Hepatitis C: expert urges testingHepatitis is an inflammatory disease of the liver and a major, if unrecognized, health crisis in the United States. The disease has multiple forms, identified by their alphabetized viruses. The most problematic form is hepatitis C or HCV.An estimated 3.2 million Americans – mostly Baby Boomers born between the years 1945 and 1962 – are infected with HCV. Though the disease can be cured, most persons with HCV don’t even know they’re infected. Its symptoms typically do not become obvious until the disease is well-advanced. More than 15,000 Americans die from HCV each year.Recently, the U.S. Centers for Disease Control urged all Baby Boomers to be tested for HCV. The CDC estimates the one-time testing could identify more than 800,000 additional persons with the virus, and perhaps ultimately save more than 120,000 lives. We asked Alexander Kuo, MD, medical director of the Liver Transplant Program at the UC San Diego Liver Center and a leading researcher in on-going HCV clinical trials, about the CDC’s recommendation, why HCV is more problematic than other forms of hepatitis and the prospects of new treatments.      Question: Do you agree with the CDC’s recommendation that all Baby Boomers be tested for hepatitis C? Why is that particular age-demographic targeted?Answer: I do. The old recommendation was to only test people who had documented risk factors for hepatitis C such as blood transfusions before 1992, a history of intravenous drug use or tattoos. Unfortunately, healthcare providers are not very good at asking these questions of their patients, perhaps out of embarrassment or being uncomfortable with these subjects or due to a lack of time. Also, patients themselves often do not remember what they did 30 years ago so their histories can be less than reliable. Since the majority of patients infected with hepatitis C in this country were born between 1945 and 1965, it makes sense to simply screen everyone in this age group. The prevalence of infection in this group in high enough to make this strategy cost-effective.Q: Why is hepatitis C more problematic than A or B infections? A: Hepatitis A is usually a self-limited viral infection that makes people ill for 1-2 weeks, then resolves with no long-term effects. It is usually spread through contact with contaminated food, the so-called fecal-oral route of transmission. After a resolved infection, people usually develop immunity against re-exposure. There is also an effective vaccine against hepatitis A. Hepatitis B and C are different in that exposure can lead to long-term chronic infection. Chronic infection with hepatitis B or C can lead to inflammation of the liver and ultimately cirrhosis, liver cancer or death. Most people infected with chronic hepatitis B or C have no symptoms until the damage to the liver is very advanced. That’s why hepatitis C is often called the “silent epidemic.”Q: There are vaccines for A and B, but not C. Why has C so far defied vaccine efforts?A: Vaccines against hepatitis A and B are available and work by inducing the production of antibodies against these viruses by our immune system. These antibodies are protective because they bind to the virus and can prevent it from gaining a foothold in our bodies. Hepatitis C is a master at evading our immune system. It mutates rapidly and exists in our bodies as a “swarm” of closely related viruses, each with slightly different genetic make-ups. These factors make it very difficult to develop effective antibodies that can neutralize the virus. In addition, having antibodies against hepatitis C does not appear to be enough to prevent infection. Evidence suggests that you also need to stimulate a separate part of your immune system, the so-called cell-mediated immune response in order to prevent or clear the infection. Q: How is C treated? How effective are current therapies? A: One important thing to note about hepatitis C is that there is a cure. Hepatitis C exists in nature as six distinct strains, also known as genotypes. In the United States, Western Europe and Japan, genotype 1 is the most common followed by genotypes 2 and 3. Genotype 4 is most common in Egypt and the Middle East, genotype 5 is most common in southern Africa, and genotype 6 is most common in Southeast Asia, through there is significant geographic overlap.For patients with the most common strain, the genotype 1 infection, the current standard of care is to treat with a combination of three medications for 24 to 48 weeks: pegylated interferon alfa, ribavirin and a protease inhibitor (telaprevir or boceprevir are the two new drugs that were approved by the FDA in May 2011). Pegylated interferon is a subcutaneous infection that stimulates your immune system to fight against viral infections. Patients are taught to self-administer the injections once per week with a tiny needle similar to the way diabetes self-administer insulin. Ribavirin is an oral medication that has various anti-viral actions in the body that patients generally need to take twice a day. The protease inhibitors are a new class of anti-hepatitis C drugs called Direct Antiviral Agents (DAAs). These medications are small molecules that directly bind and inhibit the action of various components of the hepatitis virus machinery that it uses to make copies of itself and survive. With these new drugs between 70-75% of patients with genotype 1 infection can be cured. Patients with genotype 2 or 3 infection are currently treated with a combination of pegylated interferon alfa and ribavirin only yielding cure rates of up to 80% after 24 weeks of treatment. Q: What’s happening in terms of new research?A: We are currently in a very exciting time in hepatitis C research. There are an impressive number of new investigational agents in the drug development pipeline from multiple pharmaceutical companies. These agents are focusing on directly inhibiting the viral machinery by targeting various viral proteins necessary for survival. The most promising new agents target the hepatitis C viral protease NS3/4, the polymerase NS5B, and NS5a, which is necessary for viral assembly. The future of hepatitis C treatment is likely going to be a combination of well-tolerated, oral DAAs that no not include interferon. This will greatly increase the number of patients who would be eligible for treatment since many current patients with advanced liver disease, severe psychiatric illnesses, or autoimmune conditions are not eligible for interferon-based therapies.

