Hepatitis: Abe M

Abe M, Akbar SM, Onji M. · Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan. · Hepatol Res. · Pubmed #16890177 No free full text.

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Neuman MG, Brenner DA, Rehermann B, Taieb J, Chollet-Martin S, Cohard M, Garaud JJ, Poynard T, Katz GG, Cameron RG, Shear NH, Gao B, Takamatsu M, Yamauchi M, Ohata M, Saito S, Maeyama S, Uchikoshi T, Toda G, Kumagi T, Akbar SM, Abe M, Michitaka K, Horiike N, Onji M. · Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Ontario, Canada. · Alcohol Clin Exp Res. · Pubmed #11391079 No free full text.

Abstract: This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Manuela G. Neuman. The presentations were (1) New aspects of hepatic fibrosis, by D. A. Brenner; (2) Cellular immune response in hepatitis C models, by B. Rehermann; (3) The role of interleukin-10 in acute alcoholic hepatitis, by J. Taieb, S. Chollet-Martin, M. Cohard, J. J. Garaud, and T. Poynard; (4) Cytokine-mediated apoptosis in vitro, by M. G. Neuman; (5) Signaling for apoptosis and repair in vitro, by G. G. Katz, R. G. Cameron, N. H. Shear, and M. G. Neuman; (6) Interferons activate the P42/44 mitogen-activated protein kinase and Janus Kinase signal transducers and activation of transcription (JAK-STAT) signaling pathways in hepatocytes: Differential regulation by acute ethanol via a protein kinase C-dependent mechanism, by B. Gao; (7) Genetic polymorphisms of interleukin-1 in association with the development of Japanese alcoholic liver disease, by M. Takamatsu, M. Yamauchi, M. Ohata, S. Saito, S. Maeyama, T. Uchikoshi, and G. Toda; and (8) Increased levels of macrophage migration inhibitory factor in sera from patients with alcoholic liver diseases, by T. Kumagi, S. M. F. Akbar, M. Abe, K. Michitaka, N. Horiike, and M. Onji.

Horiike N, Fazle Akbar SM, Michitaka K, Joukou K, Yamamoto K, Kojima N, Hiasa Y, Abe M, Onji M. · Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-Cho, Ehime 791 0295, Japan. · J Clin Virol. · Pubmed #15653419 No free full text.

Abstract: BACKGROUND: Both the hepatitis B virus (HBV) and the immune response of the hosts to HBV play important roles in the pathogenesis of chronic hepatitis B (CHB). Lamivudine is a potent antiviral agent with minimal immune modulator capacity. Moreover, lamivudine causes severe side effects like breakthrough of HBV DNA and breakthrough hepatitis in patients with CHB. On the other hand, vaccine therapy, a recently-developed immune therapy, exhibits potent immune modulatory potentials and almost no side effects, but possesses little antiviral capacity in patients with CHB. OBJECTIVES: The aim of this clinical trial is to evaluate the efficacy of a combination therapy of lamivudine and vaccine in patients with CHB. STUDY DESIGN: Seventy-two patients with CHB (hepatitis B e antigen (HBeAg)-positive, 40; antibody to HBeAg (anti-HBe)-positive, 32). All patients received lamivudine at a dose of 100 mg daily for 12 months. Fifteen patients (HBeAg+, 9; anti-HBe+, 6) receiving oral lamivudine were also given a vaccine containing 20 microg of hepatitis B surface antigen, intradermally, once every 2 weeks for 12 times (combination therapy). RESULTS: Twelve months after the start of therapy, serum HBV DNA became negative in 9 of 9 (100%) HBeAg+ CHB patients receiving combination therapy and in 15 of 31 (48%) HBeAg+ CHB patients receiving lamivudine monotherapy (P < 0.05). The rate of seroconversion from HBeAg to anti-HBe was also significantly higher in patients receiving combination therapy (56% versus lamivudine monotherapy, 16%, P < 0.05). Of the 57 patients receiving lamivudine monotherapy, breakthrough of HBV DNA was found in 10 and breakthrough hepatitis was found in 4; however, these were not seen in any patient receiving combination therapy. CONCLUSIONS: Combination therapy represents a better therapeutic regimen with few complications in patients with CHB.

