Junko Mori

Recombinant Leukocyte A Interferon Treatment in Patients With Chronic Hepatitis B Virus Infection: Pharmacokinetics, Tolerance, and Biologic Effects

Large doses of recombinant leukocyte A interferon were administered to 20 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis B to study the maximum tolerated dose, its pharmacokinetics, and its antiviral activity. The first group of 5 patients received a constant dose of 36 X 10(6) U/day for 28 consecutive days. When it was well tolerated, the second, third, and fourth groups (5 patients each) received 50, 72, and 100 X 10(6) U/day, respectively. All 20 patients completed the 28-day treatment. Hourly and daily profile of serum interferon level showed a dose-dependent effect with an increasing dosage, and cumulative effects during the treatment. The mean peak serum interferon concentration ranged from 93 U/ml on day 1 in the first group to 1271 U/ml on day 28 in the fourth group. Inhibition of serum deoxyribonucleic acid polymerase activity and hepatitis B virus-deoxyribonucleic acid during the treatment was compared between the groups with low doses (36 and 50 X 10(6) U) and high doses (72 and 100 X 10(6) U). Low doses of interferon suppressed deoxyribonucleic acid polymerase activity to the same extent as did the high doses. Prednisolone withdrawal was combined with interferon in 5 patients. Three patients treated with such combination became seronegative for hepatitis B e antigen during the treatment, whereas all 15 with interferon alone remained seropositive. These results suggest that a maximum antiviral effect of recombinant leukocyte A interferon is below the maximum tolerated doses.

Combination of short-term prednisolone and adenine arabinoside in the treatment of chronic hepatitis B

The efficacy of adenine arabinoside (Ara-A) alone or in combination with prednisolone utilizing its withdrawal effect was studied in 43 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis. Ten patients were treated with 10 mg/kg body wt of Ara-A alone for 4-8 wk. In 9 cases, prednisolone (40 mg/day) was given at a constant dosage for 4 wk before Ara-A treatment. Fourteen patients received oral prednisolone alone for 4 wk, and 10 patients served as untreated controls. Six of 9 patients (67%) undergoing the combination therapy became seronegative for hepatitis B e antigen, whereas only 4 of 24 patients (17%) treated either with Ara-A alone or prednisolone alone lost the antigen. Two of the 10 untreated patients became seronegative for hepatitis B e antigen during the same follow-up period of 9 mo. This prospective controlled study suggests that the combination of immunomodulation by steroid withdrawal and subsequent Ara-A is more effective in the treatment of patients with chronic liver disease and active hepatitis B virus replication than treatment with Ara-A alone.

Correlation of Hepatitis B Virus DNA and Antigens in the Liver A Study in Chronic Liver Disease

Hepatitis B virus deoxyribonucleic acid (DNA) and antigens (HBsAg and HBcAg) were studied in liver biopsy specimens from 105 HBsAg-positive patients with chronic liver diseases. Free or integrated viral DNA, or both, was detected in 83 of 105 (79%) patients, whereas HBsAg and HBcAg were demonstrated immunohistologically in 96 (91%) and 39 (37%), respectively. Of 60 patients with detectable free viral DNA, 38 (63%) were positive for HBcAg, whereas only 1 of 45 (2%) with either integrated viral DNA alone (n = 23) or no detectable viral DNA (n = 22) was positive for HBcAg (p less than 0.001). Furthermore, the amount of HBcAg was positively correlated with the amount of free viral DNA in the liver tissue. In contrast, HBsAg was well expressed not only in the liver with free viral DNA, but also in the liver with integrated DNA. These data suggest that the synthesis of HBcAg is primarily directed by free viral DNA, whereas that of HBsAg may be directed by free as well as integrated viral DNAs.

Delta infection in Japan: Immunohistological and immuno-electron microscopic study of delta antigen in liver tissue

Abstract Although the vast majority of hepatitis B surface antigen (HBsAg) carriers of the world inhabit South‐east Asia, very little is known about delta infection in this area. Therefore, a serological and immunohistological study was made in the Tokyo‐Chiba area. One of 58 (1.7%) HBsAg carriers had anti‐delta antibody in a high titre in serum. Delta antigen was immuno‐histologically localized in the liver in two of 146 (1.4%) HBsAg carriers studied. The antigen was strongly stained in the nuclei, and positive cells were diffusely scattered throughout the liver in both cases. Neither subject was an illicit drug user: one had travelled to Italy 10 years earlier and the other had a blood transfusion during a 5‐year residence in Bangkok in the past.

Immuno-electronmicroscopical study of the delta antigen in liver from an HBsAg carrier.

HBs抗原陽性者140名中に発見されたδ抗原陽性2名のうち1例に酵素抗体法にて免疫電顕的検索を行った.δ抗原は肝細胞核内にのみ染色され,核小体を除く核内に比較的び漫性に見い出されるが核によって染色性の強弱は様々であり,その頻度は45個につき陽性核は1個(2.2%)であった.強拡大では雲状の個々の形態不鮮明なものが主であるが,1部に直径10～20nmの境界不鮮明な顆粒状のものが見られるが明確な形態は認められなかった.細胞質では染色されているものはなかった.各阻止試験組み合せの免疫電顕的検索で,核内に陽性に染色されるものはδ抗原であることを確認した.本邦におけるδ抗原についての免疫電顕的検索は最初である.

Immunohistological study of delta-antigen and anti-delta in hepatitis B virus infection.

HBs抗原陽性者におけるδ感染症を検索する為,本邦慢性肝疾患146例,米国慢性肝疾患21例について酵素抗体法を施行した.δ抗原は,核小体を除く肝細胞核内に明瞭に染色された.本邦例においては146例中2例(1.4%)と極めて低い頻度であったが,米国例においては21例中8例(38.1%)と高率に認められた.本邦におけるδ感染症を認めた2例は,いずれも麻薬,覚醒剤の既往はなく,渡航歴のある点が共通しており,1例は輸血歴を有している.また,両者の肝組織,臨床経過は共に良好であった.現在δに関するassayの確立の為にはδ抗原を含む肝組織が多量に必要であり,我が国においては抗原の入手は容易ではない.今回,我々が施行した酵素抗体法は,現時点において本邦におけるδ感染症のスクリーニングに最も有用である.