Hepatocarcinoma

Hepatocarcinoma is the most common type of liver cancer and is estimated to account for between 80% and 90% of all hepatic tumors. It originates in hepatocytes, the predominant liver cells that are organized into the hepatic parenchyma, which is responsible for functions such as protein synthesis and bile production, among others.

It is rare for hepatocarcinoma to develop in a healthy liver, as it is usually associated with a pre-existing condition such as hepatitis, cirrhosis, or non-alcoholic fatty liver disease.

Hepatocarcinoma can be divided into three types according to its growth pattern:

• Solitary nodular or massive hepatocarcinoma: the most common form. A single, well-defined tumor develops and may be encapsulated.
• Multinodular or multifocal hepatocarcinoma: consists of multiple tumors distributed across different segments of the liver. It is most common in patients with advanced cirrhosis.
• Infiltrative or diffuse hepatocarcinoma: cancer cells do not form a discrete tumor but instead spread throughout the liver, replacing healthy hepatic tissue. Due to its characteristics, it is very difficult to diagnose, as it may be confused with cirrhosis.

The prognosis of hepatocarcinoma depends on the stage at diagnosis. It generally has a poor outcome, as it is a highly aggressive tumor and is currently the second most lethal cancer after pancreatic cancer. Life expectancy for untreated patients with hepatocarcinoma ranges from three years to four months. With appropriate treatment, the 5-year survival rate is achieved in early stages, while in advanced stages survival is approximately 11 months.

According to the Spanish Association Against Cancer, hepatocarcinoma staging is as follows:

• Early stage (A): patients are asymptomatic and have preserved liver function. They present with a single tumor or up to three tumors smaller than 3 cm. They are candidates for curative treatments, with a 5-year survival rate of 50–75%.
• Intermediate stage (B): patients remain asymptomatic and have a large or multinodular tumor. Life expectancy increases with treatment, and 3-year survival is estimated at 50%.
• Advanced stage (C): patients present with symptoms, and tumors have invaded blood vessels or spread to other organs. Treatments are palliative, with a 6-month survival rate of 50%.
• Terminal stage (D): patients have large, symptomatic, or disseminated tumors. Palliative care is provided to improve quality of life. The 3-month survival rate is 50%.

Symptoms

Hepatocarcinoma rarely causes symptoms in its early stages. When symptoms do occur, they may include:

• Gallbladder obstruction
• Jaundice: yellow discoloration of the skin, mucous membranes, and sclera
• Hemorrhage if neoplasms rupture

In advanced stages, symptoms commonly include:

• Severe fatigue
• Loss of appetite
• Unexplained weight loss
• Abdominal pain
• Pruritus
• Palpable mass in the upper right abdomen
• Sudden worsening of cirrhosis in affected patients
• Fever
• Abdominal distension

Causes

As previously mentioned, hepatocarcinoma usually occurs in patients with long-standing chronic liver disease:

• Chronic hepatitis: infection caused by hepatitis B or C virus
• Cirrhosis: formation of scar tissue in the liver due to excessive alcohol consumption, metabolic disorders, or viral hepatitis infection
• Metabolic liver disease: metabolic dysfunction–associated fatty liver disease, characterized by excessive fat accumulation in the liver due to conditions such as:
• Obesity
• Insulin resistance
• Type 2 diabetes
• Dyslipidemia: elevated blood lipid levels (cholesterol, triglycerides)
• Alcoholism: chronic excessive alcohol consumption increases the risk of cirrhosis and, consequently, hepatocellular carcinoma
• Hereditary liver diseases:
• Hemochromatosis: accumulation of iron in the body, particularly in the liver
• Alpha-1 antitrypsin deficiency: decreased blood levels of AAT due to hepatic accumulation, promoting destruction of healthy liver cells
• Tyrosinemia: impaired tyrosine metabolism leading to tissue accumulation and potential liver failure or renal dysfunction
• Von Gierke disease: metabolic disorder that prevents proper glycogen type Ia metabolism, leading to glycogen and fat accumulation in the liver and kidneys
• Wilson disease: genetic disorder causing copper accumulation in the liver, brain, and other organs

Risk Factors

Risk factors for hepatocarcinoma include:

• Age: typically diagnosed after 40 years of age
• Geographic location: liver cancer is more prevalent in Southeast Asia and Africa, where hepatocarcinoma often develops without pre-existing liver disease
• Cirrhosis
• Hepatitis B or C infection
• Alcoholism
• Obesity, which increases the risk of non-alcoholic fatty liver disease
• Diabetes, also a risk factor for fatty liver disease

Complications

The most significant complications of hepatocarcinoma include:

• Metastasis: spread of liver cancer to other organs, particularly lymph nodes, bones, or lungs
• Portal vein thrombosis: tumor invasion of the vein carrying blood from the intestines, stomach, pancreas, spleen, and gallbladder to the liver, leading to obstruction of blood flow

Other complications are usually related to the underlying liver disease:

• Liver failure
• Ascites: accumulation of fluid in the abdomen
• Gastrointestinal bleeding
• Malnutrition
• Hepatic encephalopathy: confusion or reduced brain function due to accumulation of toxins not cleared by the liver

Prevention

Preventive strategies focus on avoiding cirrhosis and hepatitis. Recommendations include:

• Immunization: vaccination against hepatitis B and C viruses. In Spain, the recommended schedule includes three doses (at 2, 4, and 11 months of age) if the mother is immunized; otherwise, an additional dose is administered within the first 24 hours of life
• Avoiding alcohol or consuming it in moderation
• Adhering to specialist-prescribed treatments for hepatitis, cirrhosis, fatty liver disease, or hemochromatosis
• Maintaining a healthy weight
• Regular physical activity
• Proper diabetes control
• Balanced diet

Which specialist treats hepatocarcinoma?

Hepatocarcinoma is managed by medical oncology and radiation oncology specialists. Gastroenterology play a key role in diagnosis.