Keiichi Aoyama

Evaluation of transcatheter arterial embolization with epirubicin-lipiodol emulsion for hepatocellular carcinoma*

SummaryA total of 18 patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) with a 4′-epi-doxorubicin (EDX)-lipiodol emulsion. Infusion of the EDX-lipiodol emulsion (EDX-L) via the hepatic artery was followed by the injection of gelatin sponge in 12 cases. The response and survival of these 12 patients following EDX-L treatment were compared with those of 42 subjects treated with a doxorubicinlipiodol emulsion (DX-L) and those of 23 patients treated by TAE with gelatin sponge (GS) only. In the group treated with EDX-L, nine cases were AFP-positive in sera and four showed a decrease in serum AFP values to less than 10% of the pretreatment level. Seven cases showed a partial response, and nine cases showed no change in the size of the tumor. In the group treated with EDX-L, nine cases are alive, and the oldest has survived for more than 431 days since the treatment. The half-year survival value was 57%, and the 1-year survival value was 49%. These values did not differ significantly from those calculated for the group treated with DX-L. The 1-year survival value determined for patients treated with a lipiodol emulsion (EDX-L or DX-L) followed by GS was 65%, and the 2-year survival value was 39%. These results rates are significantly better than those obtained in patients treated with GS only (1-year survival, 39%; 2-year survival, 13%).

Interaction of lymphocytes with hepatocytes containing hepatitis B antigen: Ultrastructural demonstration of target antigen and T-cell subsets by the peroxidase antibody technique

Hepatitis B virus associated antigens and subsets of lymphocytes in liver tissue were studied using immune electron microscopy to clarify the immune mechanism of hepatocyte lysis in type B chronic hepatitis. Using conventional electron microscopy, infiltrating lymphocytes were observed in direct contact with hepatocytes in areas of piecemeal necrosis and focal necrosis; they showed various types of surface adherence with a contact gap of approximately 20 nm in width. The majority of the hepatocytes that were in contact with lymphocytes could be shown to contain HBsAg and/or HBcAg by immune electron microscopy: HBsAg was localized in the endoplasmic reticulum membranes, in tubular structures, and on the outer coat of Dane particles; HBcAg was observed in the nuclei and in the cytoplasmic matrix of hepatocytes. In some cases HBsAg was observed on the plasma membrane of hepatocyte in contact with lymphocytes. Immune electron microscopy using monoclonal antibodies to subsets of human T-lymphocytes revealed that the lymphocytes in areas of piecemeal necrosis and focal necrosis were predominantly CD 5 or CD 8 positive. In contrast, CD 4 positive cells were infrequently observed in necro-inflammatory regions and Leu 7 positive cells were randomly scattered in the sinusoids away from areas of hepatocyte necrosis. These data suggest that HBsAg is at least one of the target antigens expressed on the hepatocyte membrane possibly enabling cytolytic interaction by cytotoxic T cells in chronic type B hepatitis.

Immunohistochemical investigation of hepatitis B virus associated antigens, HLA antigens and lymphocyte subsets in type B chronic hepatitis

SummaryHLA antigens, hepatitis B virus (HBV)-assodated antigens and lymphocyte subsets in liver tissue from 35 patients with HBs antigenemia were studied using an immunoperoxidase double staining method arid immunoelectron microscopy in order to clarify the immune mechanism of hepatocyte lysis in type B hepatitis. Immune light and electron microscopy using monoclonal antibodies to lymphocyte subsets revealed that infiltrating lymphocytes in the areas of piecemeal necrosis and focal necrosis were predominantly CD8-positive, showing direct contact with hepatocytes. In contrast, CD4(+) cells were infrequently observed in necrotizing inflammatory lesions. HLA-A,B,C antigens were mainly found on hepatocytes in areas of piecemeal necrosis and focal necrosis, in association with CD8(+) lymphocyte infiltration. HLA-DR antigens were demonstrated on a few hepatocytes in the same lesions. In cases of CAH with serum HBeAg positive, HLA-A,B,C, antigens and HBV antigens simultaneously demonstrated on the same hepatocytes. Especially, hepatocytes expressing both HLA-A,B,C antigen and HBsAg on the plasma membrane showed direct contact with CD8(+) lymphocytes. This finding fullfilled the morphological requirements for HBsAg as a target antigen. On the other hand, HBcAg was hardly demonstrated in the liver cell membrane but was demonstrated mainly in the cytoplasm. Compared with the nuclear localization of HBcAg in cases of NSR, cytoplasmic localization of this antigen may be associated with membranous expression of new antigens induced by HBV infection.

Variable Region Usage in T Lymphocytes Infiltrating Liver Tissues of Chronic Liver Diseases

To analyze the T cell repertoire of liver-infiltrating lymphocytes, 35 liver biopsy specimens taken for diagnostic purposes were stained by immunohistochemical technique using monoclonal antibodies (mAb) against CD3, CD8, CD45RO, and CD45RA and seven different variable (V) regions of the T cell receptor (TCR). Major populations of the infiltrating lymphocytes were CD3- and CD45RO- positive cells. The mean percentage (±SD) of Vβ5.1-positive cells was significantly (P < 0.05) higher in chronic hepatitis C (18.2 ± 13.3%, n = 15) than that in either chronic hepatitis B (5.7 ± 6.0%, n = 12) or autoimmune hepatitis (1.3 ± 1.2%, n = 3). In cases with primary biliary cirrhosis, only one case showed a high percentage (66%) of Vβ5.1-positive cells with mean ± SD of 19.3 ± 26.2% (n = 5). The percentages of Vβ5.1-positive cells correlated inversely with the Knodell histological activity index scores in cases with chronic hepatitis C. These data suggest that Vβ5.1-positive T cells may play a regulatory role in the immuno-pathogenesis of chronic hepatitis C.

A case of Gilbert's disease with constitutional excretory defect of ICG.

BSP試験は正常でICG試験が高度の排泄異常を呈したGilbelt病の1例を報告した.症例は35歳の女性で,黄疸を主訴に入院し,血液生化学的検査において,貧血,溶血を認めず,間接型優位の高ビリルビン血症(総ビリルビン:3.3mg/dl,間接ビリルビン:2.4mg/dl)とICG試験で15分停滞率77.5%と高度の排泄異常を示した以外は,肝機能異常を認めなかった.腹部血管造影,腹腔鏡下肝生検などによる検査においても肝に著変を認めなかった.ニコチン酸投与による内因性ビリルビン負荷により,間接型ビリルビンの増加とその持続を認めた.またICG試験より算出した血中ICG消失率は0.014min-1と著しい低値を示し,かつ消失曲線はほぼ直線を示し,ICGの肝細胞への取り込み障害が示唆された.ICG試験で高度の排泄異常を伴うGilbelt病は少なく,本邦では本症例を含め11例報告されているにすぎず,これらをまとめ考察を加えた.