Yoshida O, Abe M, Furukawa S, Murata Y, Hamada M, Hiasa Y, Matsuura B, Akbar F, Michitaka K, Onji M. · Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on. · Intern Med. · Pubmed #19252353 links to  free full text

Abstract: Autoimmune hepatitis is a chronic liver disease, and both genetic background and environmental factors are related to its pathogenesis. Here, we report that out of five members of a family with similar human leukocyte antigen haplotypes, two developed autoimmune hepatitis, one was positive for antinuclear antibody, and the remaining two had no features of autoimmunity. The two patients with autoimmune hepatitis had a history of medication use, whereas the other family members did not. Our familial study suggests that in addition to genetic background, medication use and other environmental factors may be related to the onset of autoimmune hepatitis.

Yamamoto T, Kondo S, Sugawara A, Yonechi M, Nishioka K, Meguro T, Abe M, Murakami K, Inoue J, Ueno Y, Shimosegawa T. · Department of Gastroenterology, Tohoku Kosei-Nenkin Hospital. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19057164 No free full text.

Abstract: A 82-year-old asymptomatic HBV carrier man was admitted with liver dysfunction in May 2007. With anti-HBe antibody and high viral load, he had fulminant hepatic failure without proximate cause. He was treated with entecavir and corticosteroids, but died about one month later. Autopsy specimen of liver revealed submassive hepatic necrosis with faint regeneration. HBV obtained was segregated into genotype Bj, and mutation was detected at nt1896 in a precore region.

Michitaka K, Tokumoto Y, Uesugi K, Kisaka Y, Hirooka M, Konishi I, Mashiba T, Abe M, Hiasa Y, Matsuura B, Horiike N, Shoda T, Onji M. · Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. · Hepatol Res. · Pubmed #19000057 No free full text.

Abstract: Aim: The aim of this study is to clarify the cerebral functions in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). Methods: We studied 58 patients with CH (20 in fibrosis stage F1, 20 in F2, 18 in F3), 77 with LC (46 rated as Child-Pugh class A, 24 as B, 7 as C), and 20 healthy volunteers (HV). Computer-aided quantitative neuropsychiatric function test systems, including eight neuropsychiatric tests were performed. Results: Subjects with results over the cut-off value for healthy subjects ranged from 11.1-28.6% in CH and 19.5-36.4% in LC. The percentages with abnormality in at least one test in CH and LC were 72.4% and 80.6%, respectively, which were significantly higher than that in the HV group (35.0%) (P = 0.003, P = 0.0003, respectively). Among CH subjects, those with three or more abnormal results in the F1, F2 and F3 subgroups were 15.0%, 20.0% and 38.9%, respectively. Among LC subjects, those with three or more abnormal results in the Child-Pugh class A, B and C subgroups comprised 30.4%, 50.0% and 57.1%, respectively. The rate in the CH F3 subgroup (P = 0.011) and in all three LC subgroups (P = 0.023, P = 0.001, P = 0.002, respectively) were significantly higher than that in the HV group. Conclusion: The percentage of patients with neuropsychiatric function impairment was high in both LC and CH, especially in stage F3. Neuropsychiatric dysfunction may initiate in CH in a considerable number of patients.

Abe M. · Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. · Hepatol Res. · Pubmed #18705762 No free full text.

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Yoshida O, Akbar F, Miyake T, Abe M, Matsuura B, Hiasa Y, Onji M. · Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. · Clin Exp Immunol. · Pubmed #18307521 links to  free full text

Abstract: The primary aim of this study was to evaluate the role of natural killer (NK) cells on antigen-specific adaptive immune responses. After analysing the mechanism of impaired adaptive immune responses of NK-depleted mice, an immune interventional approach was developed to restore adaptive immunity in NK-depleted mice. NK cells were depleted from mice by administration of anti-asialo GM1 antibody (100 mul/mouse), twice, at an interval of 48 h. Hepatitis B surface antigen (HBsAg) was administered intraperitoneally to normal C57BL/6 mice (control mice) and NK-depleted mice. The levels of antibody to HBsAg (anti-HBs) in the sera and HBsAg-specific lymphocytes in the spleen were assessed. The functions of T lymphocytes, B lymphocytes and dendritic cells (DCs) were evaluated in vitro. HBsAg-pulsed DCs were prepared by culturing spleen DCs with HBsAg for 48 h and administered once to NK-depleted mice. The levels of anti-HBs in the sera and HBsAg-specific lymphocytes were significantly lower in NK-depleted mice compared with control mice (P < 0.05). The functions of T and B lymphocytes were similar between control mice and NK-depleted mice. However, the functions of spleen DC and liver DC were significantly lower in NK-depleted mice compared with control mice (P < 0.05). Administration of HBsAg-pulsed DCs, but not HBsAg, induced HBsAg-specific humoral and cellular immune responses in NK-depleted mice. Our study suggests that cross-talk between NK cells and DCs regulates the magnitude of adaptive immunity. In addition, antigen-pulsed immunogenic DCs represent potent immune modulator even if subjects with diminished innate immunity.

