Currently, the best option for patients with
hepatitis delta is
interferon alpha therapy for at least one year. To evaluate the effect of the combination
lamivudine-high-dose
interferon alpha therapy, we first treated eight patients with
chronic hepatitis delta infection with
lamivudine for at least 24 weeks; then
lamivudine was combined with a high dose of
interferon alpha followed by a regular dose (9 MU tiw). Follow-up was 12 weeks. Virological, biochemical and histological features were evaluated for response to
therapy. At baseline, all patients were
HBsAg positive in serum and HDV
RNA-(PCR)positive in plasma; HBV
DNA was undetectable with the Digene Hybrid Capture assay (limit of detection 1.5 x 10(6) geq ml-(1)) in all cases.
Transaminases were elevated in all patients; median ALT 68 (range 48-143) IU l(1). Seven of eight patients completed the course; one patient with a pre-existing
sickle cell trait was withdrawn from the trial due to the development of a
nephrotic syndrome. The
HBsAg-concentration in serum decreased in two out of seven patients (29%). However, there was no significant decrease in the
HBsAg-concentration in serum during treatment (median 3654 PEU l(-1) (range 548-7,684) to 5300 PEU l(-1) (range 168-19,639)). The drop of HDV
RNA in plasma from baseline during treatment was not significant. Decrease of HDV
RNA was observed in three out of seven patients (43%) (median 10(5) geq ml(-1); range 10(3)-10(6) to median 10(3) geq ml(-1); range 10(2)-10(7)). Serum ALT did not change as reflected by a median of 68 IU l(-1) (range 48-143) at start of
therapy to 63 IU l(-1) (range 20-171) at the end of
therapy. At the end of treatment
transaminases had normalised in one patient and decreased in three other patients (improvement in 57%). However, three of these four patients showed a rebound after withdrawal of
therapy. The Histology Activity Index (HAI) indicated a drop from a median score of 7 (range 5-9) at baseline to 5 (range 3-8) at the end of treatment, but an increase in
fibrosis from a median grade of 2 (range 1-3) at baseline to 3 (range 1-4) at the end of treatment was observed. In conclusion, this study does not yield support for the combination of an HBV suppressor and 16 weeks of high-dose
interferon for
therapy aimed at eradicating the hepatitis delta virus.