Lamivudine-high dose interferon combination therapy for chronic hepatitis B patients co-infected with the hepatitis D virus

Currently, the best option for patients with hepatitis delta is interferon alpha therapy for at least one pear. To evaluate the effect of the combinat ion lamivudine-high-dose interferon alpha therapy, we first treated eight p atients with chronic hepatitis delta infection with lamivudine for at least 24 weeks; then lamivudine was combined with a high dose of interferon alph a followed by a regular dose (9 MU tiw). Follow-up was 12 weeks. Virologica l, biochemical and histological features were evaluated for response to the rapy. At baseline, all patients were HBsAg positive in serum and HDV RNA-(P CR)positive in plasma: HBV DNA was undetectable with the Digene Hybrid Capt ure assay (limit of detection 1.5 x 10(6) geq ml(-1)) in all cases. Transam inases were elevated in all patients: median ALT 68 (range 48-143) IU I-1. Seven of eight patients completed the course: one patient with a pre-existi ng sickle cell trait was withdrawn from the trial due to the development of a nephrotic syndrome. The HBsAg-concentration in serum decreased in two ou t of seven patients (29%), However, there was no significant decrease in th e HBsAg-concentration in serum during treatment (median 3654 PEU l(-1) (ran ge 548-7684) to 5300 PEU l(-l) (range 168-19639)). The drop of HDV RNA in p lasma from baseline during treatment was not significant. Decrease of HDV R NA 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 decre ased in three other patients (improvement in 57%), However, three of these four patients showed a rebound after withdrawal of therapy. The Histology A ctivity Index (HAI) indicated a drop from a median score of 7 (range 5-9) a t baseline to 5 (range 3-8) at the end of treatment, but an increase in fib rosis 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.