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Primary liver cancer deaths increasing
By Timothy Tankosic, M.D.
While deaths from cancer of all causes decreased 1.1% per year between 1993 and 2002, death rates from primary liver cancer (hepatocellular carcinoma) increased by annual rates of 3% among white men, 4.5% among black men, 3.7% among white women, and 5% among Hispanic women. Although primary liver cancer is relatively rare in the U.S.--it is the 20th most common type of cancer--it ranks 8th among leading causes of cancer death because diagnosis most often occurs only after the emergence of symptoms of advanced disease. Primary liver cancer is much more common in some regions outside the U.S, particularly Southeast Asia and sub-Saharan Africa. In Japan, incidence has increased markedly during the last 25 years; liver cancer is now the third leading cause of cancer deaths among men and the fifth among women.
Hepatitis C virus (HCV) causes at least 50% of liver cancer cases in the U.S. and 60% of cases in industrialized countries worldwide. [Worldwide, the combination of HCV and HBV accounts for 75% of all cases of liver disease.] The large number of people infected with HCV, HBV, or both in the U.S. is expected to drive increases in liver cancer cases during the next 10-20 years. The incidence of HCV and HBV each have dropped dramatically--from about 240,000 per year during the 1980s for HCV to about 25,000 this year and from about 21,000 per year in 1990 to fewer than 8,000 this year for HBV. The prevalence of each disease is high, however, and large numbers of infected patients are at risk for developing liver cancer decades after the initial infection. Risk factors for HCV include drug use with contaminated needles, unprotected sex with HCV carriers, and tattooing and body piercing. Nearly all transfusion-caused cases occurred before an antibody test specific for HCV became available and routine screening of donor blood was instituted in 1992. Many people with HCV are unaware of their infection because the virus may not cause symptoms for 10 or 20 years--the result of a blood test for insurance purposes is not an uncommon way for an individual to learn of his or her HCV infection. Risk factors for HBV include blood and blood product exposure, sexual transmission, and mother to infant transmission in the perinatal period, which is a major route where HBV is endemic. [See Table 1]
HCV and HBV cause liver cancer by different mechanisms. HCV disrupts normal P53 tumor suppressor gene activity; HBV subverts cellular functions by integrating into normal liver cell DNA. Cirrhosis (scarring of the liver) then occurs, and mutations leading to malignant growth may occur as the liver (a regenerative organ) attempts self-repair. An estimated 5% of people with cirrhosis, regardless of the etiology, go on to develop liver cancer. Chronic alcohol abuse is another major cause of primary liver cancer. In developed countries, alcohol-induced cirrhosis combined with chronic HCV is the leading cause of liver cancer. Other risk factors include exposure to particular industrial chemicals (e.g., vinyl chloride, benzene) and the fungal toxin aflatoxin B (common on crops in Sub-Saharan Africa and China), hemochromatosis (excessive iron accumulation causing liver cancer in up to 30% of its victims), possibly anabolic steroids and estrogen, and less significant and understood factors such as BRCA1 and 2 gene mutations, diabetes, and smoking.
Suspicious liver lesions are always biopsied. In non-cirrhotic patients, small tumors confined to a single lobe and well located for surgical removal (i.e., with regard to blood vessels and bile ducts), may be resected with the possibility of cure.
Liver transplantation is a very effective option for early liver cancer, particularly when the tumor has not yet metastasized. This option is limited, however, by the shortage of donor organs and the current limits of acceptability of living donor procedures. During 2004, approximately 17,000 people were on the waiting list for donor livers; 6,167 liver transplants were performed. Most liver cancer is advanced, however, and chemotherapy, radiofrequency ablation, and other treatments are usually employed.
Better screening might slow the trend of increasing mortality from primary liver cancer. Because it is a fast-growing tumor rarely diagnosed in the early stages, liver cancer is typically fatal within a year of diagnosis. Unfortunately, no completely accurate, cost effective screening test is available. A blood test for ?-fetoprotein (AFP) is sometimes used, but increased AFP levels are also associated with other, non-cancerous liver diseases. Better screening, diagnosis, and treatment of HCV are critically needed to reduce the number of diseased livers that progress to cancerous livers.
In the meantime, failures to the first-line treatment for chronic HCV--pegylated interferon ?-2 plus ribavirin--are contributing to the waiting list for liver transplantation. First-line therapy is effective in about half of all treated patients. Approximately 200,000 non-responders have been identified in the U.S., and this group is increasing by an estimated 50,000 per year. In industrialized countries worldwide, HCV accounts for 70% of cases of chronic hepatitis, 40% of cases of end-stage cirrhosis, and 30%-40% of liver transplants.
Table 1 - Liver Cancer Epidemiology (2005)
| Parameter | Comments |
| Primary Liver Cancer—U.S. | |
| Estimated incidence | 17, 600 |
| Estimated prevalence | 21, 000 |
| Estimated deaths | 15, 400 |
| Incidence as a fraction of all new cancer areas | About 2% |
| Annual increase in U.S. death rate (1993-2002) | |
| White males | 3% |
| Black males | 4.5% |
| White females | 3.7% |
| Hispanic females | 5.0% |
| Cancer of all causes | -1.1% |
| Primary Liver Cancer—Worldwide | |
| Estimated new cases | 630, 000 |
| Estimated prevalence | 800, 000 |
| Secondary Liver Cancer—Worldwide | |
| Estimated incidence | 515, 000 |
| Estimated prevalence | 910, 000 |
| Chronic HCV – US | |
| Estimated prevalence (infection or prior exposure) | 3.9 million |
| Estimated incidence | 25, 000 |
| Chronic HBV –US | |
| Estimated prevalence | 1.2 million |
| Estimated incidence |
To make any comments on this article, or to ask a question of the author, please contact the publisher. If you would like to submit an article, please contact the editors. The opinions expressed in the articles published in this section do not necessarily reflect those of Pharmalicensing or UTEK Corporation. No actions including proposals to or agreements with other companies should be taken by any reader without obtaining specific business or legal advice. Neither the publisher nor the authors accept any liability for any actions or activities undertaken by any reader or other third party as a consequence of these articles or for any errors or omissions therein. Related articlesLatest articlesMost viewed articlesArticle categories   © Copyright 1995-2009 Pharmalicensing Ltd, is a division of |
