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Hepatocellular carcinoma

What's new

The European Society of Medical Oncology (ESMO) has updated its guidelines for the diagnosis and management of hepatocellular carcinoma (HCC). Screening with abdominal ultrasound or multiphasic cross-sectional imaging (with or without alpha-fetoprotein) is recommended for patients with liver cirrhosis and viral hepatitis. Diagnosis should be based on histology and/or contrast-enhanced imaging findings, while liquid biopsy and ctDNA testing are not recommended. For early- and intermediate-stage disease, recommended treatments include surgical resection, tumor ablation, and transarterial therapies, with no adjuvant systemic therapy. For advanced disease, definitive systemic therapy is recommended, with first-line options including atezolizumab/bevacizumab, durvalumab/tremelimumab, camrelizumab/rivoceranib, nivolumab/ipilimumab, durvalumab, tislelizumab, lenvatinib, and sorafenib. Systemic chemotherapy is not recommended. External beam radiotherapy is suggested for painful bone metastases or hepatic pain. .

Background

Overview

Definition
HCC is a disease occurring due to malignant transformation of normal hepatocytes within the liver parenchyma.
1
Pathophysiology
The risk factors that induce malignant transformation of normal hepatocytes include chronic infections of HBV and/or HCV, aflatoxin toxin, cirrhosis, or consumption of large amounts of alcohol. Underlying liver cirrhosis is present in about 80-90% of patients.
2
Epidemiology
HCC accounts for 75-85% of all liver malignancies. In the US, the incidence of HCC is estimated at 7.7 cases per 100,000 person-years.
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Disease course
Clinical manifestations relate to local mass effect (abdominal pain, distension, loss of appetite, palpable masses), hepatic dysfunction (jaundice, ascites, gastrointestinal bleeding, splenomegaly, and encephalopathy), and constitutional effects of malignancy.
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Prognosis and risk of recurrence
Multiple treatment modalities exist; however, only orthotopic liver transplantation or surgical resection is curative. The overall prognosis for HCC in the US is poor with a 2-year survival < 50% and a 5-year survival of only 10%.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of hepatocellular carcinoma are prepared by our editorial team based on guidelines from the American Association for the Study of Liver Diseases (AASLD 2025,2023), the American College of Gastroenterology (ACG 2025), the European Association for the Study of the Liver (EASL 2025,2023,2022,2020,2018), the European Society of Medical Oncology (ESMO 2025), the ...
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Screening and diagnosis

Indications for screening, liver cirrhosis
As per EASL 2025 guidelines:
Obtain surveillance for HCC in patients with cirrhosis unless they have a relatively high risk of death from non-HCC causes or cannot be offered a curative-intent treatment for HCC, such as patients with Child-Pugh class C cirrhosis ineligible for liver transplantation.
B
Insufficient evidence to recomment surveillance for HCC in patients with chronic liver disease and advanced fibrosis without cirrhosis, although they have a higher risk of HCC than the general population.
I
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  • Indications for screening (hemochromatosis)

  • Indications for screening (viral hepatitis)

  • Indications for screening (occupational liver disease)

  • Indications for screening (MASLD)

  • Indications for screening (liver transplant candidates)

  • Choice of screening tests

  • Diagnostic criteria

Classification and risk stratification

Staging: as per EASL 2025 guidelines, use the BCLC staging system for tumor staging and prognostic purposes.
A
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  • Risk assessment

Diagnostic investigations

General principles
As per ESMO 2025 guidelines:
Obtain a comprehensive diagnostic work-up for HCC, including history, clinical examination, laboratory analysis, imaging, and tumor biopsy.
B
Diagnose HCC based on histological analysis and/or contrast-enhanced imaging findings.
B
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  • Tumor biomarkers

  • Diagnostic imaging (CT/MRI)

  • Diagnostic imaging (contrast-enhanced ultrasound)

  • Imaging for staging (contrast-enhanced ultrasound)

  • Imaging for staging (MRI)

  • Imaging for staging (PET)

  • Preoperative assessment

  • Genetic testing

Diagnostic procedures

Liver biopsy: as per EASL 2025 guidelines, obtain a pathological confirmation of HCC in patients without liver cirrhosis.
B
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  • Ancillary testing

Medical management

General principles: as per ESMO 2025 guidelines, offer multidisciplinary team management in patients with early- and intermediate-stage HCC.
B
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  • Management of early disease (watchful waiting)

