Is hepatocellular carcinoma the same as liver metastases?

No. Hepatocellular carcinoma (HCC) is a primary liver cancer, meaning that it arises from cells within the liver itself. Liver metastases originate from a cancer that started in another organ and are managed with a different treatment strategy.

Can hepatocellular carcinoma occur with a normal AFP level?

Yes. A normal AFP level does not exclude HCC, and an elevated level is not sufficient on its own to establish the diagnosis. AFP is interpreted alongside imaging and the other clinical findings and, in some patients, can provide additional information when monitoring the course of the disease.

If there is only one tumour in the liver, does surgery always have to be performed?

Not necessarily. The choice depends not only on the number of lesions, but also on tumour size and location, the function of the remaining liver, the presence of cirrhosis or portal hypertension, and the patient's general condition. Surgical resection may be appropriate for some patients, while ablation or a different treatment approach may be preferable for others.

Can immunotherapy be given if oesophageal varices are present?

The presence of varices does not by itself rule out every treatment that includes immunotherapy. It is particularly relevant, however, when a regimen containing bevacizumab is being considered, because bevacizumab can increase the risk of bleeding. Appropriate assessment and, when indicated, treatment of the varices are therefore required before therapy begins.

Is molecular testing of the tumour needed as it is in lung cancer or cholangiocarcinoma?

Not routinely at present. Unlike in some other cancers, no molecular alterations have yet become established in HCC for the routine selection of a specific approved treatment. Molecular testing may have a role in selected cases or within clinical trials.

If the cancer recurs after surgery or local treatment, does systemic therapy always have to be started?

No. Recurrence requires a new overall assessment. Depending on the number and location of the new lesions, the timing of recurrence, liver function and previous treatments, another local or interventional treatment may be possible, whereas in other cases systemic therapy is the most appropriate option.

Hepatocellular Carcinoma

Diagnosis · Staging · Liver Function · Locoregional Treatments · Systemic Treatment

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It often develops in the setting of chronic liver disease or cirrhosis, although this is not the case for every patient. Its management has an important distinguishing feature: treatment decisions depend not only on the extent of the tumour, but also on the function of the remaining liver and the patient’s general condition. Accurate staging and multidisciplinary assessment are therefore particularly important.

What Needs to Be Known Before Treatment Is Selected?

Tumour Extent

The number and size of the lesions, their location within the liver and the possible presence of disease outside the liver.

Vascular Invasion

It is particularly important to establish whether the tumour extends into major vessels, such as the portal vein or hepatic veins.

Liver Function

Hepatic reserve directly affects both prognosis and which treatments can be delivered safely.

Underlying Liver Disease

Cirrhosis, portal hypertension and other complications of chronic liver disease may substantially influence treatment selection.

The Patient’s General Condition

Performance status, comorbidities and the overall clinical picture all form part of the treatment decision.

How Is Hepatocellular Carcinoma Diagnosed and Staged?

The diagnosis of hepatocellular carcinoma has an important distinguishing feature: in patients at increased risk of HCC, a characteristic appearance on an appropriate CT or MRI scan may be sufficient to establish the diagnosis without biopsy. At the same time, both the extent of the disease and the function of the remaining liver must be assessed.

01 — Contrast-Enhanced CT or MRI

Assessment uses dynamic imaging during different phases after contrast administration. In HCC, characteristic patterns of contrast enhancement and washout are sought; in appropriate patients, these allow a non-invasive diagnosis. Findings may be reported using standardised systems such as LI-RADS.

02 — When Is Biopsy Required?

In patients with cirrhosis, chronic hepatitis B infection or a previous HCC, characteristic imaging findings may be sufficient for diagnosis. Histological confirmation is required, however, when the imaging findings are not typical or when the patient does not belong to a group in which the non-invasive criteria can be applied.

03 — The Full Extent of Disease Must Be Established

Staging assesses the number and size of lesions within the liver, possible vascular invasion and the presence of disease outside the liver. Initial staging includes contrast-enhanced imaging of the chest, abdomen and pelvis.

04 — Staging Is Not Only About the Tumour

In hepatocellular carcinoma, the extent of the disease is not sufficient on its own to determine treatment. Liver function, the presence of portal hypertension or ascites and the patient’s general condition must also be assessed. These factors influence both prognosis and treatment options.

How Is Treatment Selected?

Treatment of hepatocellular carcinoma is not determined by ‘stage’ alone. The choice is based on the extent and location of the disease, liver function, the patient’s general condition and whether a treatment with potentially curative intent can be delivered safely. Multidisciplinary assessment is therefore required.

Treatment with Potentially Curative Intent

In early-stage disease, surgical resection, liver transplantation or local tumour ablation may be considered. The appropriate option depends on both the characteristics of the tumour and the condition of the remaining liver.

Locoregional and Interventional Treatments

When the disease is mainly confined to the liver but is not suitable for surgery or ablation, intra-arterial or other locoregional treatments may be used. Their selection depends on the distribution of disease, vascular anatomy and liver function.

