Therapeutic targets
- Liver transplantation (LTx)
- Palliative (palliative treatment)
Therapy recommendations
- First-line therapy is total hepatectomy (complete removal of the liver) and orthotopic liver transplantation for simultaneous therapy of hepatocellular carcinoma and underlying disease. Indications: According to the guidelines (DGVS, EASL, AASLD) based on the Milan criteria (Milan criteria): radiological evaluation (foci ≤ 5 cm or max. 3 foci each ≤3 cm, no vascular involvement, no extrahepatic manifestation).
- In the presence of extrahepatic (“outside the liver”) manifestations or elevated bilirubin levels, therapy may be with:
- Selective internal radiotherapy (SIRT, TACE) – irradiation of the tumor from within (see below radiotherapy).
- Drug therapy with sorafenib – active substance from the group of multi-kinase inhibitors. Used in advanced hepatocellular carcinoma (unresectable hepatocellular carcinoma, HCC) when standard therapy has failed or is unsuitable). This therapy can halt tumor growth for a period of time, relieve tumor-related symptoms, but cannot cure hepatocellular carcinoma.
- First-line therapy:
- Sorafenib (protein kinase inhibitor from the multi-kinase inhibitor group) (OS: 10.7 mo; TTP: 5.5 mo).
- Lenvatinib (tyrosine kinase inhibitor (TKI)) (OS: 13.6 mo; TTP: 8.9 mo).
- Second-line therapy
- Regorafenib (kinase inhibitor) for second-line treatment of hepatocellular carcinoma (HCC); OS: 10.6 mo; TTP: 3.2 mo.
- Cabozantinib (multikinase inhibitor) extended progression-free survival from a median of 1.9 to 5.2 months and overall survival from 8.0 to 10.2 months in patients with hepatocellular carcinoma (HCC) who had developed resistance to sorafenib in a phase 3 trial. (Approval has since been granted: Monotherapy for the treatment of hepatocellular carcinoma (HCC) in adults previously treated with sorafenib).
- Ramucirumab (monoclonal antibody (IgG1) targeting vascular endothelial growth factor receptor 2 (VEGFR2)) (OS: 8, 5 mo; TTP: 3.02 mo).
- Pembrolizumab immune checkpoint inhibitors: PD-1 inhibitor) (OS: 13.9 mo; PFS: 3.0 mo).
- Drug therapy with sorafenib can also be used in combination with the local ablative procedures (e.g., radiofrequency ablation, transarterial chemoembolization).
- Supportive therapy:
- Ascites (abdominal dropsy): diuretics.
- Therapy of classic complications such as cholestasis, cholangitis, thrombosis.
- Pruritus in patients with hepatogenic jaundice:
- Cholestyramine (cholesterol resorption inhibitor): 4-16 g/day (4 h separated from intake of other drugs).
- Rifampicin (bactericidal antibiotic from the ansamycin group): 150-600 mg/day; caveat: hepatotoxicity (after 4-12 weeks).
- Opioid antagonists: naloxone (0.2 μg/kgKG/min), naltrexone (25-50 mg/day).
- Sertraline (antidepressant from the selective serotonin reuptake inhibitor group): 75-100 mg/day.
- Pain therapy for bone metastases
- In advanced stages, palliative therapy (palliative treatment) is given:
- Enteral nutrition, e.g., feeding via a PEG (percutaneous endoscopic gastrostomy: endoscopically created artificial access from the outside through the abdominal wall into the stomach).
- Infusion therapy via a port catheter (port; permanent access to venous or arterial blood circulation).
- Pain therapy (according to WHO staging scheme; see “Chronic pain” below).
- See also under “Further therapy”.
Legend: OS = overall survival; PFS = progression-free survival; TTP = time to progression; ORR = objective response rate.
Further notes
- Patients with unresectable hepatocellular carcinoma:
- Atezolizumab (IgG1κ monoclonal antibody against PD-L1) in combination with bevacizumab (monoclonal antibody that binds to vascular endothelial growth factor (VEGF), thereby inhibiting its interaction with its receptors) as first-line treatment reduced the risk of death by 42% and reduced the risk of worsening disease progression by 41% compared with standard therapy with sorafenib. Atezolizumab, in combination with bevacizumab, has received EU approval in adult patients with advanced or unresectable hepatocellular carcinoma (HCC). It is thus the first approved cancer immunotherapy in hepatocellular carcinoma.
