Dr. David Bernstein is chief of the Division of Hepatology / Center for Liver Disease at the North Shore-LIJ Health System, and a professor of medicine at Hofstra North Shore-LIJ School of Medicine. He contributed this article to LiveScience's Expert Voices: Op-Ed & Insights.
Hepatitis C has been called a silent epidemic: As the most common blood-borne viral infection in the country, it affects more than 7 million Americans — yet, most don't know they have it. But the condition can lead to the development of cirrhosis and liver cancer, and is the leading indication for liver transplantation in the United States.
Baby boomers have the highest rate of hepatitis C infection, so the Centers for Disease Control and Prevention (CDC) recently recommended that all people born between 1945 and 1965 get tested at least once for it. People with other risk factors for hepatitis C (e.g., previous intravenous drug users, previous cocaine users, recipients of blood transfusions before 1992, and people with tattoos and body piercings in places other than the ears) should also get tested, regardless of age.
Once hepatitis C is diagnosed, it is curable, unlike other common blood-borne viruses , such as hepatitis B and HIV. Advances in hepatitis C therapies have been rapid. The first therapy for hepatitis C infection consisted of interferon injections alone, with a cure rate of less than 10 percent. In the mid-1990s, a pill called ribavirin was added to injectable interferon, and cure rates increased to about 40 percent. For more than 10 years, once-weekly injectable interferon plus oral ribavirin for a course of 24 to 48 weeks was the standard treatment method.
The high prevalence of hepatitis C has led to a considerable effort to improve cure rates with newer therapies. The first step was to understand the mechanism of hepatitis C viral replication. After researchers determined the disease's molecular structure, they identified the two main classes of enzymes involved in hepatitis C replication: protease and polymerase inhibitors. As a result of that research, direct-acting medications were manufactured to inhibit those enzymes — thus preventing replication and promoting higher cure rates.
In May 2011, the U.S. Food and Drug Administration approved the first new hepatitis C therapies in a decade. Two new oral agents — boceprevir and telaprevir, from the class of drugs called protease inhibitors — were approved for use in combination with pegylated interferon and ribavirin. These new, triple-therapy regimens have seen cure rates as high as 70 to 75 percent. Therapy lasts from 24 to 48 weeks. Boceprevir and telaprevir are both taken three times a day for a time period ranging from three months to 44 weeks, depending on clinical circumstance for each patient.
The new protease inhibitors increased efficacy — and side effects . Telaprevir is associated with a rash that generally appears in the first four to eight weeks of therapy, as well as anal pain that can manifest at any time during treatment. Most patients are easily treated with topical creams and antihistamine pills. Boceprevir is associated with a bad taste in the mouth in almost all patients — though this is more of an annoyance than a problem. Most patients barely notice it. Both telaprevir and boceprevir are associated with the development of significant anemia, which can limit their use. The anemia can lead to fatigue and may require the use of growth factors — compounds that affect cell growth, maturity and differentiation — to alleviate symptoms.
Since the approval of boceprevir and telaprevir, drug development has been progressing rapidly. Many studies are evaluating the use of second-generation protease inhibitors, polymerase inhibitors and NS5A inhibitors in various combinations to treat all different types of patients with hepatitis C. In addition to new agents, shorter durations of therapy (eight or 12 weeks) and interferon-free, all-oral regimens are in development.
It is highly probable that an all-oral regimen for the treatment of hepatitis C genotype 2 and 3 will become available late this year or in early 2014, with similar efficacy as that of interferon-based therapies, but with fewer side effects and a shorter course. It is also likely that a new, second-generation protease inhibitor — simeprevir — and a first-in-class oral nucleotide analogue polymerase inhibitor — sofosbuvir — will be approved in early 2014.
Both of those new agents are given once daily and will be approved for use in hepatitis C genotype 1 in combination with interferon and ribavirin. The treatment duration for the new simeprevir-containing regimen will likely be 24 to 48 weeks, while the regimen with sofosbuvir will likely last 12 weeks. Neither of those new agents have any significant side effects, and cure rates should be higher than currently approved triple therapies.
After simeprevir and sofosbuvir are approved, many even newer agents are likely to come to market. It seems clear that all-oral therapy for the treatment of genotype 1 should be available sometime in 2015 or 2016. Compared to current regimens, all of the newer therapies offer higher cure rates, shorter duration of therapy and fewer side effects. A lot of work is underway to determine the best possible therapy for specific groups of patients. For example, specific regimens will likely be developed for each genotype, for patients with cirrhosis, for patients with kidney disease and for those who have had a kidney transplant.
With any luck, in the next decade, medical science should be able to treat and cure more than 90 percent of hepatitis C patients. The greater challenge is identifying patients — because most remain undiagnosed — and educating medical providers about the new therapies. Hopefully, the CDC screening guidelines will help. In addition to their other advantages, the newer therapeutic regimens may prevent the development of cirrhosis, liver cancer and the need for liver transplantation. The treatment and cure of hepatitis C will be one of the 21st century's major medical success stories.
Bernstein's disclosures are as follows:
Clinical-trial sponsors: Abbott, BMS, Gilead, Janssen, Vertex, Merck, Genentech
Consultant/speaker bureau: Abbott, Gilead, Janssen, Vertex, Merck
The views expressed are those of the author and do not necessarily reflect the views of the publisher.
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