What are the EASL treatment guidelines for hepatocellular carcinoma?

Answer

Vaccination against hepatitis B reduces the risk of HCC and is recommended for all newborns and high-risk groups.

In patients with chronic hepatitis, antiviral therapies leading to maintained hepatitis B virus (HBV) suppression in chronic hepatitis B and sustained viral response in hepatitis C are recommended, since they have been shown to prevent progression to cirrhosis and HCC development.

Once cirrhosis is established, antiviral therapy is beneficial in preventing cirrhosis progression and decompensation. Furthermore, successful antiviral therapy reduces but does not eliminate the risk of HCC development. Antiviral therapies should follow the EASL guidelines for management of chronic hepatitis B and C infection.

Coffee consumption has been shown to decrease the risk of HCC in patients with chronic liver disease. In these patients, coffee consumption should be encouraged.

Diagnosis of HCC in cirrhotic patients should be based on non-invasive criteria and/or pathology.

In noncirrhotic patients, diagnosis of HCC should be confirmed by pathology.

Noninvasive criteria can only be applied to cirrhotic patients for nodule(s) ≥1 cm, in light of the high pre-test probability and are based on imaging techniques obtained by multiphasic computed tomography (CT), dynamic contrast-enhanced magnetic resonance imaging (MRI), or contrast-enhanced ultrasound (CEUS). Diagnosis is based on the identification of the typical hallmarks of HCC, which differ according to imaging techniques or contrast agents (arterial phase hyperenhancement (APHE) with washout in the portal venous or delayed phases on CT and MRI using extracellular contrast agents or gadobenate dimeglumine, APHE with washout in the portal venous phase on MRI using gadoxetic acid, APHE with late-onset (>60 s) washout of mild intensity on CEUS).

Because of their higher sensitivity and the analysis of the whole liver, CT scanning or MRI should be used first.

Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan is not recommended for early diagnosis of HCC because of the high rate of false-negative cases.

In patients at high risk of developing HCC, nodule(s) less than 1 cm in diameter detected by ultrasound should be followed at ≤4-month intervals in the first year. If there is no increase in the size or number of nodules, surveillance could be returned to the usual 6-month interval thereafter.

In cirrhotic patients, diagnosis of HCC for nodules of ≥1 cm in diameter can be achieved with non-invasive criteria and/or biopsy-proven pathologic confirmation.

Repeated bioptic sampling is recommended in cases of inconclusive histologic or discordant findings, or in cases of growth or change in enhancement pattern identified during follow-up, but with imaging still not diagnostic for HCC.

Staging systems for clinical decision making in HCC should include tumor burden, liver function, and performance status.

Multiphasic contrast-enhanced CT scanning or MRI is recommended for assessment of response after resection, loco-regional, or systemic therapies.

Perioperative mortality of liver resection (LR) in cirrhotic patients should be less than 3%.

LR is recommended for single HCC of any size and in particular for tumors >2 cm, when hepatic function is preserved, and when sufficient remnant liver volume is maintained.

Tumor vascular invasion and extrahepatic metastases are an absolute contraindication for liver transplantation in HCC.

Thermal ablation with radiofrequency is the standard of care for patients with BCLC (Barcelona Clinic Liver Cancer) 0 and A tumors not suitable for surgery. Thermal ablation in single tumors 2 to 3 cm in size is an alternative to surgical resection based on technical factors (location of the tumor) and hepatic and extrahepatic patient conditions.

In patients with very early stage HCC (BCLC-0), radiofrequency ablation in favorable locations can be adopted as first-line therapy even in surgical patients.

Ethanol injection is an option in some cases where thermal ablation is not technically feasible, especially in tumors < 2 cm.

Sorafenib is the standard first-line systemic therapy for HCC. It is indicated for patients with well-preserved liver function (Child-Pugh A) and with advanced tumors (BCLC–C) or earlier stage tumors progressing upon or unsuitable for loco-regional therapies.

Lenvatinib has been shown to be non-inferior to sorafenib and is also recommended in first-line therapy for HCC given its approval. It is indicated for patients with well-preserved liver function (Child-Pugh A class), with good performance status, and with advanced tumors – BCLC-C without main portal vein invasion or tumors progressing upon or unsuitable for loco-regional therapies.

Regorafenib is recommended as second-line treatment for patients tolerating and progressing on sorafenib and with well-preserved liver function (Child-Pugh A class) and good performance status. Recently, cabozantinib has shown survival benefits versus placebo in this setting.

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