk factors from less common but highly virulent (eg, hepatitis C and B) to more common but weak risk factors (eg, alcohol and metabolic syndrome). Therefore, we are in a seemingly paradoxical state of declining overall incidence rates of HCC-related to improved prevention and treatment of viral hepatitis but burgeoning number of people at an elevated risk of HCC. Several geographic regions have reported an increase in HCC attributable to alcoholic liver disease and metabolic dysfunction associated with steatotic liver disease (MASLD). The importance of risk stratification is increasing to allow for targeted prevention and early detection of HCC. Most risk factors predispose HCC through the formation of cirrhosis, which has served as the main risk stratifying factor. However, this scheme is showing cracks at both ends of the spectrum. On one hand, the risk of developing HCC varies widely among patients with contemporary advanced fibrosis or cirrhosis, and on the other hand up to one-third of MASLD-related HCC occurs among patients with no clear evidence of cirrhosis. The use of multidimensional (eg, clinical, epidemiological, and biochemical) predictive algorithms may improve risk stratification efforts. The shift in HCC risk factors also further heightened the importance and limitations of current surveillance practices (eg, reduced performance of ultrasound in MASLD). Therefore, exploring advanced imaging methods, new biomarkers but also existing combinations of biomarkers augmented by clinical factors for HCC early detection is crucial.