Hepatitis C

The word hepatitis is derived from Greek -- "hepar" meaning liver, and "-itis" meaning inflamed or diseased. The causes of hepatitis range from chronic alcoholism to chemical toxins. In addition, at least six different viruses that cause the disease have been identified. The most prevalent chronic infection in the United States is due to hepatitis C.

Why do certain viruses target the liver? To begin with, almost all viruses target specific tissues in the body. Cold and flu viruses invade cells of the respiratory tract. Polio viruses strike nerve cells. HIV attacks key immune cells. Similarly, the natural target for the hepatitis C virus and other hepatitis viruses is liver cells, because molecules on the surface of liver cells match corresponding molecules on the surface of the viruses.

Turning liver cells into virus factories

Once inside a healthy cell, the hepatitis C virus (HCV) inserts its own genetic code into the genes of the cell, and, like an enemy invader, takes control. The virus shuts down the cell's normal functions and begins to use the cell to create new viruses. These newly formed viruses wrap themselves in pieces of the cell's outer wall before breaking free to infect other cells.

Researchers used to believe that only a small percentage of liver cells became infected with the virus. However, more recent studies show that 50 percent or more liver cells can harbor the virus. HCV is also an extremely robust virus: Scientists estimate that an infected individual can produce 10 trillion new viruses in a single day.

How does the hepatitis C virus cause disease? First, cells invaded by the virus stop functioning normally. These injured cells begin to leak an enzyme called alanine aminotransferase, or ALT. Rising levels of ALT in the bloodstream are often the first sign of liver damage. Eventually, the disruption caused by surging swarms of new viruses destroys invaded cells.

Meanwhile, the immune system struggles to fight the infection and causes inflammation in the liver, which further damages healthy liver cells. Tiny scars form as the liver tries to repair itself, in much the same way that skin heals after being injured. Unfortunately, when the infection becomes chronic, more and more scar tissue is created in a process called fibrosis. Eventually the scar tissue knits together and begins to interfere with normal liver function. Knots of this scar tissue, or nodules, form as large areas of the liver become scarred.

Slowly, more and more of the livers normal functions become impaired, causing the condition called cirrhosis. Blood no longer flows normally through the organ because the main vein that supplies blood to the liver can become restricted and even blocked. As the disease advances, the normally smooth and firm organ shrinks and becomes hard. The liver begins to fail when it becomes unable to filter toxins, drugs, or wastes from the blood, and can no longer produce the clotting factors necessary to stop bleeding. At this point, fluid builds up in the abdomen and legs and there may be bleeding in the intestines.

Hepatitis and liver cancer

In some cases, hepatitis C infection can also lead to liver cancer. In absolute numbers, new cases of liver cancer are on the rise in the United States: The incidence of liver cancer has climbed from 1.4 people in every 100,000 during the 1970s to 6.4 per 100,000 between 2001 and 2005. Today, researchers attribute the increasing number of liver cancer cases to an increasing population and note that the disease has stabilized. The American Cancer Society estimates 24,120 new cases in 2010, mostly in men.

Experts say one major reason for the increase is the surge of HCV infections that began in the 1960s. That surge came about in part when the virus entered the blood supply and began to be spread through transfusions. Another reason may be the rise in hepatitis B infections, which can also lead to liver cancer. (HIV/AIDS infection also increases the danger of liver cancer.)

Scientists are only beginning to understand exactly how hepatitis C viruses causes cancer. The invading viruses' genes disrupt the genes of healthy liver cells. Some of the genetic changes that occur interfere with normal signals that control how cells grow. Scientists suspect that the viruses' ability to stimulate cell growth may explain why infection sometimes leads to liver cancer, because cancer is a disease of runaway cell growth. Researchers have recently discovered that hepatitis C viruses can also stimulate liver cells to reproduce. This strategy creates more cells for the virus to invade, and it may also set the stage for cancer.

The future toll

Developing cirrhosis or liver cancer can take 20 to 30 years, or even longer. Medical experts predict that cirrhosis and liver cancer will take a growing toll in years to come, even though the number of new HCV infections is declining. In a 2003 analysis, scientists at Baylor University Medical Center calculated that the proportion of people infected with the virus who develop cirrhosis could increase from 16 to 32 percent by 2020. The incidence of liver cancer could climb by 81 percent, and liver-related cancer deaths could jump by 180 percent.

Although these statistics are frightening, most infections with hepatitis C do not advance to liver failure or liver cancer. What's more, new treatment options are already improving the prognosis for people with hepatitis C. It's also worth remembering that people infected with the virus can improve their odds of staying healthy by avoiding alcohol and following the appropriate drug regimen. For example, combined treatment with alpha interferon and ribavirin has been shown to arrest hepatitis C in more than half (and in some studies, nearly all) of patients treated, dramatically reducing the danger of future complications.

References

Davis, GL. et al. Projecting future complications of chronic hepatitis C in the United States, Liver Transplantation, Apr 2003, pp 331-8.

Hashem, B. et al. Dramatic rises in the incidence of hepatocellular carcinoma in the United States, abstract, Digest Disease Week Conference 2003.

Lauer, M et al. Hepatitis C virus infection, New England Journal of Medicine, July 5, 2001, pp 41-52

National Digestive Diseases Information Clearinghouse at digestive.niddk.nih.gov

American Cancer Society. How many people get liver cancer? 2010. http://www.cancer.org/Cancer/LiverCancer/OverviewGuide/liver-cancer-overview-key-statistics

American Medical Association. Cure rates becoming the norm for patients with hepatitis C. June 2007. http://www.ama-assn.org/amednews/2007/06/18/hlsc0618.htm

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