  • Management of early disease (local ablation)

  • Management of early disease (percutaneous ethanol injection)

  • Management of early disease (radiotherapy)

  • Management of resectable disease (neoadjuvant therapy)

  • Management of resectable disease (indications for surgical resection)

  • Management of resectable disease (technical considerations for surgical resection)

  • Management of resectable disease (adjuvant therapy)

  • Management of advanced disease (general principles)

  • Management of advanced disease (first-line systemic therapy)

  • Management of advanced disease (second-line systemic therapy)

  • Management of pain

  • Palliative care (general principles)

  • Palliative care (radiotherapy)

Nonpharmacologic interventions

Psychosocial and nutritional support: as per EASL 2018 guidelines, provide psycho-oncological support and counseling on adequate nutrition according to the patients' condition.
B
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Therapeutic procedures

Transarterial therapies, transarterial embolization/chemoembolization: as per EASL 2025 guidelines, consider offering either drug-eluting bead transarterial chemoembolization or conventional transarterial chemoembolization as equivalent options in candidates for transarterial chemoembolization.
B
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  • Transarterial therapies (selective internal radiotherapy)

  • Transarterial therapies (combination with systemic therapy)

  • External beam radiation therapy (indications)

  • External beam radiation therapy (technical considerations)

Perioperative care

Preoperative care, counseling
As per ERASS 2023 guidelines:
Provide preoperative information and counseling regarding the upcoming liver surgery. Consider using brochures and multimedia support to improve verbal counseling.
B
Advise preoperative smoking cessation at least 4 weeks before hepatectomy. Advise alcohol cessation in heavy drinkers (> 24 g/day for females or > 36 g/day for males) 4-8 weeks before surgery.
A
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  • Preoperative care (nutrition)

  • Preoperative care (rehabilitation)

  • Preoperative care (biliary drainage)

  • Preoperative care (antibiotic prophylaxis)

  • Preoperative care (corticosteroids)

  • Preoperative care (preanesthetic medication)

  • Intraoperative care (anesthesia and analgesia)

  • Intraoperative care (fluid management)

  • Intraoperative care (temperature management)

  • Postoperative care (thromboprophylaxis)

  • Postoperative care (early mobilization)

  • Postoperative care (nutrition)

  • Postoperative care (antiemetics)

  • Postoperative care (laxatives)

Surgical interventions

Liver transplantation, indications: as per EASL 2025 guidelines, do not offer liver transplantation in patients without cirrhosis unresectable HCC beyond the Milan criteria, unless there is a sustained response to nonoperative therapies and a transplant benefit is assessed.
D
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Milan criteria for liver transplantation
Presence of 1 tumor ≤ 5 cm, or 2-3 tumors ≤ 3 cm
Absence of vascular invasion
Absence of extrahepatic metastases
Criteria not met
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  • Liver transplantation (bridging therapy)

  • Liver transplantation (post-transplant therapy)

Specific circumstances

Pregnant patients: as per EASL 2023 guidelines, maintain ultrasound surveillance for HCC in patients with cirrhosis in accordance with screening outside of pregnancy.
B
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Preventative measures

Lifestyle modifications: as per EASL 2025 guidelines, advise weight loss in patients with obesity, alcohol cessation, and tobacco cessation to reduce the risk of liver-related and other adverse outcomes, and to potentially lower the risk of HCC.
B
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  • Coffee consumption

  • Chemoprevention

  • Hepatitis B immunization

  • Management of viral hepatitis

  • Management of chronic liver disease

Follow-up and surveillance

Surveillance for hepatic nodules: as per AASLD 2023 guidelines, consider obtaining repeat short-interval ultrasound and α-fetoprotein measurement in approximately 3-6 months in patients with a < 1 cm lesion on ultrasound.
B
consider returning to semiannual surveillance with ultrasound and α-fetoprotein if the lesion is stable for ≥ 2 follow-up ultrasounds.
C
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  • Assessment of treatment response

  • Post-treatment follow-up

  • Management of recurrence

Quality improvement

Public health measures: as per BSG 2024 guidelines, implement national policies to prevent transmission of viral hepatitis, reduce alcohol abuse, and encourage lifestyle changes to minimize risks of obesity and metabolic syndrome.
A
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