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Risk factors for Liver Cancer - Hepatocellular Carcinoma (HCC)

Ayla is a registered Medical Doctor with area of expertise in General medicine.


On a global basis, there are more than 626,000 new cases per year of primary liver cancer, almost all being HCC and approximately 598,000 dies from HCC every year, the third most frequent cause of cancer deaths.

About 82% of HCC cases occur in developing countries with high rates of chronic HBV and HCV infections, such as in south east Asian and African countries, 52% of all HCC occurs in China.

There is a clear predominance of males with a ratio of 2.4:1.



Major Risk factors

Besides age, genetic factors, gender, chemicals, hormone and nutrition, four major etiological factors which are rising have been established:

  1. chronic viral infections (HBV, HCV)
  2. Chronic alcoholism
  3. Non-alcoholic steatohepatitis (NASH)
  4. Food contaminants (Primarily aflatoxins).

Chronic hepatitis B infection increases the risk of HCC 100-fold and is the major risk factor worldwide. Other conditions include glycogen storage disease, hereditary hemochromatosis, non-alcoholic fatty liver disease and d1 antitrypsin deficiency.

In high prevalence regions, the HBV infection begins in infancy by the vertical transmission of virus from infected mothers, which confers a 200-fold increased risk for HCC development by adulthood. Cirrhosis may be absent in as many as half of these patients, and the cancer often occurs between 20 and 40 years of age. In the western world where HBV is not prevalent, cirrhosis is present in 75% to 90% of the cases of HCC, usually in the setting of other chronic liver diseases.

Thus, cirrhosis seems to be a pre requisite contributor to the emergence of HCC in west but may have a different role in HCC that develops in pandemic areas. In China and southern Africa, where HBV is pandemic, there may also be exposure to alpha toxin, a toxin produced by fugus Aspergillus Flavus, which contaminates peanuts and grains. Alpha toxins can bind covalently with cellular DNA and cause a specific mutation in codon 249 of P-53.

Universal vaccination of children against HBV in pandemic areas can dramatically decrease the incidence of HBV infe3ction and mostly likely the incidence of HCC. Such a program started in Taiwan in 1984 has reduced HBV infection rates from 10% to less than 1% in 20 years.

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All patterns of HCC have a strong propensity for invasion of vascular structures. Extensive extrahepatic metastasis ensues, and occasionally, long snake like masses of tumor invade the portal vein (with occlusion of the portal circulation) or inferior venacava, extending even into the right side of the heart. HCC spreads extensively within the liver by obvious contiguous growth and by the development of satellite nodules. Metastasis outside the liver is primarily via vascular invasion, especially into the hepatic vein system but hematogenous metastasis especially to the lung, tend to occur late in the disease. Lymph node metastasis to the perihilar, peripancreatic and para-aortic nodes above and below the diaphragm are found in fewer than half of HCC that spread beyond the liver. If HCC with venous invasion is identified in explanted livers at the time of liver transplantation, tumor recurrence is likely to occur in the donor liver.


Clinical Features

The clinical manifestations of HCC are seldom characteristic and are masked in the western population by those related to the underlying cirrhosis or chronic hepatitis. In areas of high incidence such as tropical Africa, patients usually have no clinical history of liver disease. In both populations most patients have ill-defined upper abdominal pain, malaise, fatigue, weight loss and sometimes awareness of an abdominal mass or abdominal fullness. In many cases enlarged liver can be felt on palpation, with sufficient irregularity or nodularity to permit differentiation from cirrhosis. Jaundice, fever and gastrointestinal or esophageal variceal bleeding are inconstant findings.

Lab studies maybe helpful but are rarely conclusive. Elevated levels of serum alfa-fetoprotein are found in 50% of patients with HCC. However false positive results are encountered with yolk sac tumors and many non-neoplastic conditions, including cirrhosis, massive liver necrosis (with compensatory liver cell regeneration), chronic hepatitis, normal pregnancy, fetal distress or death and fetal neural tube defects such as anencephaly and spina bifida. Laboratory testing for alpha-fetoprotein and other proteins (serum carcinoembryonic antigen levels) often fail to detect small HCC lesions. Recently staining for glypican-3 has been used to distinguish early HCC from dysplastic nodules.

Most valuable for detection of small tumors are imaging studies. Ultrasonography, hepatic angiography, computed tomography and magnetic resonance imaging. Molecular analysis of HCC is actively being pursued will most likely lead to a new HCC classification.

The natural course of HCC involves the progressive enlargement of the primary mass until it seriously disturbs the hepatic function, or metastasizes generally first to the lungs and then to other sites.

Over all death usually occurs from 1. cachexia, 2. Gastrointestinal or esophageal variceal bleed, 3. Liver failure with hepatic coma, 4. Rupture of tumor with fatal hemorrhage.


The five-year survival of large tumors is dismal, with the majority of patients dying within the first 2 years. With implementation of screening procedures and advances in imaging, the detection of HCC less than 2cm in diameter has increased in countries where such facilities are available. These small tumors can be removed surgically with good prognostic outcome.

Radiofrequency ablation is used for local control of large tumors and chemoembolization can also be used. recent finding shows that the kinase inhibitor SORAFENIB can prolong the life of individuals with advanced stage HCC.

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2022 Ayla Asad

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