Sir,- Dr. Caselmann and colleagues (August 22, p 454) report a trial of a combination of IFN-ß and IFN-y in chronic active hepatitis B (CAH). We are currently doing a trial of combined administration of recombinant interferons alpha (rIFN-alpha) and gamma (rIFN-y) in hepatitis B virus (HBV) chronic carriers.
40 HBsAg, HBeAg and HBV-DNA positive patients with histologically proven CAH were randomly allocated to one of the following groups (n=8 per group): (I) 10 MU/m2 rIFN-alpha (Boehringer Ingelheim) 6 months; (II) 2 MU rIFN-y under the same comditions; (III) 10 MU/m2 rIFN-alpha for 3 months and then 2 MU/m2 rIFN-y for another 3 months; (IV) simultaneous administration of 5 MU/m2 rIFN-alpha and 1 MU/m2 rIFN-y over 6 months; and (V) control group without treatment, In all treated patients IFN was administrated twice weekly by intramuscular injection.
All patients finished the treatment and no intolerable toxicity was observed in any of the groups. At the end of the treatment period 7 treated patients (2 from group I, 2 from group II, and 3 from group III) were HBV-DNA negative while only I of the controls became negative to this marker. During follow up, another 4 patients lost HBV-DNA (1 from group III, and 3 from gropu IV). A total of 4 control patients became HBV-DNA negative. After a year 4 treatedpatients were HBeAg negative (1 from grupo I, 1 from group III, and 2 from group IV). At that time, none of the controls were HBeAg negative. In all patients who became HBV-DNA an HBeAg negative alanine aminotransferase levels fell to normal or near normal.
These preliminary results suggest that combined therapy with rIFN-alpha and rIFN-y is well tolerated and seems to give better results than when only one type of rIFN-alpha and rIFN-y has a more delayed antiviral effect than that observed when rIFNs are used in two cycles.
In other trials in our department, the antiviral efficancy of rIFN-alpha and rIFN-y in the treatment of chronic hepatitis B has been demonstrated. With doses of 10 or 20 MU of rIFN-alpha twice weekly for six months, 7 of 12 patients responded. In two other controlled studies different rates of response were obtained: 2/9 (22%) and 6/18 (33%). With rIFN-y therapy in a pilot study we observed a significant antiviral effect on HBV replication during the treatment period when 2 or 5 MU rIFN-y per day were administered intramuscularly for 28 days.
As Caselmann and colleagues propose, we think that tha combination of IFNs may give better results than when only one agent is administered. However, we believe that further studies, probably in a thrice weekly schedule, with combinations of rIFN compared with monotherapy, should be done.