DISEASE OVERVIEW IN HEPATOCELLULAR CARCINOMA (HCC)

HCC is the most prevalent type of liver cancer, which is the thirteenth most common cancer in the US and a leading cause of cancer-related deaths worldwide.^1,2

HCC is highly heterogeneous and frequently presents a dual challenge of managing the cancer itself and underlying liver dysfunction.^3,4

EPIDEMIOLOGY AND UNMET NEED

In 2025 there were 42,240 new cases of liver cancer* and 30,090 deaths in the US.⁵

HCC will have a growing impact globally over the next several decades, with the number of new liver cancer cases projected to increase from 0.87 million in 2022 to 1.52 million by 2050.⁶

PRESENTATION AND ETIOLOGY

	Early HCC	Liver-confined unresectable HCC	Advanced HCC
	Early HCC	Liver-confined unresectable HCC	Advanced HCC
Clinical presentation	Typically few, or no symptoms⁷	More prominent symptoms which may include abdominal discomfort, fatigue, and loss of appetite⁷	Severe and disease-specific symptoms, which may include gastrointestinal symptoms related to liver dysfunction and cachexia⁷
Diagnosis	30% of patients are diagnosed with very early or early HCC^8†	20% of patients are diagnosed at this stage^8†	50% of patients are diagnosed with advanced HCC (including 10% at end stage)^8†
5-year relative survival rates, 2015–2021⁹*	Localized: 37.6%	Localized: 37.6%	Regional: 13.2% Distant: 3.5%

Early HCC

Clinical presentation

Typically few, or no symptoms⁷

Diagnosis

30% of patients are diagnosed with very early or early HCC^8†

5-year relative survival rates, 2015–2021⁹*

Localized: 37.6%

Liver-confined
unresectable HCC

Clinical presentation

More prominent symptoms which may include abdominal discomfort, fatigue, and loss of appetite⁷

Diagnosis

20% of patients are diagnosed at this stage^8†

5-year relative survival rates, 2015–2021⁹*

Localized: 37.6%

Advanced HCC

Clinical presentation

Severe and disease-specific symptoms, which may include gastrointestinal symptoms related to liver dysfunction and cachexia⁷

Diagnosis

50% of patients are diagnosed with advanced HCC (including 10% at end stage)^8†

5-year relative survival rates, 2015–2021⁹*

Regional: 13.2% Distant: 3.5%

*Liver and intrahepatic bile duct cancer.^5,9

^†In Western countries (Spain, Italy, United States, Latin America).⁸

The etiology of HCC in the US is shifting; while the main risk factors have traditionally been hepatitis B and C infection, non-viral causes such as MASLD and alcohol-related liver disease are becoming more frequent.^1,10

UNMET NEED

Despite advances in understanding and treatment of HCC, significant unmet needs remain¹¹:

Diagnosis at an advanced stage is common, when curative treatments such as resection or transplantation are no longer viable¹²

Balancing preservation of liver function with reducing tumor burden through treatment can be challenging^1,13

Disparities in healthcare access, including inconsistent availability of MDT care, further complicate management^11,14

Addressing these gaps is essential for helping to improve outcomes and ensuring equitable care for all patients with HCC.¹¹

SCREENING AND SURVEILLANCE

The AASLD guidelines recommend surveillance in at-risk populations, including those with chronic hepatitis B infection or cirrhosis from any etiology.¹⁵

The guideline-recommended surveillance method is abdominal ultrasound combined with AFP testing; however, the sensitivity of this for detecting early HCC is only 63%,¹⁵ highlighting the need for advancements in surveillance techniques.

There are also implementation challenges in the US:

Low awareness of available screening guidelines and lack of a comprehensive screening program¹⁶

Low patient adherence to regular imaging, which can be influenced by factors such as scheduling and financial constraints, access to facilities, socioeconomic status, stigma, and patient perception of screening¹⁶

Lack of hepatologist involvement in high-risk patient care, leading to surveillance gaps^16,17

There is an urgent need to identify and validate reliable, non-invasive biomarkers for more effective screening, such as ctDNA, which may have the potential to detect tumor-specific genetic and epigenetic alterations in the bloodstream.¹⁸

Diagnosis and staging of HCC relies on accurate assessment of a wide range of factors.

