Fumihiro Ichida

Propagation of hepatitis A virus in hybrid cell lines derived from marmoset liver and Vero cells.

To establish monkey liver cell lines with a high susceptibility to hepatitis A virus (HAV), marmoset (Saguinus labiatus) liver cells were fused with Vero cells deficient in hypoxanthine-guanine phosphoribosyltransferase and the resulting hybrid cells were selected in HAT medium. Of four hybrid cell lines obtained (S. 1a/Ve-1 to -4), three (S. 1a/Ve-1, -3 and -4) were equally susceptible to HAV infection. When inoculated with a virus isolated from marmoset liver tissue (10% liver tissue extract) or a faecal virus (10% stool extract) from a human hepatitis A patient, all susceptible cell lines showed a significant elevation of viral antigen activity as seen in radioimmunoassay and/or immunofluorescent antibody assays, at 4 to 6 weeks post-infection (p.i.) with the liver-derived inoculum and at 6 to 8 weeks p.i. with the stool-derived inoculum. In S. 1a/Ve-1 cells, a representative of the susceptible hybrid cell lines, full adaptation of HAV (liver tissue virus concentrate) to cell culture was attained after four serial passages. Thereafter, the virus grew to a plateau titre of 10(8.5) TCID50/ml at 7 days p.i. in a growth experiment. The infected cells showed no cytopathic effects but eventually a persistent infection was established when a saturated level of virus growth was reached.

Effect of the Polysaccharide Sizofiran, an Immunotherapeutic Agent, on HBeAg-positive Chronic Hepatitis

In two clinical studies with 155 subjects, we investigated the polysaccharide Sizofiran (SPG) for its efficacy and optimal dosage as an immunotherapeutic agent in patients with chronic hepatitis B. Hepatitis B e antigen (HBeAg)-positive patients were given 20 mg, 10 mg, 5mg or 1 mg of SPG intramuscularly once a week for 16 weeks. In the first study, 9 of 25 patients (32.1%) receiving 10 mg became seronegative for HBeAg during the follow-up period of 6 months. In the second study, treatment with SPG was effective in 5 of 25 patients (20.0%) on 10 mg during the follow-up period of 3 months. Response rates were significantly lower for all other dose groups. Thus polysaccharide SPG appears to be effective in some patients with chronic hepatitis B and its optimal dose is estimated to be 10 mg once a week.

Anti-HCV in the medical employees comparison to the voluntary blood donors.

Anti-HCV were tested in 6, 093 voluntary blood donors (male 3, 842, female 2, 251) and 566 medical employees (doctors 219, nurses 297, technologists 50) using ELISA Kit of Ortho Diagnostic Systems Co.In voluntary blood donors, percentage of anti-HCV positivity over 36-year-old was statisticaly higher than that under 35-year-old. It is supposed that this phenomena was caused by the improvement of circumstances of common health and exchanging needls every person in preventive inoculation.In medical employees there is no statistical difference between doctors, nurses technologists and blood donors.In 6 cases anti-HCV positive in ELISA methods, only 3 cases were positive in RIA methods.

Histological Classification of Chronic Hepatitis in Japan

Histological characteristics of chronic hepatitis are described here according to Inuyama classification which is usually used in Japan. It is compared with Fogarty and European classification and discussed. In all of these classifications, not only the cases showing histological picture of classic chronic hepatitis (fibrosis in the portal area and inflammatory infiltration of small round cells) but also the cases which show no fibrosis in the portal area but has inflammation for 6 months or more are defined as chronic hepatitis.

A case of argininosuccinate synthetase (ASS) deficiency diagnosed by the measurement of ASS with the liver biopsy specimen

症例は43才の男性で,意識障害を主訴に,新潟大学附属病院に入院となった.血液検査では,肝機能異常は認められなかったが,血中アンモニアが高値であった.脳波では,典型的な三相波が認められた.経皮経肝門脈造影でも,大循環系との側副血行路は認められなかった.尿中および血中アミノ酸分析を施行したところシトルリンの高値を認めた.腹腔鏡下肝生検にて, argininosuccinate sythetase (ASS)の欠損を認めたが,他の四つの尿素サイクル関連酵素は,正常範囲であった.死亡後,剖検腎にてASS活性を調べたところ,正常であり, ASS欠損症TypeIIと診断された.治療は, 1日40g以下の蛋白制限と,分岐鎖アミノ酸製剤や安息香酸Naの投与を行ったが,効果を示したのは初期のみで次第に効かなくなり,発症より約5カ月後に,高度の脳浮腫を合併して,死亡した.

Studies on intrahepatic localization of pre-S2 antigen in various patients with chronic HBV infection.