Akbar F, Yoshida O, Abe M, Hiasa Y, Onji M. · Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. · Hepatol Res. · Pubmed #17931186 No free full text.

Abstract: Approximately 350-400 million people worldwide are chronically infected with the hepatitis B virus (HBV). These individuals harbor the virus for their whole life and they transmit the virus to uninfected individuals. In addition, considerable numbers of chronic HBV carriers develop progressive liver diseases like chronic hepatitis B, liver cirrhosis and hepatocellular carcinoma. At present, antiviral agents like type-1 interferons, lamivudine, adefovir and entacavir are used to treat a selected population of chronic HBV carriers. These antiviral treatments are not satisfactory in that they are unable to eradicate HBV, only partially efficient in less than 30% subjects, expensive, can have debilitating side-effects and require constant monitoring. In addition, once treatment is stopped, the virus and clinical conditions return in many patients. Recent advancements in cellular and molecular biology indicate that the host's immune responses to HBV play cardinal roles during acquisition, pathogenesis, progression, and complications of chronic HBV infection. Immune responses are also important in the context of antiviraltherapy and clinical recovery. This explains why the efficacy of antiviral drugs is limited even in some selected patients with chronic HBV infection. Various published work now state that HBV-specific immunity may be beneficial for patients with chronic HBV infection and non-HBV-specific immunity may be related to flare up of liver diseases. Accordingly, a new few field of immunological research and clinical application of prophylactic vaccines (vaccine therapy) has been started in chronic HBV carriers. Vaccine therapy has inspired optimism as a new therapeutic approach, but it is unlikely that the present regimen of vaccine therapy will stand the test of time. Based on present understandings about vaccine/host interactions, we provide herein an outline for engineering more potent regimen of HBV-specific immune therapy against HBV.

Abe M, Kaizu K, Matsumoto K. · Department of Medicine, Division of Nephrology and Endocrinology, Nihon University, School of Medicine, Tokyo, Japan. · Ther Apher Dial. · Pubmed #17498008 No free full text.

Abstract: A 60-year-old male with cerebral infarction was admitted to our hospital and treated with edaravone. On day 12 of hospitalization, he suddenly lost consciousness and went into shock. Based on the laboratory findings, acute renal failure (ARF), fulminant hepatitis, and disseminated intravascular coagulation (DIC) were diagnosed. We immediately initiated continuous hemodiafiltration for three days and performed three sessions of plasma exchange. Following this, a gradual improvement was observed in the patient's general condition and laboratory values. On day 17 of hospitalization, intermittent hemodialysis (HD) was initiated. On day 20 of hospitalization, his renal function started to improve with an increase in urine volume. HD was successfully discontinued on the same day. Although the drug lymphocyte stimulation test for edaravone was negative, edaravone-induced fulminant hepatitis was suggested based on liver biopsy findings. We present a case of ARF, fulminant hepatitis, and DIC due to edaravone administration that was successfully treated with blood purification techniques. Since the use of edaravone treatment is expected to increase in the future, it is essential that clinicians consider the potential adverse effects of this treatment. It is suggested that blood purification is effective in inducing remission in patients with complications due to edaravone treatment.

