Hirohiko Abe

Light microscopic findings of liver biopsy specimens from patients with hepatitis type A and comparison with type B.

We compared the light microscopic features of liver biopsy specimens taken within 15 days of onset of symptoms from 17 patients with serologically verified hepatitis type A and 10 patients with serologically verified hepatitis type B. On admission, patients with hepatitis type A experienced higher serum transaminase concentrations and lower total serum bilirubin concentrations than patients with type B. On examination of H & E preparations, specimens from both type A and type B displayed simultaneous hepatocellular degeneration, parenchymal and portal tract inflammatory cell infiltration, and sinusoidal lining cell activation. Hepatitis type A was characterized by conspicuous, mononuclear inflammatory cell infiltration of the portal tract with frequent disruption of the limiting plate, and periportal hepatocyte focal necrosis with virtual sparing of parenchyma about the central vein tributary. Specimens from 10 patients also displayed mild cholestasis. In contrast, hepatitis type B was characterized by modest portal tract infiltration, and extensive parenchymal changes and infiltration, particularly about the central vein tributary.

The extracellular matrix in hepatocellular carcinoma shows different localization patterns depending on the differentiation and the histological pattern of tumors: immunohistochemical analysis

This study investigated cells producing type I, III, and IV collagens, laminin, and fibronectin, the major components of the extracellular matrix, and compared their localization patterns in relation to the grade of tumor differentiation and the histological pattern of hepatocellular carcinoma. Type I, III, and IV collagens, laminin, and fibronectin were produced by tumor, endothelial, and Ito cells. Regarding their localization pattern in relation to the histological pattern of tumors, although the extracellular matrix was present in the subendothelial spaces of sinusoids in every histological pattern, the localization of these components in the intercellular spaces of tumor cells was most marked in hepatocellular carcinoma with a compact pattern. These results suggest that the extracellular matrix produced by tumor, endothelial, and Ito cells is deposited in appropriate positions in hepatocellular carcinoma to sustain the tissue structure showing different histological patterns. In relation to the grade of tumor differentiation, in most cases, Type I, III, and IV collagens and fibronectin were present in the subendothelial spaces of sinusoids and the intercellular spaces of some tumor cells, while little laminin was observed in well-differentiated small hepatocellular carcinoma (less than 10 mm diameter). In undifferentiated hepatocellular carcinoma, little extracellular matrix was observed, except around vessels. These results suggest that sinusoidal capillarization may not yet have occurred in the early stage of hepatocarcinogenesis, although it develops as the tumors increase in size and the tumor cells dedifferentiate. In undifferentiated hepatocellular carcinoma, tumor cells are too atypical to produce each extracellular matrix component.

Antithrombin III concentrate in the treatment of fulminant hepatic failure.

SummaryTwenty-six patients with fulminant hepatic failure were treated with daily infusions of antithrombin III concentrate until recovery of consciousness or death. Seven patients were alive (group A), 7 survived 17 to 47 days after treatment (group B), and 12 died within 9 days (group C). Decreased plasma antithrombin III levels increased on the day after treatment, irrespective of the pretreatment levels in all patients. Continuous or temporary normalization was seen in all patients in groups A and B, but in only 5 in group C patients whose bleeding was extensive (p<0.05). An abrupt drop in peripheral platelet counts occurred when plasma antithrombin III levels were below normal. General bleeding accompanied this drop. These results suggest that maintained normal plasma antithrombin III levels are beneficial for prolonged survival time in fulminant hepatic failure, probably through controlling intravascular coagulation, and that antithrombin III infusion may be useful for such treatment.

Severe alcoholic hepatitis successfully treated by leukocytapheresis: a case report.

BACKGROUND The prognosis of severe alcoholic hepatitis is poor, and there is no established method for a cure. METHODS A 34-year-old man was admitted to Kurume University Hospital because of severe liver dysfunction due to excess alcohol intake. He was treated with prednisolone and two sessions of granulocyte and monocyte adsorption apheresis (GCAP) using an Adacolumn, which removes leukocytes--especially granulocytes and monocytes--from the peripheral blood. We evaluated the changes in the serum levels of interleukin-6, interleukin-8, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule-1, as well as the conventional liver tests and peripheral white blood cell count. RESULTS Prednisolone was effective in the short term but resulted in an increase in C-reactive protein (CRP), peripheral leukocytes, and serum total bilirubin. GCAP performed on the 34th and 41st hospital days produced decreases in the white blood cell count, total bilirubin, and intercellular adhesion molecule-1. The patient survived, despite the expected poor prognosis on admission. CONCLUSIONS GCAP is recommended as a potential therapeutic option for severe alcoholic hepatitis.