B型慢性肝炎79例の肝生検組織87標本について連続切片を作製し,pre-S2抗原,HBs抗原ならびにHBc抗原をPAP法で検索した.87例の肝組織標本中pre-S2抗原は70例,HBs抗原は71例,HBc抗原は49例で陽性であった.肝細胞内におけるpre-S2抗原の局在様式は,HBs抗原と同様に細胞質び漫型,封入体型,膜型の3つのパターンを呈した.pre-S2抗原は,HBs抗原が染色された71標本中70標本で観察ができ,さらにそのうち69標本では,HBs抗原と同様の組織内分布および細胞内局在様式を示した.肝組織中のHBc抗原の有無およびその局在様式は,血中HBe抗原・抗体およびDNAPとの関連が認められたが,pre-S2抗原およびHBs抗原の分布ならびに局在は,HBe抗原・抗体,DNAP活性との間に関連性は認めなかった.

An autopsy case of Caroli's disease followed up for long term.

長期にわたる肝組織所見の推移を観察し得たCaroli病の1例を経験したので報告する.症例は54才の女性で,幼小児期より腹痛発熱発作を繰り返し,昭和54年肝胆道系の精査のため当科を受診した.入院時尋常性乾癬と胆道感染の所見がみられ,各種画像検査所見で肝内胆管の多発性の嚢胞状拡張と門脈圧亢進所見を認めた.その後Caroli病として経過を観察したが,昭和59年より肝性脳症がみられるようになり,昭和60年急性腎不全を併発し死亡した.剖検肝の組織標本では先天性肝線維症に類似した所見を認めたが, 21年前の外科的肝生検組織では先天性肝線維症に特徴的な線維化像は認められず,本例はCaroli病の純型から二次的な線維化により先天性肝線維症合併型に類似した臨床病理所見を呈するようになったものと推測した.

Genetic factors in the pathogenesis of chronic liver diseases

慢性肝疾患の発症における免疫遺伝的因子の関与を検討するため,慢性肝炎(活動性)30例,肝硬変20例を対象にHBs抗原,自己抗体,およびHLA抗原の関連性を検索した.その結果,HBs抗原陽性の慢性肝疾患ではHLA-B7が高頻度にみられたがHBs抗原陰性の場合は特定のHLA抗原との関係は証明されなかった.また慢性肝疾患を自己抗体の有無で検討すると自己抗体陰性群でHLA-B7の頻度が増加していた点が注目されるが,その意義は不明である.一家系例のgenotype解析結果からも慢性肝疾患と免疫遺伝的因子の関連性が強く示唆された.

Hypoglycemia in Primary Hepatocellular Carcinoma with Multiple Pulmonary Metastasis

症例は36歳の男.昭和50年2月,心窩部痛を主訴として某医を受診.肝腫大とともに,胸部レ線で両肺野に多数の腫瘍陰影を発見されたため当科へ精査入院した.入院時,自覚症状はなく,理学所見では肝脾腫と肺呼吸音の減弱を認めた.血清Al-Paseとγ-GTPの上昇,HBs抗原およびAFP陽性,肝シンチグラム,腹腔動脈撮影などから原発性肝細胞癌と診断.各種抗癌剤を使用したが,肺腫瘍陰影は徐々に増大.第49病日に最初の低血糖発作が出現した.この時の空腹時血糖は38～56mg/dlと低値であり,血中IRIは40μU/ml,血中IRGは3,300pg/mlを示した.その後,低血糖発作は頻発し,全身衰弱のため6月死亡.剖検所見では肝右葉に手拳大の主腫瘍が存在し,組織学的には原発性肝細胞癌(Edmondson II)であった.また,両側肺にレ線に一致する多数の転移巣を認めたが,膵組織に著変はなかった.なお,腫瘍中にIRIは検出されなかった.

Symposium (IV): Factors affecting the prognosis of chronic hepatitis

In 45 cases with chronic hepatitis and 40 cases with liver cirrhosis, prothrombin time (PT), thrombotest (TT) , normotest (NT) and blood coagulation factors I I , V, V I I , V I I I , IX, X were determined, and the comparat ive study to liver function tests, histological findings and the course of diseases was done. The following results were obtained. 1) In chronic hepatitis, the changes of N T and T T was paralled to liver function tests, especially S-GOT. 2) In chronic hepatitis, the blood coagulation tests and factors except factor V I I I showed lower level in active type than in inactive type. 3) The blood coagulation levels except factor V I I I were lower in incompensatory liver cirrhosis than in compensatory liver cirrhosis and chronic hepatitis, and the levels decreased with progress of hepatic damage. 4) The blood coagulation levels were lower in the cases of post-hepatitic cirrhosis that developed from chronic hepatitis in early t ime than in late time. 5) Therefore, it is believed that the determination of blood coagulation in chronic hepatitis is usefull to foresee the prognosis of the diseases.