TREATMENT OF CHRONIC HEPATITIS-D WITH INTERFERON-ALFA-2A

Background and Methods. Chronic hepatitis D is a severe and rapidly pr ogressive liver disease for which no therapy has been proved effective . To evaluate the efficacy of treatment with interferon, we studied 42 patients with chronic hepatitis D who were randomly assigned to recei ve either 9 million or 3 million units of recombinant interferon alfa- 2a (three times a week for 48 weeks) or no treatment. Results. By the end of the treatment period, serum alanine aminotransferase values had become normal in 10 of 14 patients receiving 9 million units (71 perc ent), as compared with 4 of 14 treated with 3 million units (29 percen t, P = 0.029) and 1 of 13 untreated controls (8 percent, P = 0.001). S even patients treated with the higher dose of interferon (50 percent) had a complete response (normal levels of alanine aminotransferase and no detectable serum hepatitis delta virus [HDV] RNA), as compared wit h three of those who received the lower dose (21 percent, P = 0.118), and none of the controls (P = 0.004). Treatment with 9 million units o f interferon was associated with a marked improvement in the histologi c findings (reduced periportal necrosis and portal and lobular inflamm ation), whereas in the untreated controls there was considerable histo logic deterioration. In 5 of the 10 patients treated with 9 million un its of interferon whose alanine aminotransferase values became normal, the biochemical responses persisted for up to 4 years (mean, 39 month s), but the effects of treatment on viral replication were not sustain ed. In contrast, none of those who received 3 million units and none o f the untreated controls had a sustained biochemical or virologic resp onse. Conclusions. In about half the patients with chronic hepatitis D treated with high doses of interferon alfa-2a (9 million units three times a week for 48 weeks), the serum alanine aminotransferase level b ecomes normal, HDV RNA becomes undetectable in serum, and there is his tologic improvement. However, a relapse is common after treatment has been stopped.