Interferon therapy for chronic hepatitis B.
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Biomedical subjects
Publications and source records attributed to W Weimar.
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In a double-blind study human leucocyte interferon was given for six weeks to 8 of 16 patients with chronic HBsAg-positive hepatitis. In the first week 12 x 10(6) reference units were administered daily, and thereafter the dose was halved every week. During the first two weeks leucopenia was observed in 6 of the 8 interferon-treated patients. Apart from a drop in DNA-polymerase activity in the first week, no effect was found on indices of hepatitis-B-virus infection.
In eight patients with biopsy-confirmed chronic active hepatitis (CAH), hepatitis B e antigen (HBeAg) levels and DNA polymerase (DNA-P) activity were assayed three times a week for six weeks and once a week for another six weeks. HBeAg levels were rather constant, whereas DNA-P activity fluctuated. No correlation was observed between the quantities of HBeAg and DNA-P activity. An unexpected fluctuation in DNA-P activity was noted in all patients after an influenza vaccination.
Sixteen patients with hepatitis B antigen (HBsAg) positive chronic active hepatitis (CAH) were vaccinated with the nonhuman influenza A virus Heq1Neq1; eight patients were also treated with leucocyte interferon. Pre-vaccination sera were negative for specific antibody in hemagglutination inhibition tests. Four weeks after vaccination all patients had responded with a homologous antibody titer. Between the interferon-treated and the untreated groups the differences in antibody titers against the vaccine virus were not significant. Concomitant with the antibody response against the nonhuman influenza virus, a fourfold or higher antibody rise was observed against the influenza A virus strains Hsw1N1 (in six treated with seven untreated patients), H1N1 (in six treated and four untreated patients) and H3N2 (in five treated patients only). The results suggest that a normal specific antibody response in HBsAg positive chronic active hepatitis patients is not significantly altered by leucocyte interferon, and that non-specific antibody production can occur in the absence of a serologic relationship.
Rat interferon of relatively high specific activity (about 10(6) units/mg protein) was produced in embryonic rat cells treated with Newcastle disease virus at a high m.o.i. The cells were cultured in serum-free medium and the interferon was precipitated and concentrated with 0.02 M-zinc acetate or with ammonium sulphate at 85% saturation. With both methods the increase in interferon activity was greater than the concentration factor. The rat interferon activity was stable on treatment with 0.15 M-perchloric acid or three cycles of freezing and thawing, but incubation at 37 degrees C for 1 h resulted in a 50% loss in activity. It had no cross activity in human or mouse cells. The sensitivity of different types of rat cells for rat interferon differed widely and was dependent on the challenge virus. Human interferons had no detectable antiviral activity on rat cells and did not block the activity of rat interferon.
The prophylactic antiviral activity of systemically administered human interferon preparations was tested in 36 rhesus monkeys against vaccinia virus injected into the skin. All nine control monkeys developed typical vaccinia skin lesions. Eight of nine monkeys treated with daily intramuscular injections of leucocyte interferon (5 x 10(5) units/kg) from day -1 to day +7 after vaccination were completely protected. No lesions developed after discontinuation of therapy. Administration of the same amounts of leucocytic interferon intravenously (i.v.) was equally effective. Daily intramuscular (i.m.) injections of lower doses of leucocyte interferon (1.25 c 10(5) units/kg; 0.5 x 10(5) units/kg) decreased the severity of the skin lesions. Lesion scores correlated inversely with the dose of interferon. Four of six animals receiving daily i.m. injections of fibroblast interferon (5 x 10(5) units/kg) and one of three animals treated i.v. with the same dose were protected against vaccinia virus, and the lesions in the other monkeys were smaller. Intramuscular injections of 5 x 10(5) units/kg of fibroblast interferon or 1.25 x 10(5) units/kg of leucocyte interferon resulted in comparable serum levels and had comparable efficacy in reducing lesion scores.
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Six patients with hepatitis B surface antigen, hepatitis B 'e' antigen positive chronic active hepatitis, and elevated hepatitis B specific DNA polymerase activity were treated sequentially with fibroblast and leucocyte interferon. Fibroblast interferon induced a fall in serum transaminase activities in all patients, whereas a consistent decline in DNA polymerase activity was observed during leucocyte interferon administration only. After treatment one patient remained persistently DNA polymerase and hepatitis B 'e' antigen negative, whereas relapse to initial values occurred in others. Side effects included severe but reversible granulocytopenia, and chills responding to promethazine treatment. The differential biologies with their non-identity in in vitro studies.
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