Patients with hepatitis C who fail to respond to interferon often have higher levels of liver iron than patients who do respond. Serum transferrin, iron saturation and ferritin frequently are elevated in patients with hepatitis C. Based on these findings, a number of clinical trials have been initiated to examine the role of iron reduction by phlebotomy both in patients naive to interferon therapy, as well as in patients who did not respond to an initial course of interferon therapy.
A recent preliminary study from the University of California at Irvine showed improvement in initial response and sustained response in a group treated with phlebotomy prior to interferon therapy. There is now a multicenter trial in progress in the United States examining the role of iron reduction prior to interferon therapy in patients who have not been previously treated. This study randomizes naïve patients to either iron reduction followed by interferon compared to interferon therapy alone.
There are limited effective therapies currently available for patients who have failed an initial course of interferon therapy. A number of therapeutic options are being examined in these patients. These include repeated therapy with interferon at higher doses, treatment for prolonged periods, and combination therapies. Although there is good data that combination therapy with ribavirin and interferon, and prolonged therapy with interferon may improve the sustained response rate in patients who have not been previously treated, there is little data about the efficacy of these treatments in patients who have failed a course of interferon. Several recent preliminary studies, presented at the annual meeting of the American Association of the Study of Liver Diseases in 1996, suggest that patients who had previously failed interferon therapy have a significant reduction in viral titer and significant reduction in serum biochemical tests such as ALT and AST when they were subsequently treated by iron reduction and then retreated with interferon.
Based on this encouraging preliminary data about the treatment of patients who have failed to respond to interferon therapy, we are currently conducting a study at the University of Washington Medical Center examining the role of phlebotomy in these patients. In this study, which is currently in progress and actively recruiting patients, patients will be seen at the UWMC and undergo weekly or biweekly phlebotomy until they are iron depleted as indicated by serum transferrin saturation, serum ferritin, and hematocrit. Once patients are iron depleted, they are retreated with the highest dose of interferon that they had previously received. Patients are carefully monitored during the phlebotomy period, and serum is collected for measurement of viral level and for markers of inflammation. Most patients with hepatitis C require between 5 and 10 phlebotomies to become iron depleted. Our goal for this study is to enroll 30 to 50 patients at both our site and at two other sites.