"Left up to my own devices, I probably would have been dead several times over."It's well known that Tyler has had drug problems and been in rehab eight times, but he has also had a slew of other health issues. He had a ligament in his knee, a broken blood vessel in his throat and, in 2005, was diagnosed with Hepatitis C. Post-surgery pain medications got him addicted to prescription pain medications, and in he took a bad tumble off a stage, lacerating his scalp, breaking his left shoulder. This, combined with his kids concerns about his health, prompted his last visit to the Betty Ford Center, which has finally kept him clean.
The hepatitis C virus (HCV) is one of the most important causes of chronic liver disease in the United States. It accounts for about 15% of acute viral hepatitis, 60% to 70% of chronic hepatitis, and up to 50% of cirrhosis, end-stage liver disease, and liver cancer. Of the U.S. population, 1.6%, or an estimated 4.1 million Americans, have antibody to HCV (anti-HCV), indicating ongoing or previous infection with the virus. Hepatitis C causes an estimated 10,000 to 12,000 deaths annually in the United States.
A distinct and major characteristic of hepatitis C is its tendency to cause chronic liver disease in which the liver injury persists for a prolonged period if not for life. About 75% of patients with acute hepatitis C ultimately develop chronic infection.
Chronic hepatitis C varies greatly in its course and outcome. At one end of the spectrum are infected persons who have no signs or symptoms of liver disease and have completely normal levels of serum enzymes, the usual blood test results that indicate liver disease. Liver biopsy usually shows some degree of injury to the liver, but the extent is usually mild, and the overall prognosis may be good. At the other end of the spectrum are patients with severe hepatitis C who have symptoms, high levels of the virus (HCV RNA) in serum, and elevated serum enzymes, and who ultimately develop cirrhosis and end-stage liver disease. In the middle of the spectrum are many patients who have few or no symptoms, mild to moderate elevations in liver enzymes, and an uncertain prognosis.
Chronic hepatitis C can cause cirrhosis, liver failure, and liver cancer. Researchers estimate that at least 20% of patients with chronic hepatitis C develop cirrhosis, a process that takes at least 10 to 20 years. Liver failure from chronic hepatitis C is one of the most common reasons for liver transplants in the United States. After 20 to 40 years, a small percentage of patients develop liver cancer. Hepatitis C is the cause of about half of cases of primary liver cancer in the developed world. Men, alcoholics, patients with cirrhosis, people over age 40, and those infected for 20 to 40 years are at higher risk of developing HCV-related liver cancer.
HCV is transmitted through parenteral exposures to contaminated blood, usually through use of injection drugs (sharing of needles or works) and to a lesser extent through exposures in health-care settings as a consequence of inadequate infection-control practices. Transmission rarely follows receipt of blood, tissues, and organs from HCV-infected donors who were not identified during routine screening activities, which have been mandated in the United States since 1992. Occupational and perinatal exposures, although less efficient, also can result in transmission of HCV. Sexual transmission of HCV had been considered to occur rarely. However, recent data indicate that sexual transmission of HCV can occur, especially among HIV-infected persons.
The most common risk factors for acquiring hepatitis C are:
- injecting drugs, including having used injection drugs only once many years ago
- having a blood transfusion before June 1992, when sensitive tests for anti-HCV were introduced for blood screening
- receiving clotting factor concentrates (such as anti-hemophilic factor) before 1987, when effective means to inactivate HCV were introduced
- hemodialysis for kidney failure
- birth to an HCV-infected mother
- suffering a needle-stick accident from a person with hepatitis C
- having sex with someone with hepatitis C or having multiple sex partners
- intranasal use of cocaine using shared equipment or paraphernalia
The therapy for chronic hepatitis C has evolved steadily since alpha interferon was first approved for use in this disease more than 15 years ago. At the present time, the optimal regimen appears to be a 24- or 48-week course of the combination of pegylated alpha interferon and ribavirin.
Alpha interferon is a host protein that is made in response to viral infections and has natural antiviral activity. Recombinant forms of alpha interferon have been produced, and several formulations (alfa-2a, alfa-2b, consensus interferon) are available as therapy for hepatitis C. These standard forms of interferon, however, are now being replaced by pegylated interferon (peginterferon).
Peginterferon is alpha interferon that has been modified chemically by the addition of a large inert molecule of polyethylene glycol. Pegylation changes the uptake, distribution, and excretion of interferon, prolonging its half-life. Peginterferon can be given once weekly and provides a more constant level of interferon in the blood, whereas standard interferon must be given several times weekly and provides intermittent and fluctuating levels. In addition, peginterferon is more active than standard interferon in inhibiting HCV and yields higher sustained response rates with similar side effects. Because of its ease of administration and better efficacy, peginterferon has replaced standard interferon both as monotherapy and as combination therapy for hepatitis C.
Ribavirin is an oral antiviral agent that has activity against a broad range of viruses. By itself, ribavirin has little effect on HCV, but adding it to interferon increases the sustained response rate by 2- to 3-fold. For these reasons, combination therapy is now recommended for hepatitis C, and interferon monotherapy is applied only when there are specific reasons not to use ribavirin.
Last week an FDA advisory panel recommended approval of two new medications, boceprevir and telaprevir, for the treatment of Hepatitis C, genotype 1. If the FDA approves these drugs (which it is expected to do), the drugs would be added to the above regimen. According to 51˶, clinical trials "showed that in the difficult-to-treat genotype 1 patients, boceprevir yielded sustained virological response rates as high as 67%", while telaprevir trials "indicated that adding the protease inhibitor could boost the sustained response rate above 70%, to as much as 90%, in patients who had never been treated for HCV."
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