Review
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World J Hepatol. Jun 27, 2013; 5(6): 311-322
Published online Jun 27, 2013. doi: 10.4254/wjh.v5.i6.311
Non-viral factors contributing to hepatocellular carcinoma
Manal A Hamed, Sanaa A Ali
Manal A Hamed, Sanaa A Ali, Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Division, National Research Centre, Dokki, Giza 12622, Egypt
Author contributions: Hamed MA and Ali SA designed the study, wrote the review and were also involved in editing the review in addition to providing financial support for this work.
Correspondence to: Sanaa A Ali, Professor of Biochemistry, Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Division, National Research Centre, El-Behooth St., Dokki, Cairo 12622, Egypt. sanaa_ahmedibrahim@yahoo.com
Telephone: +20-2-33371499 Fax: +20-2-33370931
Received: February 21, 2013
Revised: May 10, 2013
Accepted: May 18, 2013
Published online: June 27, 2013
Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide, accounting for over half a million deaths per year. The geographic pattern of HCC incidence is parallel to exposure to viral etiologic factors. Its incidence is increasing, ranging between 3% and 9% annually depending on the geographical location, and variability in the incidence rates correspond closely to the prevalence and pattern of the primary etiologic factors. Chronic infections with hepatitis B viruses or hepatitis C viruses have both been recognized as human liver carcinogens with a combined attributable fraction of at least 75% of all HCC cases. Multiple non-viral factors have been implicated in the development of HCC. Increased body mass index and diabetes with subsequent development of non-alcoholic steatohepatitis represent significant risk factors for HCC. Other non-viral causes of HCC include iron overload syndromes, alcohol use, tobacco, oral contraceptive, aflatoxin, pesticides exposure and betel quid chewing, a prevalent habit in the developing world. Wilson disease, α-1 antitrypsin deficiency, Porphyrias, autoimmune hepatitis, Schistosoma japonicum associated with positive hepatitis B surface antigen, and thorotrast-ray are also contributing hepatocellualar carcinoma. In addition, primary biliary cirrhosis, congestive liver disease and family history of liver cancer increase the risk of HCC incident. In conclusion, clarification of relevant non-viral causes of HCC will help to focus clinicians on those risk factors that are modifiable. The multilevel preventative approach will hopefully lead to a reduction in incidence of non-viral HCC, and a decrease in the patient morbidity and mortality as well as the societal economic burden associated with HCC.

Keywords: Hepatocellular carcinoma, Viral etiologic factors, Non viral factors

Core tip: Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide, there are multiple non-viral factors have been implicated in the development of HCC, hemochromatosis, obesity, diabetes, alcohol and tobacco have consistently been shown to dramatically increase the rate of HCC. Oral contraceptive, aflatoxin, pesticides exposure and betel quid chewing also increase HCC risk, in addition, Wilson disease, α-1 antitrypsin deficiency, porphyries, autoimmune hepatitis, Schistosoma japonicum infection associated with positive hepatitis B surface antigen, and thorotrast-ray are contributing in the prevalence of the disease. Moreover, primary biliary cirrhosis, congestive liver disease and family history of liver cancer play a significant role of disease progression.