Yao H, Michitaka K, Tokumoto Y, Murata Y, Mashiba T, Abe M, Hiasa Y, Horiike N, Onji M. · Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime-ken, 791-0295, Japan. · World J Gastroenterol. · Pubmed #17461459 links to  free full text

Abstract: It is controversial whether steroid therapy should be continued to prevent the recurrence of autoimmune hepatitis (AIH) in patients who have undergone liver transplantation (LTx) due to AIH. We report a case of recurrent autoimmune hepatitis after LTx despite a persistently normal range of alanine aminotransferase (ALT). A 50-year-old woman was admitted to our hospital because of jaundice and severe liver dysfunction, where she was diagnosed with liver failure due to AIH. Steroid therapy was not effective enough and the patient received living-donor LTx in 1999. Following the operation, the level of ALT was maintained within a normal range and anti-nuclear antibody (ANA) became negative, however, the serum level of IgG gradually elevated and ANA became positive, while platelets decreased. A liver biopsy performed 6 years after LTx showed histological findings of AIH and she was diagnosed with recurrent AIH. A recurrence of AIH may occur after LTx even if the level of ALT remains within a normal range. We consider that a protocol liver biopsy should be performed in patients who undergo LTx due to AIH to decide the indication for steroid therapy.

Kuwahara R, Saitsu H, Abe M, Takata A, Tanaka K, Hino T, Ide T, Kuromatsu R, Tanikawa K, Kage M, Kumashiro R, Sata M. · The Second Department of Medicine, Kurume University School of Medicine and the Center of the 21st Century Center of Excellence Program for Medical Science, 67 Asahi-Machi, Kurume, Fukuoka 830-0011, Japan. · Dig Dis Sci. · Pubmed #17342404 No free full text.

This publication has no abstract.

Niiya T, Akbar SM, Yoshida O, Miyake T, Matsuura B, Murakami H, Abe M, Hiasa Y, Onji M. · Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan 791-0295. · J Nutr. · Pubmed #17311958 links to  free full text

Abstract: We examined whether antigen-specific immune responses are lower in mice with protein energy malnutrition (PEM mice) compared with nourished (control) mice. The mechanisms underlying reduced antigen-specific immune responses of PEM mice were evaluated through analysis of the functional capacities of antigen-presenting dendritic cells (DC). PEM mice were produced by subjecting male C57BL/6 mice for 52 wk to a daily food intake equivalent to 70% of the mean amount consumed by the control mice that consumed food ad libitum. PEM mice and control mice were immunized with hepatitis B vaccine containing hepatitis B surface antigen (HBsAg) at 52 wk and humoral and cellular immune responses to HBsAg were evaluated at 58 wk. Lymphoproliferative assays were performed to assess the functional capacities of lymphocytes and DC. After 52 wk of food restriction, PEM mice had a 49% lower body weight than controls, almost no subcutaneous fat, severe muscle wasting, and atrophied spleen. All control mice developed antibodies to HBsAg (anti-HBs) in the sera and HBsAg-specific lymphocytes in the spleen as a result of immunization with the hepatitis B vaccine. PEM mice, however, were almost unresponsive to immunization with the hepatitis B vaccine. In PEM mice, the numbers of spleen DC, the T lymphocyte stimulatory capacities of DC, and their production of IL-12p70 and IFN-gamma was less than those of control mice (P < 0.05). We suggest that chronic undernutrition disrupts antigen-specific immune responses and that this disruption can be attributed at least in part to reduced frequencies and impaired functions of DC.

Abe M, Onji M, Kawai-Ninomiya K, Michitaka K, Matsuura B, Hiasa Y, Horiike N. · Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. · Clin Gastroenterol Hepatol. · Pubmed #17218164 No free full text.

Abstract: BACKGROUND & AIMS: Acute onset autoimmune hepatitis (acute AIH) is difficult to diagnose by using serologic data. In addition, some patients with the severe form of acute AIH do not respond to immunosuppressive therapy and have a poor outcome. In this study, we analyzed the clinicopathologic features of patients who were diagnosed as having acute AIH. METHODS: Retrospective review of patients with presumed acute AIH at Ehime University Graduate School of Medicine was performed. RESULTS: In liver tissue, infiltrates in the portal area and plasma cell infiltration are more common in acute AIH compared with acute hepatitis caused by other causes. Patients with acute AIH who did not have severe jaundice at the time of diagnosis exhibited a very good response to corticosteroid therapy, despite lower titers of antinuclear antibody (ANA). Most patients with acute AIH with higher levels of bilirubin and titers of ANA in sera respond poorly to corticosteroid therapy. CONCLUSIONS: Histologic findings might be useful for the early diagnosis of acute AIH. Acute AIH patients with high levels of bilirubin and high titers of ANA in sera often do not respond to corticosteroid therapy.

