Gender Disparities in Hepatocellular Carcinoma Incidence Among 40 Years and Above Age Groups: Need for a Targeted Intervention?

Introduction: Hepatocellular carcinoma is a leading cause of mortality in patients with cirrhosis, with risk factors of hepatitis virus, alcohol intake, diabetes, or obesity-related NASH. It rarely occurs before the age of 40 years. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database using 17 registries to identify hepatocellular carcinoma (HCC) cases among patients of age 40 and above from 2000 to 2019. We calculated the annual percentage change (APC) of HCC diagnosis using joinpoint regression, stratified by age based on the 2000 US standard population. Results: We included a total of 121,746 cases of HCC of age 40 and above. The incident cases were almost 3 times more predominant among males (90,136 vs 31,610), with the highest incident cases in the 60-64 years age group. The age-adjusted incidence rate of HCC among patients 40 and above is 16.2 per 100,000 (male vs female: 25.8 vs 7.8 per 100,000), being highest among patients of the 80-85 years age group. The age of diagnosis percentage change increased at a higher rate until 55-60 years of age with being rate higher among males (17.5 (11.7-22.3) vs 12.9 (7.9 – 26.1)), which later increased but at a slower rate (0.7 (-0.7 – 1.6) vs 2.3 (0.2 – 4.1)). The APC for both genders increased from 2000 until 2014/2015 (male: 4.8 (4.3 – 5.6) from 2000-2008, 1.6 (1.9 – 2.2) from 2008-2015, female: 2.8 (2.3 – 3.6) from 2000-2014), which decreased from 2014/2015 until 2019 with APC of -3.1 (-4.4 to -2.0) in males versus -2.1 (-5.4 to -0.3) in females (Figure 1). Conclusion: Our study revealed a significant gender disparity in HCC incidence, with males accounting for nearly 3 times the number of incident cases compared to females. The highest incidence cases occurred in 60-64 years age group, emphasizing the need for targeted intervention in this population. The annual percent change analysis demonstrated an increasing trend in HCC incidence for both genders until 2014/2015, followed by a subsequent decrease. We need to investigate to understand the factors underlying these trends and inform the preventative strategies.Figure 1.: Gender variation of age-adjusted incidence rate of hepatocellular carcinoma with year of diagnosis.