Hepatitis, in general terms, is a disease characterized by the inflammation of the liver. It can stem from a multitude of causes, including microorganisms such as bacteria, viruses, and parasites, exposure to chemical toxins such as alcohol, and side effects of otherwise innocuous medications (the most famous example being acetaminophen, better known as Tylenol, which can cause extreme liver damage in the case of an overdose). However, most of the time, when people talk about hepatitis, they are referring to one of six related viruses that attack the liver. This writeup will concentrate specifically on the hepatitis C virus (HCV).

Because the overwhelming majority of hepatitis C cases are of the chronic variety, wherein a person may be an asymptomatic carrier of the virus for years, even decades, many people misguidedly think of HCV as relatively "harmless." It is true that, in comparison with the other hepatitis viruses, HCV seems rather less severe at first glance. In and of itself, HCV is rarely a cause of death. The problem with hepatitis C is that infection with the virus drastically increases the chances of developing secondary conditions, which can indeed be fatal. HCV can open the door for a variety of other liver diseases, including cirrhosis and cancer. It is the leading cause of chronic liver disease in developed countries. Approximately 170 million people worldwide are infected.

Transmission

HCV is a flavivirus that is transmitted primarily through blood-to-blood contact. 60-70% of people infected with HCV have used illicit intravenous drugs and were infected through needle sharing. Transmission has also occurred among addicts with nasal ulcers who shared cocaine straws. HCV is prevalent among hemophiliacs and is a risk to anyone who received blood transfusions prior to July 1992. A small percentage of HCV infections occur in healthcare workers who were exposed to infected blood in the workplace.

HCV can be transmitted from an infected pregnant mother to her developing fetus. Overall, about 5-10% of babies born to infected mothers are affected, but the rate of such vertical transmission varies according to several factors. If the mother is not viremic, meaning that, although she is infected with HCV, the virus is not actively circulating throughout her bloodstream, the chances of giving birth to an infected baby drops to almost nil. On the other hand, if the mother is co-infected with both HCV and HIV, the chance of transmitting the HCV infection to her unborn baby rises to 10-15%. Also, co-infected mothers are more likely to pass on HIV to their babies than mothers who are HIV-positive but do not have hepatitis C. In almost all cases, the infected infants have the chronic form of the disease.

Although HCV can be found in extremely low levels in the breast milk of infected mothers, breastfeeding poses little to no risk of infection, according to several studies. Nevertheless, viremic mothers who have a high viral load are cautioned against breastfeeding their infants.

Other routes of transmission are still a matter of debate among the medical community. Studies on the sexual transmission of HCV have had mixed results. Generally, it appears that sexual transmission is possible, but more often than not, sexual partners remain uninfected. Until a definitive answer can be found to the question of sexual transmission, it is better to play it safe. Studies on the efficacy of latex condoms against HCV transmission are forthcoming, but for the moment they are presumed to be effective. Sexual activities that involve an increased risk for exposure to blood, such as anal sex or sex during menstruation, should be avoided if you know your partner has HCV. Finally, women should be especially aware of the risks - the overwhelming majority of HCV infections that are suspected to have been sexually transmitted occur in females.

Symptoms and Disease Progression

The incubation period for HCV is 2-12 weeks. After this period of time, infected individuals develop the acute form of the disease. In a few exceedingly rare cases, acute hepatitis C can be quite serious, even fatal. Most of the time, however, the symptoms of the acute form of the disease are either completely absent or relatively minor. Possible symptoms include fatigue, jaundice, abdominal pain, nausea, decreased appetite, muscular or joint pain, and urine that is dark in color. The acute form of the disease lasts a couple of weeks. 85% of people who go through acute hepatitis C will develop chronic hepatitis C.

Chronic hepatitis C is an insidious disease. It is not at all unusual for someone with chronic hepatitis C to remain asymptomatic for 20-30 years. Indeed, some people (up to 30%) who are infected with HCV may go their entire lives without ever developing symptoms. An equal number of HCV patients may have recurrent bouts of clinically apparent hepatitis in which they experience some or all of the symptoms above. However, for some infected individuals, HCV eventually leads to far more serious complications.

A significant percentage (roughly 20-35%) of people with chronic hepatitis C develop cirrhosis, which can, in turn, develop into fatal end-stage liver disease. In fact, cirrhosis caused by HCV is the number one reason for liver transplants in the U.S. Less common, but even more serious, is the potential for HCV to cause liver cancer. Roughly 5% of patients infected with HCV develop hepatocellular carcinoma. This particular type of cancer is often inoperable and is notorious for responding poorly to chemotherapy and other non-surgical treatments. There is no easy way to tell ahead of time if an asymptomatic HCV infection will remain relatively benign or develop into a serious liver condition. However, it is known that a person infected with HCV who also abuses alcohol is much more likely to develop cirrhosis or liver cancer.