Hepatitis C: expert urges testing

Hepatitis is an inflammatory disease of the liver and a major, if unrecognized, health crisis in the United States. The disease has multiple forms, identified by their alphabetized viruses. The most problematic form is hepatitis C or HCV.

An estimated 3.2 million Americans – mostly Baby Boomers born between the years 1945 and 1962 – are infected with HCV. Though the disease can be cured, most persons with HCV don’t even know they’re infected. Its symptoms typically do not become obvious until the disease is well-advanced. More than 15,000 Americans die from HCV each year.

Recently, the U.S. Centers for Disease Control urged all Baby Boomers to be tested for HCV. The CDC estimates the one-time testing could identify more than 800,000 additional persons with the virus, and perhaps ultimately save more than 120,000 lives.

We asked Alexander Kuo, MD, medical director of the Liver Transplant Program at the UC San Diego Liver Center and a leading researcher in on-going HCV clinical trials, about the CDC’s recommendation, why HCV is more problematic than other forms of hepatitis and the prospects of new treatments. 
   
Question: Do you agree with the CDC’s recommendation that all Baby Boomers be tested for hepatitis C? Why is that particular age-demographic targeted?

Answer: I do. The old recommendation was to only test people who had documented risk factors for hepatitis C such as blood transfusions before 1992, a history of intravenous drug use or tattoos. Unfortunately, healthcare providers are not very good at asking these questions of their patients, perhaps out of embarrassment or being uncomfortable with these subjects or due to a lack of time. Also, patients themselves often do not remember what they did 30 years ago so their histories can be less than reliable.

Since the majority of patients infected with hepatitis C in this country were born between 1945 and 1965, it makes sense to simply screen everyone in this age group. The prevalence of infection in this group in high enough to make this strategy cost-effective.

Q: Why is hepatitis C more problematic than A or B infections?

A: Hepatitis A is usually a self-limited viral infection that makes people ill for 1-2 weeks, then resolves with no long-term effects. It is usually spread through contact with contaminated food, the so-called fecal-oral route of transmission. After a resolved infection, people usually develop immunity against re-exposure. There is also an effective vaccine against hepatitis A.
 
Hepatitis B and C are different in that exposure can lead to long-term chronic infection. Chronic infection with hepatitis B or C can lead to inflammation of the liver and ultimately cirrhosis, liver cancer or death. Most people infected with chronic hepatitis B or C have no symptoms until the damage to the liver is very advanced. That’s why hepatitis C is often called the “silent epidemic.”

Q: There are vaccines for A and B, but not C. Why has C so far defied vaccine efforts?

A: Vaccines against hepatitis A and B are available and work by inducing the production of antibodies against these viruses by our immune system. These antibodies are protective because they bind to the virus and can prevent it from gaining a foothold in our bodies. Hepatitis C is a master at evading our immune system. It mutates rapidly and exists in our bodies as a “swarm” of closely related viruses, each with slightly different genetic make-ups. These factors make it very difficult to develop effective antibodies that can neutralize the virus. In addition, having antibodies against hepatitis C does not appear to be enough to prevent infection. Evidence suggests that you also need to stimulate a separate part of your immune system, the so-called cell-mediated immune response in order to prevent or clear the infection.

Q: How is C treated? How effective are current therapies?

A: One important thing to note about hepatitis C is that there is a cure. Hepatitis C exists in nature as six distinct strains, also known as genotypes. In the United States, Western Europe and Japan, genotype 1 is the most common followed by genotypes 2 and 3. Genotype 4 is most common in Egypt and the Middle East, genotype 5 is most common in southern Africa, and genotype 6 is most common in Southeast Asia, through there is significant geographic overlap.

For patients with the most common strain, the genotype 1 infection, the current standard of care is to treat with a combination of three medications for 24 to 48 weeks: pegylated interferon alfa, ribavirin and a protease inhibitor (telaprevir or boceprevir are the two new drugs that were approved by the FDA in May 2011). Pegylated interferon is a subcutaneous infection that stimulates your immune system to fight against viral infections. Patients are taught to self-administer the injections once per week with a tiny needle similar to the way diabetes self-administer insulin. Ribavirin is an oral medication that has various anti-viral actions in the body that patients generally need to take twice a day. The protease inhibitors are a new class of anti-hepatitis C drugs called Direct Antiviral Agents (DAAs). These medications are small molecules that directly bind and inhibit the action of various components of the hepatitis virus machinery that it uses to make copies of itself and survive. With these new drugs between 70-75% of patients with genotype 1 infection can be cured.

Patients with genotype 2 or 3 infection are currently treated with a combination of pegylated interferon alfa and ribavirin only yielding cure rates of up to 80% after 24 weeks of treatment.

Q: What’s happening in terms of new research?

A: We are currently in a very exciting time in hepatitis C research. There are an impressive number of new investigational agents in the drug development pipeline from multiple pharmaceutical companies. These agents are focusing on directly inhibiting the viral machinery by targeting various viral proteins necessary for survival. The most promising new agents target the hepatitis C viral protease NS3/4, the polymerase NS5B, and NS5a, which is necessary for viral assembly. The future of hepatitis C treatment is likely going to be a combination of well-tolerated, oral DAAs that no not include interferon. This will greatly increase the number of patients who would be eligible for treatment since many current patients with advanced liver disease, severe psychiatric illnesses, or autoimmune conditions are not eligible for interferon-based therapies.

Notes

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    Hepatitis
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    Hepatitis C: expert urges testing
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    Hmmm. Interesting.
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