Cholangiocarcinoma is an uncommon biliary tract cancer, accounting for 3% of gastrointestinal cancers. It is the second most common type of liver cancer. It can occur anywhere along the biliary tree, and most commonly occurs at the hepatic duct bifurcation. It is categorized as extrahepatic cholangiocarcinoma (ECC) or intrahepatic cholangiocarcinoma (IHCC). In the United States, IHCC incidence has risen over the past 30 years due to its risk factors, including parasitic infections (e.g., liver flukes), chronic liver diseases (e.g., hepatitis B and C, biliary disease), lifestyle factors (e.g., alcohol use, tobacco use, obesity), and genetic predisposition. Previous studies did not explain how demographic characteristics of IHCC patients relate to mortality rates among U.S. populations.
A recent descriptive study published in the medtigo Journal of Medicine aimed to analyze IHCC-related mortality trends in U.S. adults aged >25 years from 1990 to 2020 with a specific focus on contributing demographic factors. The data were collected from the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiology Research (WONDER) database. All data were evaluated by using various factors such as year, age, gender, region, race/ethnicity, place of death, and urban-rural classification. Mortality rates were determined as age-adjusted mortality rates (AAMR) and crude rates. Trends were analyzed using the Jointpoint regression method to calculate the annual percentage change (APC) with significance at P < 0.05.
A total of 113,350 U.S. adults aged >25 years had died due to IHCC between 1999 and 2020. AAMR doubled from 1.4 to 2.8 per 100,000 with an average annual increase of 3.55% (95% confidence interval [CI]: 3.34-3.72). This indicated a consistent upward trend in IHCC mortality over time.  IHCC mortality increased across all age groups except the 25-34 group (Steady crude mortality rate = 0.1, APC = 0.01%, 95% CI: –0.92 to 0.96). Adults aged 55-64 years showed the highest crude mortality rate of 1.8-4.3 (APC 4.34%, 95% CI, 4.07 to 4.62) compared to the remaining age groups.
The majority of deaths were reported at home, with 44.2% of deaths, followed by hospitals with 30.6%, hospice facilities, and long-term care centers or nursing homes with 9.9%. Men had consistently higher IHCC mortality compared to women. From 1999 to 2020, AMR rose from 1.7 to 3.6 in men (Average AAMR = 2.7, APC = 3.70%, 95% CI: 2.95 to 4.46) and from 1.4 to 2.8 in women (Average AAMR = 2.1, APC = 3.55%, 95% CI: 3.34 to 3.77).
IHCC mortality rose from 1999 to 2020 across all racial and ethnic groups. Non-Hispanic (NH) Asian and Pacific Islanders had the highest increase, while NH American Indian and Alaska Natives started highest (AAMR = 3.2 in 2001) but declined slightly (AAMR = 2.9 in 2020) with a non-significant APC of 0.48% (95% CI: –1.02 to 2.00). The NH Blacks had the lowest AAMR but the highest APC of 4.16% (95% CI: 3.78 to 4.53). African American or NH Black men consistently had higher rates compared to women (AAMR = 1.63 vs 1.25). Similar results were also observed among NH Whites (men AAMR = 1.67 vs women = 1.26).
The Northeast had the highest average AAMR at 2.6 (APC 3.70%, 95% CI: 3.46 to 3.93), followed by Midwest (APC 3.79%, 95% CI: 3.56 to 4.02) and West (APC 3.25%, 95% CI: 3.00 to 3.49) at 2.5 and the South at 2.1 (APC 3.02%, 95% CI: 2.68 to 3.38). In U.S. census divisions, New England reported the highest AAMR of 2.77 (APC 4.48%, 95% CI: 3.96 to 5.00), with New Hampshire showing the sharpest rise from 2.6 to 5.0. Metropolitan areas reported that AAMR rose from 1.5 to 3.2 (APC 3.65%, 95% CI: 3.49 to 3.80), whereas non-metropolitan areas increased from 1.4 to 2.7 (APC 3.45%, 95% CI: 3.16 to 3.74).
This study was limited by potential misclassification or omission of IHCC on death certificates. Additionally, the results may be less accurate for Native American populations and the state of Vermont due to small sample sizes and potential inconsistencies in data reporting.
In conclusion, this study reveals a consistent increase in IHCC-related mortality from 1999 to 2020 among U.S. adults aged 25 years and older. The highest AAMR rates were observed in men, older adults, metropolitan areas, the Northeast region, and NH Asian/Pacific Islanders. These findings highlight the need to improve diagnostic and treatment strategies due to IHCC’s poor prognosis.
Reference: Sohail R, Khattak R, Mumtaz R, et al. Temporal Trends and Disparities Related to Intrahepatic Cholangiocarcinoma Among Adults Living in the United States: A 1999 to 2020 Retrospective Analysis. medtigo J Med. 2025;3(2):e30623220. doi:10.63096/medtigo30623220
