Hidero Ogino

The Role of Hepatitis C Virus in Hepatocellular Carcinoma in Japan

Increasing numbers of patients with hepatocellular carcinoma (HCC) have been reported in Japan. In this paper, we investigated the role of hepatitis C virus (HCV) in HCC and the reason for the increase, using patients admitted to our university hospital from 1945 to 1992. 99 (73%) of 135 patients with HCC were positive for anti-HCV. Prospective studies demonstrated that 22 of 158 (14%) patients with chronic hepatitis C, and 31 of 70 (44%) cirrhotic patients with anti-HCV developed to HCC during the follow-up period (10.1 +/- 3.3 and 7.3 +/- 3.5 years, respectively). Prolonged survival of cirrhotic patients during past decades would also contribute to the increasing number of HCC cases as well as the number of HCV infections in Japan.

Susceptibility to primary biliary cirrhosis is associated with human leukocyte antigen DRB1*0803 in Japanese patients

An association of primary biliary cirrhosis (PBC) with human leukocyte antigen (HLA) class II has been reported in previous studies based on the results of serological HLA typing. To evaluate the association between PBC and HLA class II more precisely, we performed HLA-DRB1 and DPB1 genotyping in 53 Japanese patients with PBC using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In DRB1 genotyping, the frequency of the*0803 allele was significantly higher in patients with PBC than that in control subjects. Twenty out of 53 patients were*0803 positive (37.7%), whereas only five out of 60 controls (8.3%) had the allele (relative risk = 6.67;P < 0.001; correctedP < 0.05). In DPB1 genotyping, there was no significant difference in the frequency of the DPB1 alleles between patients with PBC and controls. Amino acid analysis of the DRβ chain revealed that the frequency of leucine at position 74 was significantly higher in patients with PBC than that in controls. These results suggest that HLA-DRB1*0803 allele and a subsequent amino acid substitution encoded by the polymorphic regions of the allele may play an important role in the pathogenesis of PBC.

Hepatitis B, C and G virus infection in patients with lymphoproliferative disorders

Abstract To define the relationship between hepatitis viruses including GBV-C/HGV and lymphoproliferative disorders, we investigated the prevalence of HBV, HCV and GBV-C/HGV infection in patients with non-Hodgkins lymphoma (NHL) and acute lymphocytic leukemia (ALL). A total of 43 subjects (26 males and 17 females, mean age 59.0 years old) consisting of 33 NHL and ten ALL patients were studied. All serum samples were tested for HBsAg, anti-HBc, HBV-DNA, anti-HCV, HCV-RNA and GBV-C/HGV-RNA. We compared these patients with two sets of control subjects. Control subjects (1) consisted of 45 age and sex matched subjects who underwent colonoscopy from July 1995 to June 1996, and control subjects (2) consisted of 10 599 subjects who received a general medical check-up in Toyama prefecture. HBsAg, anti-HBc and HBV-DNA were detected in the serum of 1/33 (3.0%), 15/33 (45.5%), and 0/33 (0%) of NHL patients, and 1/10 (10.0%), 5/10 (50.0%), and 1/10 (10.0%) of ALL patients, respectively. No significant differences were detected among each group compared with control subjects (1). Anti-HCV and HCV-RNA were detected in the serum of 4/33 (12.1%) NHL patients, but in none of the ten ALL patients. In contrast, none of the control subjects tested positive for both anti-HCV and HCV-RNA while 2/45 (4.4%) were positive for anti-HCV. Thus, the positive rate of HCV-RNA in NHL patients showed a tendency to be high compared with control subjects (1). GBV-C/HGV-RNA was not detected in the serum of lymphoproliferative disorders patients or control subjects (1). In NHL patients, the positive rate of anti-HCV was significantly higher than that of control subjects (2) ( P

Effects of chenodeoxycholic and ursodeoxycholic acids on interferon-γ production by peripheral blood mononuclear cells from patients with primary biliary cirrhosis

Ursodeoxycholic acid (UDCA) administration can obtain marked improvement of primary biliary cirrhosis (PBC). Recently, UDCA has been demonstrated to have a direct effect on immunological reactions in patients with PBC in that the aberrant expression of major histocompatibility complex (MHC) class I molecules was markedly reduced after UDCA treatment. To understand the immunological effect of UDCA, we analyzed interferon (IFN)-γ production in peripheral blood mononuclear cells (PBMCs) from 29 patients with PBC treated with UDCA (group 1), 19 patients with PBC who were not treated with UDCA (group 2), 11 healthy subjects (group 3), and 12 patients with chronic viral hepatitis (group 4). IFN-γ production was investigated because the excess production of this cytokine is associated with the aberrant expression of MHC molecules. Whereas IFN-γ production in the patients in group 2 was significantly increased, the level of production in group 1 was similar to that in the control groups (groups 3 and 4). There was significant improvement in IFN-γ production in 6 patients with PBC after UDCA treatment. The effect of UDCA and chenodeoxycholic acid (CDCA) on IFN-γ production in PBMCs from 12 normal subjects was also analyzed. IFN-γ was produced dose-dependently according to concentrations of CDCA ranging from 0.1 to 10 μM, but the increase in production was markedly suppressed by the addition of UDCA. We conclude that low doses of CDCA enhance IFN-γ production and may therefore lead to the aberrant hepatic expression of MHC molecules, and that the increase in IFN-γ production is suppressed by UDCA.

A Case of Acute Gastric Anisakiasis Presenting with Malignant Tumor-like Features: A Large Gastric Vanishing Tumor Accompanied by Local Lymph Node Swelling

Here we present a case of acute gastric anisakiasis with rare manifestations such as vanishing gastric tumor and accompanying local lymph node swelling. This report offers some important clues for considering the immunopathological features of gastric infection by Anisakis.