Miyake T, Miyaoka H, Abe M, Furukawa S, Shigematsu S, Furukawa E, Ikeda R, Okita S, Okada T, Yoshida O, Murata Y, Akbar SM, Matsuura B, Michitaka K, Horiike N, Hiasa Y, Onji M. · Department of Internal Medicine, Hospital of Saiseikai, Matsuyama, 880-2 Yamanishi-cho, Matsuyama, Ehime 791-8026, Japan. · Hepatol Res. · Pubmed #16872893 No free full text.

Abstract: BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually develops in middle-aged women. However, due to the increasing aging of the population and better diagnostic facilities, AIH is now diagnosed in older patients as well. This analysis compared the clinical and pathologic characteristics of older and middle-aged patients with AIH. PATIENTS AND METHODS: Thirteen older patients with AIH (mean age, 75.0+/-5.3 years; range, 70-89 years) and 27 middle-aged patients (mean age, 51.3+/-5.8 years; range, 41-60 years) were included in this study. In addition, the use of different treatment regimens, including prednisolone therapy and ursodeoxycholic acid (UDCA), was examined. RESULTS: There were no significant differences in gender, complications of other autoimmune diseases, and liver function tests between groups. However, the degree of hepatic fibrosis was significantly higher in older patients compared with middle-aged patients (P<0.05). Four patients with AIH in the older age group were successfully managed by UDCA alone. CONCLUSION: This study shows that older patients with abnormal liver function should be checked for AIH. In addition, UDCA may be an effective drug for management of older patients with AIH.

Horiike N, Abe M, Kumagi T, Hiasa Y, Akbar SM, Michitaka K, Onji M. · Third Department of Internal Medicine, Ehime University School of Medicine, Ehime 791-0295, Japan. · Clin Biochem. · Pubmed #15885232 No free full text.

Abstract: OBJECTIVE: We quantified cytochrome P-450 (CYP) 3A4 mRNA in the blood and liver of patients with viral liver diseases to determine whether CYP 3A4 expression is related to disease progression. DESIGN AND METHODS: Total RNA was extracted from 10 mL of blood from 12 normal volunteers, from 6 patients with acute hepatitis, 17 with chronic hepatitis, 12 with liver cirrhosis, and 16 with hepatocellular carcinoma. Total RNA from 1 mg of liver tissue was extracted simultaneously in 10 patients. CYP 3A4 mRNA was quantified by competitive reverse-transcription polymerase chain reaction and expressed as log copies/microliter. RESULTS: The CYP 3A4 mRNA titer in blood correlated with that of the liver (r = 0.65, P < 0.05). The CYP 3A4 mRNA titer was 1.6 +/- 0.4 in normal controls, 1.0 +/- 0.5 in acute hepatitis, 0.7 +/- 0.2 in chronic hepatitis, 0.5 +/- 0.2 in liver cirrhosis, 0.5 +/- 0.2 in hepatocellular carcinoma, and decreased with progression of liver disease (P < 0.05). CONCLUSION: These data suggest that the CYP 3A4 mRNA level in blood relates to progression of liver disease.

Sonoda H, Abe M, Sugimoto T, Sato Y, Bando M, Fukui E, Mizuo H, Takahashi M, Nishizawa T, Okamoto H. · Nishiarita Kyoritsu Hospital, Saga-Ken, Japan. · J Clin Microbiol. · Pubmed #15528746 links to  free full text

Abstract: Zoonotic transmission of hepatitis E virus (HEV) from captured wild deer or boars to humans has been suggested. Antibody to HEV was detected in 9% of 35 wild boars and 2% of 117 wild deer tested, and a presumably indigenous HEV of genotype 3 was isolated from a boar in Japan.

Tokumoto Y, Horiike N, Onji M, Ueda T, Kumagi T, Abe M, Michitaka K. · Third Department of Medicine, Endoscopy Center, Ehime University School of Medicine, Ehime. · Intern Med. · Pubmed #14686750 links to  free full text

Abstract: A 27-year-old Japanese man with no past history of liver disease was admitted to our hospital due to liver abnormalities. The patient was diagnosed with drug-induced hepatitis, as the three episodes of hepatitis occurred just after repeated use of hair dye. After cessation of the hair dye use, abnormal liver function tests improved to within the normal range. Although hair dyes contain various hepatotoxic compounds, hair dye is not known to cause drug-induced hepatitis. Thus, in cases of liver abnormality of unknown origin, the history of hair dye use should be investigated.