Systemic Treatment

When there is advanced disease, vascular invasion or extrahepatic metastases, or when locoregional treatments are unsuitable or no longer control the disease, systemic treatment takes on a central role. Current treatment options mainly include immunotherapy-based combinations and, in selected cases, targeted treatments.

The Treatment Strategy May Change Over Time

Management is not static. Response to treatment, disease progression and changes in liver function may lead to a transition from one treatment approach to another.

When Is Systemic Treatment Used?

Systemic treatment—that is, treatment that acts throughout the body and may be given intravenously, such as immunotherapy, or orally, such as certain targeted treatments—is a central part of the management of advanced hepatocellular carcinoma. Its role is not limited to patients with metastatic disease or to those who have exhausted locoregional treatment options. Depending on the extent and distribution of disease, liver function and the overall treatment aim, it may be the principal treatment or, in selected patients, form part of a broader strategy alongside locoregional or interventional procedures.

Metastatic Disease Is Not Required

Systemic treatment may also be selected when disease remains confined to the liver, if the burden or distribution of lesions, vascular invasion or other factors make an exclusively locoregional approach inadequate or unsuitable. Current guidelines emphasise that the choice between locoregional and systemic treatment should not be based on anatomical stage alone, but should be individualised within a multidisciplinary assessment.

Systemic and Locoregional Treatment Are Not Always Mutually Exclusive

In selected patients, systemic treatments may be combined with locoregional interventions such as transarterial chemoembolisation (TACE). Large randomised trials, including EMERALD-1 and LEAP-012, have shown that combining TACE with immunotherapy and anti-angiogenic strategies may prolong disease control in specific groups of patients with unresectable, non-metastatic HCC. The precise role of these strategies and the appropriate selection of patients continue to evolve.

Liver Function Remains a Determining Factor

The choice and timing of systemic treatment depend not only on the cancer, but also on the functional reserve of the liver. Preserving liver function is important both for treatment safety and for retaining access to subsequent treatment options.

The Treatment Strategy May Evolve Over Time

Hepatocellular carcinoma often requires the sequential or combined use of different treatment approaches. Response, disease progression and changes in liver function may lead to a transition from locoregional to systemic treatment, the addition of a locoregional intervention during systemic treatment, or a different treatment sequence.

How Is Systemic Treatment Selected?

Liver Function and General Condition

Most trials that established current first-line treatments mainly included patients with preserved liver function and a good general condition. Where there is significant hepatic dysfunction, the balance of benefit and risk requires particularly careful assessment.

Factors That May Influence Regimen Selection

A history of bleeding, the presence of portal hypertension or varices, cardiovascular factors, autoimmune disease and other comorbidities may influence which treatment option is most appropriate.

No Single Treatment Is Suitable for Everyone

Combinations that include PD-1 or PD-L1 inhibitors are key first-line options for eligible patients with advanced hepatocellular carcinoma, but the evidence does not allow one immunotherapy combination to be ranked simply as the best option for every patient.

What Happens After First-Line Treatment?

If the disease progresses or the initial treatment has to be discontinued, further treatment options are available. Their selection depends on what has already been given, the response to and tolerability of previous treatment, and the condition of both the liver and the patient. EASL guidance notes that tyrosine kinase inhibitors (TKIs) may be considered after ICI-based combinations in selected patients.

Frequently Asked Questions

The oral drugs used in HCC are mainly tyrosine kinase inhibitors (TKIs), such as sorafenib, lenvatinib, regorafenib and cabozantinib. They are not conventional chemotherapy. These are targeted therapies that inhibit molecular signals involved in tumour growth and the formation of new blood vessels. Today, immunotherapy-containing combinations are often key first-line options for suitable patients, while TKIs continue to have an important role when immunotherapy is not appropriate or in later lines of treatment.

Scientific Sources

The information on this page is based on international clinical guidelines and contemporary evidence for the diagnosis and management of hepatocellular carcinoma.

European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025;82(2):315–374. doi:10.1016/j.jhep.2024.08.028. Gordan JD, Kennedy EB, Abou-Alfa GK, et al. Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update. J Clin Oncol. 2024;42(15):1830–1850. doi:10.1200/JCO.23.02745. Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78(6):1922–1965. doi:10.1097/HEP.0000000000000466. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022;76(3):681–693. doi:10.1016/j.jhep.2021.11.018. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894–1905. doi:10.1056/NEJMoa1915745. Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022;1(8):EVIDoa2100070. doi:10.1056/EVIDoa2100070. Sangro B, Kudo M, Erinjeri JP, et al. Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study. Lancet. 2025;405(10474):216–232. doi:10.1016/S0140-6736(24)02551-0. Kudo M, Ren Z, Guo Y, et al. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study. Lancet. 2025;405(10474):203–215. doi:10.1016/S0140-6736(24)02575-3.

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In hepatocellular carcinoma, treatment selection depends not only on the extent of the tumour, but also on liver function and whether locoregional or systemic treatments can be delivered. In more complex cases, a comprehensive review of these factors may help inform the next treatment steps.

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