Three cases of primary biliary cirrhosis associated with bronchial asthma

The association of primary biliary cirrhosis (PBC) and bronchial asthma was observed in three patients. All of these patients were female (53, 54, and 41 years old, respectively), and were positive for antimitochondrial antibodies. The patients fulfilled the diagnostic criteria of both PBC and bronchial asthma. Bronchial asthma preceded PBC in two patients, and the reverse order was seen in the other. Patient the clinical symptoms were mainly due to the bronchial asthma. Two patients had asymptomatic PBC and the third patient complained of pruritus. The liver histology showed mild to moderate eosinophilic infiltration in addition to the ductal and hepatic parenchymal changes characteristic of PBC. A survey of 266 cases of PBC referred to us disclosed that, in 6 of these, the PBC was associated with bronchial asthma, while no association with bronchial asthma was the material of found in 166 patients with viral hepatitis in our liver biopsy files. The 3 present cases we experienced suggest that bronchial asthma may be included in the list of extrahepatic diseases associated with PBC. The significance of this association is unclear and may merit further study. Steroid therapy, which is known to cause adverse effects in PBC, was employed for bronchial asthma in these 3 patients. Another therapeutic approach will have to be considered in patients with bronchial asthma associated with PBC.

Reduced expression of cellularfos gene in peripheral blood mononuclear cells of patients with primary biliary cirrhosis

Abstract Abnormal expression of certain cellular oncogenes in peripheral blood mononuclear cells (PBMC) is associated with several autoimmune disorders and is thought to reflect a pathologically activated state in various lymphocytic subpopulations. Using the Northern blot hybridization technique, we studied the expression of cellular (c-) fos , c- myc and N- ras genes in PBMC isolated from patients with primary biliary cirrhosis (PBC) and normal control subjects. The expression of c- fos gene was reduced significantly in patients with PBC, while there was no significant difference between the two groups in the expression of c- myc and N- ras genes. Stimulation of PBMC with mitogens in vitro increased c- fos gene expression markedly to a similar extent in both normal subjects and in patients with PBC. Furthermore, the reduced expression of c- fos gene recovered significantly in all the patients examined after treatment with ursodeoxycholic acid (UDCA). These results suggest that the reduced expression of c- fos gene in PBMC is a reversible functional manifestation of PBC and that UDCA therapy for PBC may improve abnormal lymphocyte function.

An autopsy case of severe herpes hepatitis after bone marrow transplantation.

症例は45歳の男性. 1995年2月1日に慢性骨髄性白血病に対して同種骨髄移植を行い, 急性移植片対宿主病合併のため免疫抑制療法を受けていた. 症状は軽快し, 一時退院となったが, 6月22日 (移植後141日目) 肺炎を発症し再入院となった. 7月30日より前額部に水疱性皮疹 (皮膚生検で単純ヘルペス感染 (HSV) と診断) が出現した. このときALT2394IU/l, AST21031U/lとトランスアミナーゼの急上昇を示す肝障害を認め, 血小板数2.4万/μl, FDP61.3μg/dlとDICの合併も認めた. 8月5日, 肺炎の増悪による呼吸不全により死亡した. 剖検では, 肝小葉中心性に出血性凝固壊死を認め, HSV-2のポリクローナル抗体を用いた免疫染色からもHSV-2感染による肝障害と推察された. 免疫能の低下した宿主においては, HSV感染により重症肝炎を呈する場合があり留意すべきと考えられた.

Clearance of hepatitis B surface antigen after allogeneic bone marrow transplantation from hepatitis B virus immune donor.

症例は34歳, 男性. 平成7年6月白血球増多症の精査のため当科初診. WBC 2, 3500/μl, Ph1染色体陽性であり慢性骨髄性白血病 (CML) と診断, 同年11月1日HLAの一致した38歳の姉より同種骨髄移植を施行した. 移植前の血液検査では, 患者はHBs抗原陽性, HBe抗体陽性, DNAポリメラーゼ陰性のHBVキャリアーで, ドナーはHBs抗体陽性, HBc抗体陽性でありHBVに対する免疫が成立していると考えられた. 移植後, ALTは36日目に134IU/lまで上昇し, 41日目にHBs抗原陰性, HBs抗体陽性となり以後ALTは一旦正常化した. その後移植片対宿主病の合併を認めたがCMLの再発はみられず平成9年3月までの15カ月間HBs抗原陰性, HBs抗体陽性の状態は持続した. 本症例ではドナーのHBVに対する免疫移行によりレシピエントにメジャーセロコンバージョンが起こったものと考えられた.

A case report of the vertical infection from HBsAg-negative mother.

症例は26歳, 女性. 平成6年8月に第1子を妊娠. HBVスクリーニングではRPHA法にてHBs抗原陰性であった. 平成7年3月に第1子を出産. 平成8年1月, 母親に食欲低下が出現. AST 1, 573IU/l, ALT 2, 092IU/lと肝障害を指摘され入院となった. 入院時のウイルスマーカーはHBs抗原 (EIA法) 陽性, HBe抗原 (EIA法) 陰性, HBe抗体 (EIA法) 陽性. HBc抗体 (PHA法) は224と高値であり, HBV関連ポリメラーゼ活性 (RA法) は202cpmとHBVキャリアー状態であった. HBs抗原は4カ月間持続陽性であった. 第1子のHBVマーカーを調べたところHBs抗原 (EIA法) 陽性, HBe抗原 (EIA法) 陽性, HBe抗体 (EIA法) 陰性とキャリアー状態であった. HBs抗原陰性のキャリアーの存在が知られており, HBV母子感染防止事業においても輸血事業と同様にHBs抗原, HBc抗体測定の併用が必要と考え報告した.