Contact: Kara Gavin, [email protected], (734) 764 2220
U-M launches major new investigation of promising hepatitis C therapy
ANN ARBOR, Mich. - The University of Michigan Health System is one of a select group of clinical centers launching a new study for patients with chronic hepatitis C. The study - the longest and largest ever for hepatitis C - will examine the effects of long-term antiviral therapy in potentially slowing or halting the progression of liver disease.
Four million Americans are infected with the hepatitis C virus. It's estimated that 20 percent of those patients will eventually develop cirrhosis, liver failure or liver cancer. More than half of all hepatitis C patients will not respond to current treatment.
"The aim is to identify patients with very advanced liver disease who are much more likely to develop problems," says Anna Lok, professor of internal medicine in the U-M Health System, and principal investigator in the study. "We want to find out if long-term, suppressive treatment might slow down progression of liver disease, and therefore, reduce the risks of complications."
The eight-year study will be conducted at ten clinical centers around the country. It is made possible by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. Subjects chosen for the study will receive long-term therapy with a new preparation of interferon combined with the antiviral drug, ribavirin.
The U-M and each of the other sites are looking to enroll approximately 130 patients over a two-year period who fit the following criteria:
-- Patients with a known diagnosis of hepatitis C who have been previously treated for at least three months and clearly have not responded but were able to tolerate the treatment reasonably well.
-- Patients with significant liver disease, based on liver biopsies. They must either have cirrhosis or be on the verge of developing cirrhosis.
Chronic hepatitis C is currently treated with a 12-month regimen of alpha interferon and ribavirin. Traditionally, if patients do not clear the virus after six months of therapy, the treatment is stopped. Lok and her colleagues believe that some patients may benefit from continued treatment, even if they do not clear the virus.
"There is evidence out there to suggest that some patients could benefit from longer-term treatment, even though they are not cured," says Lok. "Previous studies suggest that some patients have decreased liver damage when liver biopsies are repeated, and other studies have suggested that patients may have a decreased risk of liver cancer."
Patients chosen for the study will receive a baseline liver biopsy to determine the extent of liver disease at the start of the trial. They will then be retreated with the most advanced therapy available - pegylated alpha-2a interferon - plus ribavirin for the first six months.
Pegylated interferon, known as Pegasys, is a long-acting preparation of interferon that is only given once per week, compared to three times weekly with standard therapy. It has a much steadier and consistent drug level, which allows for sustained effects on the virus. Studies have shown that patients tolerate pegylated interferon better than the standard form of the medication.
After the initial six months of treatment, those that have not cleared the virus - estimated to be 70 percent to 80 percent of the study population - will then be randomized into two groups. One set of patients will stop treatment and the other half will continue to receive pegylated interferon only. Both groups will be monitored for 3-and-a half years, with additional biopsies performed at the end of years two and four in the study.
Lok says ribavirin will be discontinued after the initial six months because combination therapy has many side effects and there is not enough safety data available for long-term use.
Interferon works largely by decreasing virus replication. There also is some data that suggests interferon may work to reduce liver fibrosis. Lok says this is a key component to the study because it's usually fibrosis that ultimately proceeds to cirrhosis. Ribivarin is a weak antiviral compound. It's not very effective by itself, but when combined with interferon, it appears to enhance the effect of interferon in treating hepatitis.
Hepatitis C is a disease caused by the hepatitis C (HCV) virus which results in an inflammation of the liver. It is usually transmitted through blood-to-blood contact between two people, most commonly by sharing of needles. Transmission through transfusion of contaminated blood or blood products has become rare since the development of sensitive screening tests in the early 1990s. Transmission through sexual contact or from infected mothers to their babies may also occur, but the risk is low.
The Centers for Disease Control and Prevention estimates that hepatitis C costs more than $600 million dollars in medical bills and lost work each year.
Lok's co-investigator at the U-M is Robert Fontana, M.D., assistant professor of internal medicine.
More information on the study is available by calling 1-877-452-4813 or on the Internet at http://www.med.umich.edu/intmed/hepbc
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