Risk factors in adolescents and young adults associated with hepatobiliary cancer: A review.

e16332 Background: Incidence of cancer among adolescents and young adults (AYA) ages 15-39 has risen. Hepatobiliary cancers (HBC), including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are exceedingly rare in AYAs. These represent less than 1% of cancers in this age group. Incidence of HBC in AYA, specifically HCC, has risen in recent years. Understanding risk factors for HBC in this population is important for early detection and targeted therapy. We sought to review the evidence regarding risk factors in AYA for developing HBC. Methods: Comprehensive review using PubMed with key words including “Hepatobiliary cancer”, “hepatocellular carcinoma”, “adolescents and young adults”, “cancer development”, and “risk factors”. Relevant articles published over the past ten years (2014-2024) and focused on human populations, excluding animal studies. Study design, population and type of risk factor were used for data synthesis. Findings suggested interplay of various factors contributing to observed uptrend in incidence. Results: Many risk factors are shown to have increased risk for development of HBC in AYAs. Genetic mutations and inherited diseases, such as familial cholangiocarcinoma and glycogen storage disease, have shown to increase risk of HCC and ICC in AYAs. Mutations in TP53 has been suggested to play a role in a subset of younger HCC patients. Gender risk show male-to-female ratio from 2:1 to 4:1 depending on studies. AYAs with diabetes had a 2.5-fold increased risk of developing HCC compared to non-diabetics. Except for Hep B, increased incidence of HCC is observed in patients with chronic liver disease regardless of etiology. Adolescents with non-alcoholic fatty liver disease (NAFLD) are at a 3.3-fold increased risk of developing HCC. Global incidence of other chronic viral hepatitis has increased. Identifiable risk factors in diet such as red and highly processed meats, refined grains and sugars are shown to be associated with increased risk of HCC. Obesity has been a well-established risk factor for NAFLD and HCC in AYAs. Adolescents with a BMI > 95th percentile had a 1.7-fold increased risk of developing HCC compared to those with normal BMI. Low physical activity had a 1.4-fold increased risk of NAFLD. Regular alcohol use has been associated with a 2.1-fold increased risk of HCC in AYAs. Conclusions: HBC, though rare in AYAs, presents a growing challenge due to association with various risk factors. HCC appears to be trending up in AYA. Multifactorial components in lifestyle, genetic and environmental risks are key to early detection and clinical suspicion in a traditionally low risk population. With rising incidence and poor survival outcomes of these known malignancies, there is need for further research on pathogenesis of HBC in AYAs and evaluation of current management. Greater awareness of screening at-risk populations could improve time to diagnosis, treatment, and prognosis.