Abe M, Akbar F, Hasebe A, Horiike N, Onji M. · Third Department of Internal Medicine, Ehime University School of Medicine, 791-0295, Ehime, Shigenobu-cho, Japan. · J Gastroenterol. · Pubmed #14614603 No free full text.

Abstract: BACKGROUND: Glycyrrhizin (GL), an aqueous extract of licorice root, is known to have various immune-modulating and biological response-modifier activities. GL is used in patients with hepatitis to reduce the activity of liver inflammation; however, the mechanism underlying the anti-inflammatory activity of GL is poorly understood. As antigen-presenting dendritic cells (DC) in the tissue play a major role in the regulation of the inflammatory mucosal milieu during tissue inflammation, we studied whether the function of liver DC was altered by GL therapy in a murine model of concanavalin-A (con A)-induced hepatitis. METHODS: Liver DC were propagated from control mice or mice with Con-A-induced hepatitis, and the effect of GL on liver DC was evaluated in vivo and in vitro. RESULTS: The levels of interleukin (IL)-10 produced by liver DC were significantly lower in mice with Con-A-induced hepatitis compared with control mice. However, treatment with GL caused increased production of IL-10 in mice with Con A-induced hepatitis. The increased production of IL-10 by mice with Con A-induced hepatitis was also confirmed in vitro by culturing liver DC with GL. CONCLUSIONS: This study indicates that increased production of IL-10 by liver DC due to GL administration may be involved in downregulation of the levels of liver inflammation in mice with Con A-induced hepatitis.Glycyrrhizin (GL), an aqueous extract of licorice root, is known to have various immune-modulating and biological response-modifier activities. GL is used in patients with hepatitis to reduce the activity of liver inflammation; however, the mechanism underlying the anti-inflammatory activity of GL is poorly understood. As antigen-presenting dendritic cells (DC) in the tissue play a major role in the regulation of the inflammatory mucosal milieu during tissue inflammation, we studied whether the function of liver DC was altered by GL therapy in a murine model of concanavalin-A (Con A)-induced hepatitis.

Arima S, Michitaka K, Horiike N, Kawai K, Matsubara H, Nakanishi S, Abe M, Hasebe A, Tokumoto Y, Yamamoto K, Onji M. · Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. · J Gastroenterol. · Pubmed #14505132 No free full text.

Abstract: BACKGROUND: Many years have passed since various prophylactic policies for preventing hepatitis B virus (HBV) transmission were begun. We studied the chronological alterations in HBV infectious routes in patients with acute hepatitis B in the past 27 years. METHODS: Seventy-two patients with acute HBV infection who were admitted to our hospital during the period 1976 to 2002 were enrolled in this study. This study was divided into two periods (first period, 1976-1990; and second period, 1991-2002), and the HBV infectious routes were studied. RESULTS: Infectious routes have been changing. Posttransfusion hepatitis was seen only in the first period. In the second period, sexual transmission was the major infectious route (68%), followed by infection at a medical facility or occupational exposure such as needlestick injury (8%). CONCLUSIONS: Transmission from sexual contact has become the main infectious route of HBV in Japan.

Matsuoka S, Tsurui H, Abe M, Terashima K, Nakamura K, Hamano Y, Ohtsuji M, Honma N, Serizawa I, Ishii Y, Takiguchi M, Hirose S, Shirai T. · Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. · J Exp Med. · Pubmed #12885869 links to  free full text

Abstract: We earlier found that a rat monoclonal antibody (mAb) RE2 can induce rapid death of murine activated, but not resting, lymphocytes and lymphocyte cell lines, in a complement-independent manner, a cell death differing from typical apoptosis or necrosis. We here found that this cell death is independent of pathways involving Fas, caspase, and phosphoinositide-3 kinase. With the advantage of producing human B cell line transfectants with stable expression of human/mouse xeno-chimeric MHC class I genes, we found that RE2 epitope resides on the murine class I alpha2 domain. However, the alpha3 domain plays a key role in transducing the death signal, which mediates extensive aggregation of the MHC class I-integrin-actin filament system, giving rise to membrane blebs and pores. In mouse models with T/NKT cell activation-associated fulminant hepatitis, administration of mAb RE2 almost completely inhibited the development of liver cell injuries. Taken collectively, this form of cell death may be involved in homeostatic immune regulation, and induction of this form of cell death using the mAbs may be potentially therapeutic for subjects with immunological diseases mediated by activated lymphocytes.

