Hepatocellular carcinoma (HCC) is the second most common cause for cancer related death in the world, with an estimated 750,000 new cases and 695,000 deaths per year. WHO estimate that HCC is responsible for around 47,000 deaths per year in Europe. HCC develops from chronic and progressive liver injury that arises via an array of insults to the liver including obesity associated non-steatohepatitis (NASH); alcohol-related steatohepatitis (ASH), chronic hepatitis B and C virus (HBV/HCV) infection. These co-morbidities impact on both diagnosis and treatment response, however, they are not currently considered in patient management guidelines. Recent health economic studies in Europe have estimated the incidence and mortality rates of HCC of 65,000 and 60,240 cases. In almost all populations, males have higher liver cancer rates than females, with male:female ratios usually averaging between 2:1 and 4:1. Given prevailing demographic and life expectancy trends, the number of HCC patients is expected to be as many as 78,000 in 2020. Studies indicate that the number of HCC related hospitalizations are increasing compared with two decades ago, causing significant direct costs. Thus, HCC is a cause of a significant and increasing overall burden for health systems and society overall and the increasing number of individuals with HCC may have major public health and economic implications.
Given the limited efficacy of current treatments and the huge social implications of HCC progression, this highlights the urgent need to define common and co-morbidity specific pathways and associated bio-markers for patient stratification to improve diagnosis and therapy. The HEP-CAR consortium aimed to extend and integrate the pathophysiological knowledge on HCC to determine the impact of co-morbidities on the prevention, diagnosis and treatment of HCC. Our goal was to develop and validate informed management strategies based on the major co-morbidities associated with HCC progression in the European population. HEP-CAR employed the multidisciplinary skills of selected European partners with expertise in liver disease and who have well characterised HCC cohorts and excellent resources to address the objectives of the project.
The summary of achievements regarding the overall HEP-CAR objectives are summarised below:
• Define host pathways associated with HCC co-morbidities including non-alcoholic steatohepatitis (NASH), chronic hepatitis B and C virus (HBV/HCV) infections. In general we found host pathways altered in HCC independent of the co-morbidity as well as co-morbidity-specific alterations
• Develop clinical tools that will personalize prevention and treatment of HCC patients. We identified phosphopeptides as novel HCC-associated antigens recognized by CD8+ T cells that may emerge as a promising novel tool in personalized HCC treatment expecially since the phosphoproteome is affected by co-morbidity.
• Guide future strategies to prevent, diagnose, and treat HCC in Europe. We made several steps to deliver new data relevant for HCC classification and treatment
Taken together, the obtained results have clearly paved the way for translational exploitation.
