Hepatocellular carcinoma (HCC)

What is it?

Hepatocellular carcinoma (hepatocarcinoma or HCC) is the most common primary liver tumor and in most cases is found in patients with chronic liver disease (70-90% of HCC cases) and manifests itself in a multifocal form at diagnosis (75% of cases).

The incidence of this primary liver tumor is mainly associated with the spread of hepatitis B and C viruses, which also increased in developed countries between 1950 and 1980: the geographical distribution of HCC is thus closely related to the area of distribution of such viruses. In recent years, hepatocarcinoma related to nonalcoholic steatohepatitis (NASH) is increasing and is likely to become the first case of this neoplasm in the coming years.

Many systems have been developed for determining the stages of HCC with account of both the stage of the disease and the stage of cirrhosis, as well as the clinical condition of the patient. The most commonly used classification is BCLC (Barcelona Clinic LiverCancer) and Child-Pugh score.

Causes and risk factors

Patients with cirrhosis have the highest risk of developing HCC: 90-95% of patients with HCC have underlying liver disease or cirrhosis, but there are also cases of HCC on a non-cirrhotic liver.

The most common causes of hepatopathy / cirrhosis of the liver: hepatitis B or C infection. Hepatitis B is the most common cause of HCC in the world, and hepatitis C is the most common cause of it in Europe. The risk of developing HCC in HCC carriers is 3-5% per year. Co-infection with B and C viruses further increases the risk of tumors; alcoholism; hemochromatosis; primary biliary cirrhosis; exposure to aflatoxins, a group of mycotoxins of fugal origin; matabolic syndrome and diabetes mellitus.

Which are the symptoms?

  • itching
  • bleeding from esophageal varices
  • weight loss
  • jaundice
  • confusion and hepatic encephalopathy
  • abdominal distension from ascites
  • right upper quadrant abdominal pain   

How is it diagnosed?

Histologically, the transformations that occur during carcinogenesis are usually accompanied by progressive formation of abnormal arterial vessels (tumor neoangiogenesis) and loss of the portal component. This imbalance between the components of the vascular media provides HCC with a peculiar behavior in the different contrastographic phases that imaging techniques exploit to reliably identify this neoplasm: an increase in signal in the arterial phase in the lesion compared to the surrounding parenchyma (commonly referred to as "arterial hypervascularization" or wash-in), followed by a reduction in the venous/tardinal phase, such that the lesion is moderately less contrasted than the parenchyma (an appearance defined as "early wash" or wash-out). In the presence of wash-in followed by wash-out, a nodule >10 mm appearing in a cirrhotic liver can be classified as HCC with a very high degree of confidence. All in all, newly detected nodules should be investigated with multiphasic MRI and/or CT with contrast medium, both to identify a diagnostic pattern typical of HCC ("hypervascularization" in arterial phase and wash-out in venous/tardy phase) and to perform a staging, necessary to define the prognosis and the best possible therapy, should malignancy be confirmed.

Suggested exams

How is it treated?

HCC is one of the neoplasms whose causes are better defined and therefore, at least theoretically, preventable. Moreover, epidemiological data clearly show how a population of subjects at risk is well identifiable, namely patients with liver cirrhosis and some categories of patients with chronic viral hepatitis. Thanks to the improvement in the management of liver cirrhosis complications, in particular those related to portal hypertension, HCC has recently become the first cause of death in patients with cirrhosis in a compensated phase.  
 It is indicated to perform periodic surveillance of patients with cirrhosis by biannual liver ultrasound for early identification of HCC Treatment
Curative treatments for HCC include resection, transplantation, and ablative treatments. However, many patients who cannot be treated curatively may benefit from other treatments such as chemoembolization (TACE), radioembolization (TARE), and systemic treatment with next-generation drugs (TKi), both to identify a typical diagnostic pattern of HCC ("hypervascularization" in the arterial phase and wash-out in the venous / late phase) and to perform a staging, necessary to define the prognosis and the best possible therapy, if malignancy is confirmed. (e.g., immunotherapy or molecular targeted drugs). Before proceeding to the choice of treatment for HCC, an adequate staging is always necessary. In the case of HCC on cirrhosis there is no single universally applied system, as on the contrary happens with TNM for most solid tumors. Most of these systems have only a prognostic value and, among them, there is the most used one: the BCLC algorithm (Barcelona Clinic for Liver Cancer), which also provides a first choice therapeutic indication for each stage and is the most used in the Western world. On the basis of Child-Pugh, ECOG-PS and neoplasm extension, the staging of HCC is defined according to the BCLC classification and consequently the prognosis and the optimal therapy, according to the current Western guidelines, which provide treatments differentiated by stage of disease. 
Given the complexitỳ of the clinical context in which HCC arises and the multiplicitỳ of therapeutic options, in continuous development, it should not be understood as a fixed scheme to be rigidly applied, but as a general reference point, since it is often useful to opt for a therapeutic approach tailored to the characteristics of each node, in each patient, after a collegial evaluation. 
This is particularly important for multifocal and/or large HCC, which often requires combined and/or sequential therapies.
In addition, it is often appropriate to deviate from guidelines sincè over time they have not been updated with the most recent clinical studies focusing on new therapies or new applications of standard therapies. 
Prognosis depends on the extent of hepatopathy or cirrhosis, which limit treatment options and influence the course. Liver resection, liver transplantation, and ablative treatments result in 5-year survivals of 50-70% in patients with early stages of disease. Patients with more unfavorable disease conditions (multifocal disease, lesions >5 cm, portal thrombosis, portal hypertension) are in principle not excluded from treatment with curative intent, but their course must be defined on a case-by-case basis.

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