Hepatocellular Carcinoma

Hepatocellular Carcinoma

Liver carcinoma or hepatocellular carcinoma (HCC) or malignant hepatoma is one of the most common malignant tumors worldwide. Each year there are between 500,000 to 1 million new cases of HCC. A rise in the incidence of mortality from HCC has been observed in different countries. The prognosis of HCC is dismal with 5-year survival being 1–4%. The global distribution of HCC is very variable.

Epidemiology

The incidence of HCC has a wide geographical variation. The incidence of HCC is more frequent in developing countries of Asia and Africa than in USA. Approximately 77% of deaths from HCC occur in developing countries. Its incidence is also steadily increasing in the West. The basis for this phenomenon emerged with the discovery of the hepatitis B virus (HBV) and the evidence that the viral infection was endemic to these same parts of the world. Hepatitis C is also a risk factor. Hepatocellular carcinoma occurs more commonly in men than in women.

Types of hepatic neoplasms

Liver cancer comprises diverse, histologically distinct primary hepatic neoplasms, which include hepatocellular carcinoma (HCC), which accounts for about 80% of all cases, and intrahepatic bile duct carcinoma (cholangiocarcinoma),which accounts for about 10 to 20% of liver cancers. Other cancers are rare. This article concentrates on hepatocellular carcinomans.

Risk factors

Major

  • Chronic hepatitis B and C viral infection
  • Chronic alcohol consumption
  • aflatoxin-B1-contaminated food
  • All agents that can cause cirrhosis in liver, such as excessive consumption of alcohol

Because there are vaccines for hepatitis B, vaccination is routine in the United States. Both hepatitis B and C are contracted via blood or other bodily fluids due to needle sharing and sometimes sexual contact. They can be passed to an infant during birth. Diagnosis of these viral infections is also important. Blood and blood products must be screened to prevent accidental transmission of these viruses.

Minor

  • Long-term oral contraceptive use in women
  • Metabolic abnormalities which lead to iron overload in liver: Hereditary haemochromatosis and porphyria cutanea tarda
  • α1-antitrypsin deficiency (appearance of antitrypsin polymers in hepatocytes)
  • Hereditary tyrosinaemia (defects in tyrosine metabolism)
  • Diabetes leading to accumulation of hepatic triglycerides which causes oxidative stress, cell death in liver
  • Non-alcoholic fatty liver disorders (NAFLD) and non-alcoholic steatohepatitis (can cause development of liver fibrosis and cirrhosis).

Symptoms of HCC

  • Abdominal mass
  • Abdominal pain
  • Emesis
  • Anemia
  • Back pain
  • Jaundice
  • Itching
  • Weight loss
  • Fever
  • Lack of appetite
  • Pain around the right shoulder blade

Diagnosis

Liver cancer may be difficult to diagnose early because patients often have no symptoms and the cancer often grows quickly.

1) Physical exam: It is difficult for the doctor to feel the liver since liver is located behind the rib cage. Big lumps can be felt only.

2) Abdominal CT scan: In this imaging technique x-rays are used. Cross-sectional pictures of the abdomen are obtained. This is done to detect masses in liver.

3) Liver scan: This test is conducted by injecting a radioactive material in the veins of a patient. The radioactive material enters the liver and then emits a type of radiation, called gamma radiation. The gamma radiation is detected by a scanner, which processes the information into a picture of the liver. Abnormalities in liver can be easily detected by analyzing these images.

4) Abdominal ultrasound: It is an imaging procedure used to examine organs of abdomen by using high-frequency sound waves.

5) Liver biopsy: A tiny piece of the affected tissue is removed for laboratory examinations. The process can be of three types: percutaneous (needle inserted through abdomen), transvenous (hollow tube inserted through the jugular vein and then in the hepatic vein), and laparoscopic (a plastic tube like instrument called cannula is inserted through a small incision in the abdomen and a needle is entered through the cannula to obtain the tissue).

6) Liver enzymes (liver function tests): These biochemical tests are conducted with blood samples of patients. Activities of ALT, AST, ALP and bilirubin in serum are high when the liver is not functioning properly. This indicates liver injury in a person, but cannot predict liver cancer.

7) Serum alpha fetoprotein: Elevated levels of serum alpha fetoprotein in blood samples of patients gives an indication of liver cancer.

Treatment

Treatment of HCC

Surgery: Surgery is the treatment of choice for HCC. But, surgery may not be always possible because of tumor extent or underlying liver dysfunction.

Liver transplantation: Transplantation is a potential therapeutic option in patients with cirrhosis and hepatocarcinoma. However, the limited number of donors restricts this application.

Percutaneous ablation and radiofrequency: This treatment is done when condition is inoperable or when liver transplantation cannot be done. Ablation is a way of destroying tumors without removing them, and can be accomplished using either chemical (alcoholization) or physical methods (radiofrequency-RFA). This technique may not be superior to surgical intervention for patients who have been diagnosed late.

Hepatic arterial chemoembolization: Hepatic arterial chemoembolization (TACE) is one of the most regular treatments for hepatocarcinoma which cannot be removed by surgery. This blocks the blood supply to the tumors.

Selective internal radiation therapy (SIRT): SIRT or intrahepatic radiotherapy is based on the local intra-arterial administration of a radionuclide, Yttrium 90. The procedure can be carried out under local anesthesia. The radioisotope directly enters into the hepatic artery and then its radiation can destroy the tumor tissue sparing the rest of the organ.

Chemotherapy, immunological and hormonal treatments: Chemotherapy with cytotoxic agents such as doxorubicin, cisplatin or 5-fluorouracil showed a low response rate (<10%) without a clear benefit in overall survival. Chemotherapy can be directed to the tumors by putting it into the hepatic artery.

Targeted therapy: Treatment of advanced HCC can be done by targeted therapies which consist largely of tyrosine kinase inhibitors and monoclonal antibodies. In May 2009, sorafenib (Nexavar®) was approved in Japan for unresectable hepatocellular carcinoma (HCC). Sunitinib malate and sorafenib are multikinase oral inhibitors which show promise in clinical trials. Bevacizumab, which is a recombinant humanized monoclonal antibody against VEGF, can be used in combination with other chemotherapeutic drugs to treat patients of HCC. Tyrosine kinase inhibitor drugs against EGFR 1 and 2 like erlotinib, gefitinib and lapatinib are in clinical trials.

Prognosis

Only 10 – 20% of hepatocellular carcinomas can be removed completely using surgery. Partial removal of the cancerous tissue does not protect the patient. The disease can cause death within 3 to 6 months. Therefore, we can say that prognosis for HCC is poor. Late presentation with large tumors and lack of medical expertise and facilities in this field is a major cause of poor prognosis. Liver carcinoma is fatal even in developed countries. Recent improvement in treatment of HCC may improve survival rates.

References

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  10. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.