Cui B, Abe M, Hidata S, Nakanishi S, Matsuura B, Michitaka K, Yamamoto K, Horiike N, Onji M. · Third Department of Internal Medicine, Ehime University School of Medicine, Ehime. · Intern Med. · Pubmed #12729321 links to  free full text

Abstract: A 31-year-old woman with Graves' disease with a 12-month-history of propylthiouracil intake and autoantibodies in the sera was admitted to our hospital. The differential diagnosis between autoimmune hepatitis and propylthiouracil-induced hepatitis was intractable. Steroid therapy was started and she showed a complete response to the treatment. Liver biopsy demonstrated acute hepatitis and plasma cell infiltration. A second liver biopsy, which was performed 10 months after starting steroid therapy, showed some inflammatory cells in the portal tracts. These findings suggest that she had been suffering from autoimmune hepatitis.

Kawai K, Michitaka K, Miyauchi S, Sano M, Abe M, Ninomiya T, Matsuura B, Masumoto T, Akbar SM, Horiike N, Onji M. · Third Department of Internal Medicine, Ehime University School of Medicine, Onsen-gun. · Intern Med. · Pubmed #12647695 links to  free full text

Abstract: A 50-year-old woman was diagnosed with acute-onset autoimmune hepatitis. She did not respond to steroid therapy including pulse therapy, and was subsequently treated with living donor-liver transplantation 36 days after the beginning of steroid therapy. Except for a period of transient mild acute rejection, her liver function tests remained within a normal range for 2.5 years after the operation. The courses of autoimmune hepatitis patients treated with living-donor liver transplantation have not been previously documented to our knowledge. Living donor-liver transplantation is thought to be one of the therapy options for severe autoimmune hepatitis.

Abe M, Furukawa S, Takayama S, Michitaka K, Minami H, Yamamoto K, Horiike N, Onji M. · Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-cho, Ehime 791-0295. · Intern Med. · Pubmed #12583618 links to  free full text

Abstract: A 25-year-old woman with no history of liver disease developed liver dysfunction associated with severe jaundice and general malaise following a prolonged therapy with minocycline for acne vulgaris. Serum anti-nuclear antibody was detected and immunoglobulin G level was elevated. Symptoms resolved and liver function normalized following minocycline discontinuation and corticosteroid administration. Our diagnosis was drug-induced hepatitis with autoimmune features, as liver histology revealed acute hepatitis. Drug-induced hepatitis should be considered when liver dysfunction or systemic symptoms develops during long-term minocycline therapy.

Yamamoto K, Terada R, Okamoto R, Hiasa Y, Abe M, Onji M, Tsuji T. · Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. · J Gastroenterol. · Pubmed #12560922 No free full text.

Abstract: BACKGROUND: Although primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) are two independent autoimmune liver diseases, it is sometimes difficult to characterize the variant forms of autoimmune liver disease. A PBC scoring system, in combination with the AIH scoring system may be helpful to characterize such patients. METHODS: A PBC scoring system was introduced that selected 14 categories characteristic of PBC. One hundred and thirty-four patients with PBC, 31 patients with autoimmune cholangitis (AIC), 22 patients with overlap syndrome, and 48 patients with AIH were included in the study. The AIC patients fulfilled the PBC criteria but were negative for anti-mitochondrial antibody and positive for anti-nuclear antibody. Overlap syndrome patients fulfilled both the PBC and AIH criteria. RESULTS: The total scores (means +/- SD) for the PBC, AIC, overlap syndrome, and AIH patients were 23.3 +/- 4.7, 9.3 +/- 4.4, 18.0 +/- 5.9, and 3.6 +/- 3.3, respectively. When definite and probable PBC patients were defined as those with a total score of over 17 and 9-17, respectively, all except for 1 patient could be classified as definite or probable PBC. Four of the 48 AIH patients were classified as probable PBC. PBC scores for the variant autoimmune liver diseases showed a wide deviation. Plotting both PBC and AIH scores in a rectangular coordinate enabled us to locate each patient with variant forms according to the deviation from classical PBC or AIH. CONCLUSIONS: The PBC scoring system might be useful in characterizing the features of variant forms of autoimmune liver disease.