Longer, More Aggressive Interferon Regimens Best Strategy Against Chronic HCV Infections

NEW YORK--Aggressive new interferon (IFN) treatment strategies aimedat combating chronic hepatitis C virus (HCV) infection are roughly twiceas effective as the standard thrice-weekly, six-month IFN regimen.

"A 12-month to 18-month course of Intron A [IFN alfa-2b] nearlydoubles the sustained response among HCV patients," Robert G. Gish,MD, said during a press briefing funded by an educational grant from ScheringOncology Biotech.

Dr. Gish is medical director of the Liver Transplant Program at theCalifornia Pacific Medical Center, San Francisco.

Left untreated, HCV infection can result in cirrhosis, and once cirrhosishas begun, current treatment regimens are unlikely to clear the virus,he said. However, recent data suggest that treating HCV-infected cirrhoticpatients with IFN may decrease their risk of developing liver cancer anddelay the time to death or transplantation. Thus, he suggests aggressiveIFN therapy for patients with early cirrhosis.

"Among cirrhotic patients with liver cancer, the five-year survivalrate is only about 5% to 20%," Dr. Gish said. However, patients withthis lethal disease combination have approximately an 80% survival rateif liver transplant is performed. Unfortunately, many of these patientsare not candidates for transplant because their liver tumors exceed 10cm.

Overall, he said, the management of HCV infection is promising givenIFN's proven efficacy and new combination treatments. Slow-release polyethyleneglycol (PEG)-bound IFN formulations under development may prove useful,since they offer a convenient once- or twice-weekly dosing schedule.

Combination HCV Therapies Emerging

Ribavirin (Virazole), a guanine nucleoside analog approved in the USfor use as a pediatric aerosol treatment for respiratory syncytial virus,is now being evaluated in combination with interferon alfa-2b (Intron A)for HCV treatment.

Although the mechanism for the favorable synergistic effect is not yetunderstood, there appears to be an immunomodulatory action that maintainsor stimulates cell-mediated immune function.

Approximately 40 US trials of the combination are underway in HCV patientswho failed conventional IFN therapy. One study of 50 IFN-naïve HCVpatients, presented at the press conference by Douglas Dietrich, MD, ofNew York University, showed that combination therapy doubled the responserate, compared with IFN alone.

After six months of treatment, 52% of patients in both groups had nodetectable HCV. After another six months of follow-up, 36% of those receivingcombination therapy remained without detectable viral levels versus 18%of the mono-therapy patients.

Said Dr. Gish: "HCV therapy must be started early in the diseaseprocess, be aggressive, and continue for the long-term. It is importantfor all physicians to realize that this approach will improve survival,and even cure the disease in many cases."