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Diagnosis
Overview

IN HEPATOCELLULAR CARCINOMA (HCC)

HCC is the most prevalent type of liver cancer, which is the thirteenth most common cancer in the United States (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

Clinical
presentation

Often few or no symptoms7

More prominent symptoms 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,
2015–2021*9

Localized: 37.6%

Localized: 37.6%

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 metabolic dysfunction–associated fatty liver disease (MAFLD) and alcohol-related liver disease are becoming more frequent.1,10

UNMET NEED

Despite advances in understanding and treatment for HCC, significant unmet needs remain:11

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

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Balancing preservation of liver function with reducing tumor burden through treatment can be challenging1,13

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Disparities in healthcare access, including inconsistent availability
of multidisciplinary team (MDT) care, further complicate management11,14

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

SCREENING AND SURVEILLANCE

The American Association for the Study of Liver Diseases (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 alpha-fetoprotein (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:

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Low awareness of available screening guidelines and lack
of a comprehensive screening program 16

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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

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Lack of hepatologist involvement in high-risk patient care, leading
to surveillance gaps16,17

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

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

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abbreviations and referencesarrow-right-purple
Abbreviations:
AASLD=American Association for the Study of Liver Diseases; AFP=alpha-fetoprotein; ctDNA= circulating tumor DNA; HCC=hepatocellular carcinoma;
MAFLD=metabolic dysfunction-associated fatty liver disease; MDT=multidisciplinary team; US=United States.
References:
1. Llovet JM, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7:6; 2. GLOBOCAN. United States of America fact sheet. https://gco.iarc.who.int/media/globocan/factsheets/populations/840-united-states-of-america-fact-sheet.pdf. Accessed September 2025; 3. Safri F, et al. Heterogeneity of hepatocellular carcinoma: from mechanisms to clinical implications. Cancer Gene Ther. 2024;31(8):1105–1112; 4. Pinter M, et al. Cancer and liver cirrhosis: implications on prognosis and management. ESMO Open. 2016;1(2):e000042; 5. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer. https://seer.cancer.gov/statfacts/html/livibd.html. Accessed September 2025; 6. Chan SL, et al. The Lancet Commission on addressing the global hepatocellular carcinoma burden: comprehensive strategies from prevention to treatment. Lancet. 2025;406(10504):731–778; 7. Pathomjaruwat T, et al. Symptoms and symptom clusters in patients with hepatocellular carcinoma and commonly used instruments: An integrated review. Int J Nurs Sci. 2023;11(1):66–75; 8. Kudo M. Management of Hepatocellular Carcinoma in Japan as a World-Leading Model. Liver Cancer. 2018;7:134–147; 9. National Cancer Institute Surveillance, Epidemiology, and End Results Program. SEER*Explorer. Liver and Intrahepatic Bile Duct SEER 5-Year Relative Survival Rates, 2015-2021. 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. Accessed September 2025; 10. Rich NE. Changing epidemiology of hepatocellular carcinoma within the U.S. and worldwide. Surg Oncol Clin N Am. 2024;33(1):1–12; 11. Kronenfeld JP and Goel N. An Analysis of Individual and Contextual-Level Disparities in Screening, Treatment, and Outcomes for Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021;8:1209–1219; 12. Moris D, et al. Advances in the treatment of hepatocellular carcinoma: An overview of the current and evolving therapeutic landscape for clinicians. CA Cancer J Clin. 2025:10.3322/caac.70018. Online ahead of print; 13. Forner A, et al. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–1314; 14. Naugler WE, et al. Building the Multidisciplinary Team for Management of Patients With Hepatocellular Carcinoma. Clin Gastroenterol Hepatol. 2015;13:827–835; 15. Amit S, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78(6):1922–1965; 16. Del Poggio, et al. Surveillance for hepatocellular carcinoma at the community level: Easier said than done. World J Gastroenterol. 2021;27(37):6180–6190; 17. Simmons OL, et al. Primary Care Provider Practice Patterns and Barriers to Hepatocellular Carcinoma Surveillance. Clin Gastroenterol Hepatol. 2019;17(4):766–773; 18. Schlosser S, et al. HCC biomarkers – state of the old and outlook to future promising biomarkers and their potential in everyday clinical practice. Front Oncol. 2022;12:1016952.