Update on Treatment Options

Dr. Jensen received his M.D. from the University of Illinois College of Medicine in 1972. He completed an internship and residency in internal medicine at Rush-Presbyterian-St. Luke’s Medical Center, Chicago, in 1975 and served there as Chief Medical Resident in 1975-76. From 1976-78 he was the Pillsbury Liver Research fellow at King’s College Hospital in London, England, under the direction of Dr. Roger Williams.

In 1978, Dr. Jensen became a member of the Section of Digestive Diseases at Rush Medical Center, Chicago. In 1992, he was appointed to the position of Director of Clinical Hepatology, and in 1996, he was made Director of the newly created Section of hepatology at Rush.

Dr. Jensen is a member of many medical societies and is a Fellow in the American College of Physicians. He has served on committees for the Federated Societies of Gastroenterology and Hepatology and on the Hepatitis Educators Committee of the American Digestive health Foundation. He is a past-president of the Chicago Society of Gastroenterology, a board member of the Chicago chapter of the ALF, and a founding board member of the Chicago Liver Group and the National Transplant Society. He is a member of the Hepatitis Advisory Panels for F. Hoffmann-La Roche, Ltd. and Amgen pharmaceuticals.

Dr. Jensen has published over 60 articles in the medical literature, and is currently principal investigator for over 15 clinical trials in the treatment of hepatitis B and C.

Treatment with standard interferon 3MU three times weekly for 12 months achieves sustained virological response rates of only 10 to 20% and is associated with significant adverse events. Indeed, dosage reduction is necessary in 0 to 40% of patients receiving standard interferon and treatment is discontinued in 5 to 15% of patients. Because of these less-than-optimal sustained response rates, there is an impetus to develop more effective treatments for patients with HCV infection.

Increasing the dose and duration of standard interferon can improve response rates at the end of treatment, but relapses are still frequent. A number of recent studies have shown that response rates can be improved with the addition of ribavirin to standard interferon therapy, with rates of sustained virological response approaching 40%. Indeed the FDA recently approved a combination drug (ribavirin and interferon alfa-2b recombinant) for the treatment of certain hepatitis C patients. In a recent trial, 24 or 48 weeks of treatment with standard interferon in combination with ribavirin produced significantly higher sustained response rates than interferon alone 931 and 38%; p <0.01 vs. 13 and 6%; p <01 for 24 and 48 weeks of treatment, respectively) in patients with HCV infection who had not previously received interferon treatment. Similarly, 24 or 48 weeks of treatment with standard interferon plus ribavirin produced significantly higher sustained response rates than interferon alone (49 vs. 5% p < 0.001) in-patients who had relapsed following previous interferon treatment. The addition of ribavirin to standard interferon increases the risk of anemia as well as the number of dosage reductions and patient withdrawals relative to that of standard interferon alone.

An investigational pegylated interferon possessing a longer half-life than standard interferon has recently been developed. The pharmacokinetic and pharmacodynamic properties of this product enable it to be administered once weekly to maintain consistent and sustained antiviral pressure on the HCV virus. Preliminary results from Phase II trials suggest higher sustained virological response rates with pegylated interferon than those observed with standard interferon in patients with chronic HCV infection without cirrhosis. This was an ascending-dose study of pegylated interferon 45, 90, 180 and 270 ug weekly in comparison with standard interferon (n = 155). The treatment period was 48 weeks, with a follow-up at 24 weeks after the end of treatment. Sustained response rates increased stepwise with higher doses of pegylated interferon, and appeared to plateau at the 180 ug dose. Pegylated interferon had an adverse event profile similar to that of standard interferon. Interim data from a large multicenter Phase III trial supports similar tolerability. Early data from studies combining pegylated interferon with ribavirin are also encouraging. Virological response rates with this combination are 80% (16/20). Larger clinical trials with this compound are underway.

SUGGESTED READING

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Bennett WG, Inoue Y, Beck R, Wong JB, Pauker SG, Davis GL. Estimates of the cost-effectiveness of a single course of interferon-a2b in patients with histologically mild chronic hepatitis C. Ann Intern Med 1997;127:855-65.

Bruno S, Silini E, Crosignani A, Borzio F, Leandro G, Bono F, Asti M, Rossi S, Larghi A, Carino A, Podda M, Mondelli MU. Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study. Hepatology 1997;25:754-8.

Centers for Disease Control. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV ­ related chronic disease. MMWR Morb Mortal Wkly Rep 1998;47 (No. RR-19):1-39.

Davis GL, Esteban-Mur R, Rustgi V, Hoefs J, Gordon SC, Trepo C, Shiffman ML, Zeuzem S, Craxi A, Ling MH, Albrecht J. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. N Engl J Med 1998;339:1493-9.

Foster GR, Goldin RD, Thomas HC. Chronic hepatitis C infection causes a significant reduction in quality of life in the absence of cirrhosis. Hepatology 1990;27:209-12.

Gretch DR. Diagnostic tests for hepatitis C. Hepatology 1997;26:43S-7S.

Hopf U, Berg T, Konig V, Kuther S, Heuft HG, Lobeck H. Treatment of chronic hepatitis C with interferon alpha: long-term follow-up and prognostic relevance of HCV genotypes. J Hepatol 1996;24(2 Suppl):67-73.

Idilman R, De Maria N, Colantoni A, Dokmeci A, Van Thiel DH. Interferon treatment of cirrhotic patients with chronic hepatitis C. J Viral Hepat 1997;4:81-91.

Karino Y, Toyota J, Sugawara M, Higashino K, Sato T, Ohmura T, Suga T, Okuuchi Y, Matsushima T. Early loss of serum hepatitis C virus RNA can predict a sustaineed response to interferon therapy in patients with chronic hepatitis C. Am J Gastroenterol 1997;92:61-5.

Kim WR, Poterucha JJ, Hermans JE, Therneau TM, Dickson ER, Evans RW, Gross Jr JB. Cost-effectiveness of 6 and 12 months of interferon ­ a therapy for chronic hepatitis C. Ann Intern Med 1997;127:866-74.

Lee WM, Reddy KR, Tong MJ, Black M, van Leeuwen DJ, Hollinger FB, Mullen KD, Pimstone N, Albert D, Gardner S. Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis C. Hepatology 1998;28:1411-5.

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McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 1998;339:1485-92.

Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, Heathcote J, Zeuzem S, Trepo C, Albrecht J. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet 1998352:1426-32.

Schlaak JF, Trippler M, Ernst I, Meyer zum Buschenfelde KH, Gerken G. Chronic Hepatitis C: the viral load per liver cell before treatment as a new marker to predict long-term response to IFN-alpha therapy. J Hepatol 1997;27:917-21.

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