Hepatocellular carcinoma

The hepatocellular carcinoma (or "liver cancer") is a malignant primary tumor of the liver. It represents the most frequent of the primary liver tumors. Its incidence, which is increasing, is 2 to 10 cases per 100,000 inhabitants per year in Western countries, with a sex ratio of 5 men to 1 woman. The vast majority of cases occur during the course of cirrhosis. Its prognosis is very severe, with a median survival of less than 3 months and a 1-year survival of about 20% from the date of diagnosis. Its management is poorly codified and based on a low level of evidence. However, some selected patients may see their survival significantly improved by aggressive management.

Etiologies

Evolution of Cirrhosis (75 to 90% of cases)

Regardless of the origin of the cirrhosis (alcoholic in 70% of cases, chronic viral hepatitis, hemochromatosis, biliary, autoimmune, Wilson's disease,…). The incidence of hepatocellular carcinoma is 1 to 5% per year on a cirrhotic liver (→ screening by ultrasound +- α-fetoprotein at least once every 6 months).

However, hepatocellular carcinoma reveals the underlying cirrhosis in about 50% of cases!

Other Causes (10 to 20% of cases)

Other liver diseases, porphyria.

De novo: on healthy liver

Exceptional.

Clinical

• General signs: asthenia, weight loss
• Hepatic signs: hard and nodular hepatomegaly, right upper quadrant pain, jaundice, signs of portal hypertension
• Signs of cirrhotic decompensation: jaundice, ascites, digestive hemorrhages, infections,…
• Neoplastic complications: degradation of general condition, fever, paraneoplastic syndromes (polycythemia, hypercalcemia, hypoglycemia,…), metastases (++ pulmonary, pleural, bone, adrenal), loco-regional invasion (hemoperitoneum, hemobilia, portal or suprahepatic thrombosis).

Diagnosis

• Clinical: the symptomatic nature generally indicates a large tumor or its dissemination.
• Abdominal ultrasound: Sensitivity of about 80% = first-line screening examination in known cirrhotics. The discovery of a hepatic nodule larger than 1 cm (or the modification of a known nodule smaller than 1 cm) necessitates a CT scan.
• The combination of an abdominal angio-CT scan and an abdominal MRI presents the best sensitivity and specificity and is essential for assessment.
• Biology:
  • α-FP: low sensitivity (50%, positive mainly for large tumors) and low specificity. However, a level above 500 mg/ml in a cirrhotic → Positive predictive value close to 100% (other tumors can, however, explain such an increase)! Its main usefulness is therefore the monitoring of cirrhotic patients.
  • Liver function and cholestasis markers variable.
  • Factor V often elevated contrasting with decreased PT (prognostic importance!)
  • Markers of paraneoplastic syndromes
• Liver biopsy: indication to be discussed by a specialized team in case of diagnostic doubt or planned intervention (risk of tumor dissemination).

Staging

To be performed if curative treatment is considered: abdominothoracic CT scan +- bone scintigraphy +- brain CT scan. Look for the presence of multiple liver lesions (MRI/CT 15 days after lipiodol injection), evaluate liver function and the severity of any underlying cirrhosis (CHILD score), and look for esophageal or gastric varices (OGD).

Therapeutic Management and Treatments

Surgery remains the fundamental therapeutic axis, the only demonstrated possibility of significantly improving survival. Radiotherapy, chemotherapy, and hormone therapy are generally ineffective. No adjuvant treatment has actually been demonstrated to be effective… but it seems logical to attempt to eradicate HCV (interferon + ribavirin) in cases of persistent C viral replication. In all cases, therapeutic decisions should be made by a specialized center if surgical intervention seems possible.

Surgery

• Transplantation = first choice for cirrhotic patients in the absence of metastasis and with a single tumor < 5 cm. To be discussed in the case of < 3 small tumors of < 3 cm. Rarely possible (performed in < 5% of patients) due to comorbidities, complications of underlying pathology, and the scarcity of grafts. When performed, the 5-year survival rate is 60 to 80%.
• Hepatectomy = first choice for non-cirrhotic patients (or cirrhotic Child A), with preserved liver function and the possibility of maintaining a sufficient residual liver volume (minimum 40%). To be discussed on a case-by-case basis in other situations where transplantation is impossible. The 5-year survival rate is 50% at 5 years.

Local Treatments

• Percutaneous destruction in several sessions: by radiofrequency or alcoholization. To be proposed in cases where resection surgery is impossible. Risk of percutaneous dissemination, monitoring, same treatment for recurrences.
• Chemoembolization = arterial injection of cisplatin or doxorubicin (or others within the framework of studies) +- arterial occlusion with synthetic particles (lipiodol) = palliative treatment.

+ Management of underlying pathology, and other associated pathologies or complications.

New Therapeutic Management - Immunotherapy

Immunotherapies (e.g., pembrolizumab, nivolumab,...) aim to stimulate the patient's immune system (lymphocyte activation, blocking control loops,...) are special forms of chemotherapy that are currently in development.

They are currently reserved in clinical routine as adjuvant treatments for initially inoperable, multi-metastatic, or recurrent cancers in order to extend life expectancy. The quality of EBM is currently low, but the results based on small series are very encouraging. It is likely that in the long term they will integrate into all treatment protocols.

Regarding hepatocellular carcinoma, their use currently remains in the realm of study protocols.