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Hepatocellular carcinoma

Definition
HCC is a disease occurring due to malignant transformation of normal hepatocytes within the liver parenchyma.
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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.
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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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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 2023), the Enhanced Recovery After Surgery Society (ERASS 2023), the Asian Pacific Association for the Study of the Liver (APASL 2023), the European Association for the Study of the Liver (EASL 2023; 2022; 2020; 2018), the American Society for Radiation Oncology (ASTRO 2022), the American Gastroenterological Association (AGA 2022), the European Federation of Societies for Ultrasound (EFSU 2020), the American Society of Clinical Oncology (ASCO 2020), and the European Society of Medical Oncology (ESMO 2018).
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Guidelines

1.Screening and diagnosis

Epidemiology: the prevalence of hapatocellular carcinoma is increasing both in Europe and worldwide; it is amongst the leading causes of cancer death globally.
A
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  • Indications for screening (liver cirrhosis)

  • Indications for screening (hemochromatosis)

  • Indications for screening (viral hepatitis)

  • Indications for screening (occupational liver disease)

  • Indications for screening (NAFLD)

  • Indications for screening (liver transplant candidates)

  • Choice of screening tests

  • Diagnostic criteria

2.Classification and risk stratification

Staging
As per AASLD 2023 guidelines:
Assess and document tumor staging, including tumor burden, degree of liver dysfunction, and ECOG performance status, at the time of initial treatment evaluation in patients with HCC.
B
Use the BCLC system for HCC staging.
B

3.Diagnostic investigations

Diagnostic imaging, computed tomography/magnetic resonance imaging, AASLD: obtain either dynamic contrast-enhanced MRI or multiphasic CT for noninvasive diagnosis of HCC.
A
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  • Diagnostic imaging (contrast-enhanced ultrasound)

  • Tumor biomarkers

  • Evaluation for portal hypertension

  • Imaging for staging (contrast-enhanced ultrasound)

  • Imaging for staging (PET)

4.Diagnostic procedures

Liver biopsy: as per AASLD 2023 guidelines, consider performing biopsy over repeat imaging in patients with an LR-4 observation if an immediate diagnosis would impact management decisions.
B
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  • Ancillary testing

5.Medical management

General principles: as per AASLD 2023 guidelines, discuss and manage cases of HCC in a multidisciplinary care setting.
B

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  • Expectant management

  • Neoadjuvant therapy

  • Adjuvant therapy

  • Primary systemic therapy (first-line therapy)

  • Primary systemic therapy (second-line therapy)

  • Management of pain

  • Palliative care

6.Nonpharmacologic interventions

Psychosocial and nutritional support: provide psycho-oncological support and counseling on adequate nutrition according to the patients' condition.
B

7.Therapeutic procedures

Local ablation
As per AASLD 2023 guidelines:
Perform local ablative therapies with curative intent in patients with solitary tumors ≤ 5 cm ineligible for or declining surgical therapy.
A
Consider performing thermal ablation (radiofrequency or microwave ablation) in patients with early-stage HCC ≤ 3 cm ineligible for or declining surgery.
B

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  • Transarterial therapies

  • External beam radiation therapy (indications)

  • External beam radiation therapy (technical considerations)

8.Perioperative care

Preoperative care, counseling
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)

9.Surgical interventions

Surgical resection, indications, AASLD: perform surgical resection in patients with localized HCC without underlying cirrhosis.
B
consider performing surgical resection in patients with cirrhosis with limited tumor burden, well-compensated cirrhosis without clinically significant portal hypertension, and an adequate future liver remnant.
B

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  • Surgical resection (technical considerations)

  • Liver transplantation (indications)

  • Liver transplantation (bridging therapy)

10.Specific circumstances

Pregnant patients: maintain ultrasound surveillance for HCC in patients with cirrhosis in accordance with screening outside of pregnancy.
B
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11.Preventative measures

Public health measures
As per AASLD 2023 guidelines:
Implement interventions such as best practice alerts or outreach programs to increase HCC surveillance adherence, given the underuse of surveillance in clinical practice.
B
Implement public health policies and interventions to address the significant mortality of HCC.
B

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  • Hepatitis B immunization

  • Management of viral hepatitis

  • Chemoprevention

  • Lifestyle modifications

  • Coffee

12.Follow-up and surveillance

Surveillance for hepatic nodules: as per AASLD 2023 guidelines, consider obtaining repeat short-interval ultrasound and AFP measurement in approximately 3-6 months in patients with a < 1 cm lesion on ultrasound.
B
consider returning to semiannual surveillance with ultrasound and AFP 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