DELVE DEEPER

Let HORIZONS HCC be your compass in navigating the complexities and latest developments in HCC patient care.

Abbreviations:

AASLD=American Association for the Study of Liver Diseases; AFP=alpha-fetoprotein; ctDNA=circulating tumor DNA; HCC=hepatocellular carcinoma; MASLD=metabolic dysfunction-associated steatotic liver disease; MDT=multidisciplinary team; US=United States.

References:

1. Llovet JM, Kelley RM, Villanueva A, et al. Nat Rev Dis Primers. 2021;7(1):6; 2. GLOBOCAN. Updated February 08, 2024. Accessed October 31, 2025. https://gco.iarc.who.int/media/globocan/factsheets/populations/840-united-states-of-america-fact-sheet.pdf; 3. Safri F, Nguyen R, Zerehpooshnesfchi S, George J, Qiao L. Cancer Gene Ther. 2024;31(8):1105–1112; 4. Pinter M, Trauner M, Peck-Radosavljevic M, Sieghart W. ESMO Open. 2016;1(2):e000042; 5. National Cancer Institute SEER Program. Accessed October 31, 2025. https://seer.cancer.gov/statfacts/html/livibd.html; 6. Chan SL, Sun HC, Xu Y, et al. Lancet. 2025;406(10504):731–778; 7. Pathomjaruwat T, Matchim Y, Armer JM. Int J Nurs Sci. 2023;11(1):66–75; 8. Kudo M. Liver Cancer. 2018;7(2):134–147; 9. National Cancer Institute SEER Program. Accessed October 31, 2025. https://seer.cancer.gov/statistics-network/explorer/application.html?
site=35&data_type=4&graph_type=5&compareBy=stage&chk_stage_104=104&chk_stage_105=105&chk_stage_106=106&series=9&sex=1&race=1&age_range=1&advopt_precision=1&advopt_show_ci=on&advopt_show_count=on&hdn_view=1&advopt_show_apc=on&advopt_display=2#resultsRegion1; 10. Rich NE. Surg Oncol Clin N Am. 2024;33(1):1–12; 11. Kronenfeld JP, Goel N. J Hepatocell Carcinoma. 2021;8:1209–1219; 12. Moris D, Martinino A, Schiltz S, et al. CA Cancer J Clin. 2025:1–15; 13. Forner A, Reig M, Bruix J. Lancet. 2018;391(10127):1301–1314; 14. Naugler WE, Alsina AE, Frenette CT, Rossaro L, Sellers MT. Clin Gastroenterol Hepatol. 2015;13(5):827–835; 15. Singal AG, Llovet JM, Yarchoan M, et al. Hepatology. 2023;78(6):1922–1965; 16. Del Poggio P, Mazzoleni M, Lazzaroni S, D'Alessio A. World J Gastroenterol. 2021;27(37):6180–6190; 17. Simmons OL, Feng Y, Parikh ND, Singal AG. Clin Gastroenterol Hepatol. 2019;17(4):766–773; 18. Schlosser S, Tümen D, Volz B, et al. Front Oncol. 2022;12:1016952.

DISEASE OVERVIEW IN HEPATOCELLULAR CARCINOMA (HCC)

EPIDEMIOLOGY AND UNMET NEED

PRESENTATION AND ETIOLOGY

UNMET NEED

SCREENING AND SURVEILLANCE

Diagnosis and staging of HCC relies on accurate assessment of a wide range of factors.

Let HORIZONS HCC be your compass in navigating the complexities and latest developments in HCC patient care.

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DISEASE OVERVIEW IN HEPATOCELLULAR CARCINOMA (HCC)

EPIDEMIOLOGY AND UNMET NEED

PRESENTATION AND ETIOLOGY

UNMET NEED

SCREENING AND SURVEILLANCE

Diagnosis and staging of HCC relies on accurate assessment of a wide range of factors.

Let HORIZONS HCC be your compass in navigating the complexities and latest developments in HCC patient care.

ABBREVIATIONS AND REFERENCES

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