Contrary to the common belief that hepatitis C is not fatal, the CDC reports 10,000 HCV-related deaths in the U.S. annually.

Testing and Diagnosis

The number of hepatitis C diagnoses is currently increasing. However, it is highly unlikely that this correlates to an increasing rate of infection (in fact, the rate of acute, or new, HCV infections has decreased from 230,000 per year in the U.S. in the 1980s to 25,000 annually in recent years). Although the virus has been around since at least the 1960s, accurate testing for the presence of HCV was not developed until 1989. Thus, many of the new cases are actually people who have been infected for years but had not been previously diagnosed as such.

Initial detection of HCV often occurs during routine blood tests for other medical procedures. Most often, the patient will be asymptomatic but blood tests will reveal elevated liver enzymes. In such cases, tests specific to HCV will be administered. These tests are performed on the patient's blood plasma, which is extracted from a simple blood sample.

One common test for HCV is an enzyme-linked immunosorbent assay, or ELISA, which tests for the presence of anti-HCV antibodies. In the early 1990s, the ELISA was considered a preliminary test at best, producing many false results and requiring secondary confirmation of positive results through other testing techniques. However, today, most anti-HCV ELISAs are highly accurate.

A slightly less common method of diagnosis is the HCV-RNA test, which detects the presence of the hepatitis C virus's genetic material. A technique called polymerase chain reaction (PCR) must first be used on the sample, which amplifies the number of copies of a specific region of DNA or RNA in order to produce a high enough concentration to perform testing. If used properly, the HCV-RNA test is quite accurate, but in practice, many problems arise. Because the PCR technique amplifies very small amounts of the virus's genetic material, cross-contamination of samples can easily produce false positive results. Also, the RNA tends to degrade quickly, producing false negative results depending on the age of the sample. Finally, the test is incredibly expensive, limiting its use mostly to research studies, as opposed to working medical laboratories.

After the presence of HCV has been confirmed through laboratory testing, the next stage of diagnosis is a liver biopsy, where a small amount of liver tissue is removed and examined to determine the amount of liver damage that has already occurred.

Treatment

There is no cure for hepatitis C, but there are treatments. Currently, treatments include interferon, or a combination of interferon and ribavirin. Not everyone who tests positive for HCV should be treated for the disease. If the infected person's liver enzymes are at normal levels, they are not viremic, and there is little detectable liver damage, they do not need to be treated. At the other end of the spectrum, if the patient has liver cancer or advanced cirrhosis, treatment may be too risky. Treatment is recommended for people who fall somewhere in the middle, for they are at the greatest risk of developing cirrhosis in the immediate future.

Interferon is an injectable protein that stimulates the immune system's antiviral activity, enabling the body to fight HCV itself. It comes in two varieties: standard interferon alpha, which must be self-injected three times a week, and pegylated interferon, which is long-acting and is only injected once a week. Interferon therapy usually follows a 24 or 48 week course, depending on the particular strain of HCV. The response rate is not as high as one might hope: the therapy reduces HCV-RNA levels in only 25-35% of patients.

Ribavirin is an oral antiviral medication that, by itself, does next to nothing to combat HCV. However, when ribavirin is combined with interferon, it doubles the patient response rate to therapy, reducing HCV-RNA levels in 50-60% of patients. Thus, combination therapy is currently the recommended course of treatment.

Both kinds of therapy cause uncomfortable side effects. The interferon can cause fatigue and muscle aches, migraines, nausea, skin irritation, fever, weight loss, and reversible hair loss. The addition of ribavirin tends to amplify these side effects, as well as potentially causing anemia, skin rashes, and sinusitis.

Research into new treatments for hepatitis C is hampered by the fact that HCV cannot be cultured in vitro, so all research must be conducted using test subjects.

Although HCV-related cirrhosis is the leading cause for liver transplants, liver transplantation is hardly a cure for the disease. More than 90% of transplant recipients who had HCV will develop the disease again after the transplant, and 25-30% of those will develop cirrhosis of their new liver within 5 years. More research is necessary to determine the long-term effects of transplantation, but the preliminary results are not encouraging.

Sources:
http://www.hepatitis-central.com/
http://www.hepnet.com/hepc.html
http://www.cdc.gov/ncidod/diseases/hepatitis/c/
http://www.nlm.nih.gov/medlineplus/ency/article/000284.htm
http://www-micro.msb.le.ac.uk/335/HCV.html
http://cpmcnet.columbia.edu/dept/gi/hepC.html
http://www.hepatitis-c-advocate.org/
http://www.rad.unipi.it/works/hcc/presentation-hcc.html