Hepatocellular carcinoma (malignant hepatoma)  

Overview

Human liver disease, cirrhosis, chronic inflammation. The concept of cancer treatment, hepatitis.Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver derived from the parenchymal cells. HCC is one of the most frequent cancer types worldwide. Usually (up to 80% of cases) this tumor occurs in individuals who have preceding chronic liver disease and cirrhosis. Chronic hepatitis B is considered a major risk factor for HCC. The disease may be asymptomatic for a long time and often is detected accidentally during the screening examination. Therefore, individuals with chronic liver diseases should be screened for HCC.

Incidence

HCC is the sixth most common type of cancer worldwide and the third leading cause of cancer-related death.  The annual global incidence of HCC is about 1 million cases with a higher prevalence in males (male-to-female ratio is 4:1). The disease incidence is significantly higher in regions with a high prevalence of viral hepatitis B and C such as Africa and Asia.

Causes

The exact cause of HCC remains unclear. It is considered that chronic inflammation of the liver, induced by alcohol consumption, hepatitis viruses, autoimmune disorders or other toxic substances.

Risk factors

Various disorders are associated with the increased risk of developing hepatocellular carcinoma including:

  • Cirrhosis of any cause;
  • Chronic hepatitis B (especially with high level of virus replication and hepatitis D coinfection) and C;
  • Chronic alcohol consumption;
  • Aflatoxin B1 and other mycotoxins;
  • Nonalcoholic fatty liver disease (NAFLD), or nonalcoholic steatohepatitis (NASH);
  • Primary biliary cirrhosis;
  • Hemochromatosis;
  • α1-antitrypsin deficiency;
  • Glycogen storage diseases;
  • Wilson’s disease;
  • Hereditary tyrosinemia;
  • Radiation exposure;

Male gender, age over 55 years, Asian and Hispanic ethnicity, family history of HCC in a first-degree relative, overweight and obesity (especially in early adulthood), tobacco use, diabetes mellitus,  hypothyroidism  (in women) are also associated with the increased risk of developing hepatocellular carcinoma. Some studies suggest that long-term use of oral contraceptives may also increase.

On the other hand, consumption of coffee, vegetables, white meat, fish, and omega-3 polyunsaturated fatty acids; aspirin use;  and statin and metformin therapy in individuals with diabetes are considered protective. 

Symptoms

Early in the course of the disease, there are no symptoms. Sometimes it is discovered during a screening examination in individuals with chronic liver diseases. When a tumor starts to grow the liver function typically is impaired. On the other hand, disease manifestation may vary depending on the underlying cause of the carcinoma.  

  • Dull abdominal pain and/or fullness and swelling in the right upper-quadrant, sometimes pain is referred to shoulder;
  • Unintended weight loss;
  • Weakness;
  • Anorexia;
  • Jaundice;
  • Fever;
  • Nausea;

During the examination, the liver usually appears enlarged.

Carcinoma typically has lymph node metastases, while lung and bone metastases occur rarely.

Diagnosis

  • Blood tests and liver function tests: Alpha-fetoprotein is considered a serum marker for HCC, although normal AFP values do not exclude HCC. Serologic tests to identify hepatitis A,  B and  C should be performed.
  • Ultrasound: Ultrasound examination is commonly used as a screening tool. The tumor is characterized by the increased vascularity and significantly higher blood supply of the mass in comparison to the other tissues.
  • CT/MRI: CT scan of the abdomen and pelvis should be performed to detect the lesion and estimate its size and spread.
  • Biopsy: The tumor appears as a large solitary tumor or a multicentric tumor with a bigger central lesion and multiple satellite neoplasms. The tumors look like yellowish-white nodules with areas of hemorrhages and dead tissues.

Treatment

Surgery is the best option for the treatment in case of HCC.

Resection of the tumor may be curative only if liver function is not impaired and there are no signs of portal vein thrombosis. In the case of cirrhosis (especially at advanced stages of the disease) the resection of the lesion is not possible, therefore, liver transplantation should be performed. Liver transplantation is also preferred to resection in case of hepatitis C as an underlying cause of HCC.

At the early stages of the disease, the lesion may be destroyed by the chemical substances (percutaneous ethanol injections) or by extremely low (cryoablation) or high (radiofrequency ablation) temperatures, which are delivered through the skin, during the laparoscopy or open surgery.

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