Ultrastructural observation on hepatocellular carcinoma

In 31 cases of hepatocellular carcinoma, electron microscopic observation and morphometry on the cell organelles were carried out to evaluate the usefulness of electron microscopy for the diagnosis of well differentiated hepatocellular carcinoma. The cell organelles in well differentiated tumor cells were very similar to those in normal hepatocytes or hepatocytes with liver cirrhosis (LC). We found that in poorly differentiated tumor cells, the nuclear area, N/C ratio, nucleolar area, the amount of dispersed chromatin, and the number of free ribosomes had increased, but the cellular area, degree of nuclear roundness, and mitochondrial area had decreased. These results seem to indicate that electron microscopy is not as useful as light microscopy in the diagnosis of well differentiated hepatocellular carcinoma, but is useful in the study of poorly differentiated tumor cells, which indicated that the cell proliferation through mitoses was activated.

MRI in thorotrastosis

Magnetic resonance imaging (MRI) and computed tomography (CT) were performed in four patients with thorotrastosis. On CT scan, Thorotrast (thorium oxide) deposition was shown as high-density areas in the liver and spleen and the abdominal lymph nodes. These deposits were not found on MRIs. Splenic volume was significantly small due to atrophy. The contrast-noise ratio in the spleen on T1-weighted images was significantly lower. Thorotrast deposition does not affect MRI appearance; therefore it may be useful for the early detection of malignant tumors as a complication of thorotrastosis.

Incidence of anti-HTLV-1 antibody in liver disease

SummaryPositivity for serum anti-HTLV-1 antibody (anti-HTLV-1) in 171 patients with various chronic liver diseases and 22 asymptomatic hepatitis B virus (HBV) carriers was compared with that of 200 healthy controls in the Chikugo district of Japan. The rate of anti-HTLV-1 positivity in patients with liver disease was 8.1% (14/171) and was higher than that (3.5%: 7/200) in healthy controls, but the difference was not significant. However, in patients with liver disease with a history of blood transfusion, the positive rate was 18.4% (7/38) which was significantly higher than that for healthy subject (P< 0.001). On the other hand, in 133 liver disease patients without blood transfusion, anti-HTLV-1 positivity was significantly higher (P< 0.05) in patients with hepatitis B surface antigen (11.3%: 6/53) than in those without it (1.3%: 1/80). These data suggest that the high incidence of anti-HTLV-1 in our patients with liver disease was due to the transmission of HTLV-1 by the same routes (maternal transmission and blood transfusion) and probably at the same time as the hepatitis viruses (HBV and hepatitis C virus).

Efficacy of flumazenil, a benzodiazepine antagonist, in patients with alcoholic liver cirrhosis complicating hepatic encephalopathy.

近年, 肝性脳症患者の血中に増加したベンゾジアゼピン様物質が, 肝性脳症の一因をなすという報告がある. また, 国外では肝性脳症に対しベンゾジアゼピン拮抗薬が投与され, さらにdouble blind studyで評価がなされている.アルコール性肝硬変に伴う肝性脳症10例に対し, ベンゾジアゼピン拮抗薬であるフルマゼニルを単回投与し, 前後での意識レベルと脳波を検討し, その有用性を検討した. 意識レベルの変化では10例中6例 (60%) に改善を認めた. 6例中2例は改善後再悪化なく, 残り4例は30分から2時間の一時的な改善にとどまった. 脳波の改善は, 10例中6例 (60%) に認めた. フルマゼニルの投与は基礎にある肝障害の根本的治療ではないが, 肝性脳症の治療の一つとして, 評緬できるものと考える.

Serum type III procollagen N paptide(PIIIP) and laminin levels and hepatic immunohistochemical study in patients with various liver diseases.

各種肝疾患95例における血清タイプIIIプロコラーゲンNペプチド(PIIIP)やラミニン値の変動と肝生検組織における肝線維化,細胞浸潤および巣状壊死の程度,タイプIIIコラーゲンやラミニンの分布およびその産生細胞を観察し,さらに血清PIIIP,ラミニン値が肝線維化のマーカーになり得るか否かを検討した.血清PIIIPは活動性の肝病変を呈する疾患で高値を呈し,肝細胞障害に伴なうタイプIIIコラーゲンの形成を反映するものと思われた.また,血清ラミニンは肝線維化の高度な肝疾患例で高値を呈し,基底膜形成の増加をよく反映するものと思われ,血清PIIIPとラミニンを同時に測定することは,肝疾患の活動性,線維化の形成および程度の判定に有用と思われた.また,タイプIIIコラーゲンは伊東細胞,肝細胞,内皮細胞や線維芽細胞,ラミニンは内皮細胞,伊東細胞,肝細胞および胆管上皮細胞などにより産生されることが示唆された.

Abstracts of selected papers presented at the 74th general meeting of the Japanese Society of Gastroenterology

S OF SELECTED PAPERS PRESENTED AT THE 74TH GENERAL MEETING OF THE JAPANESE SOCIETY OF GASTROENTEROLOGY March 24-26, 1988 Sendai, Japan Chairman: Toshio SATO, M.D.