Hepatitis: Shimoda S

Ishibashi H, Komori A, Shimoda S, Gershwin ME. · Clinical Research Center, National Hospital Organization (NHO), Nagasaki Medical Center, and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. · Semin Liver Dis. · Pubmed #17520519 No free full text.

Abstract: The principle of therapy for chronic inflammatory liver diseases is the removal of causal agents. For autoimmune liver diseases, however, total removal of causal agents and immune cells is impossible. Therefore, autoimmune liver diseases are presently treated by suppression of the immune response. Autoimmune hepatitis is characteristically responsive to corticosteroids, often used in combination with azathioprine to obtain a steroid-sparing effect. For primary biliary cirrhosis, ursodeoxycholic acid is safe and is the first choice for treatment. Treatment of this autoimmune liver disease should also address various symptoms and complications arising from any associated autoimmune diseases, particularly cholestasis and cirrhosis-related complications. For primary sclerosing cholangitis there are no established immunomodulatory therapies, but medical, endoscopic, and surgical treatments are applicable to this disease. Liver transplantation becomes indicated during the eventual end stages of each of these immune-mediated liver diseases.

Ishibashi H, Shimoda S, Nakamura M. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #16722447 No free full text.

This publication has no abstract.

Ichiki Y, Aoki CA, Bowlus CL, Shimoda S, Ishibashi H, Gershwin ME. · Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, TB192, One Shields Avenue, Davis, CA 95616, USA. · Autoimmun Rev. · Pubmed #15990080 No free full text.

Abstract: T cells play a central role in the immunopathogenesis of AIH. Until recently CD4+ T cells were thought to be critical for disease development, increasing evidence has shown that CD8+ T and gammadelta T cells also play a significant role. The predisposition of certain HLA genotypes to AIH as well as the clonal expansion of a limited number of T cell receptors suggests that the presentation of a self-antigen or a molecular mimic may be responsible for the initiation of the immune response. Given the association of AIH with viral hepatitis, it is thought that the loss of tolerance begins with an infection of hepatocytes and subsequent cytolysis by CD8+ T cells. The presentation of self-antigens or molecular mimics leads to activation and clonal expansion of T cells; this process may be increased by impaired regulatory T cells and a defect in apoptosis. Ultimately T cells initiate B cell production of autoantibodies, proinflammatory cytokines and finally hepatocyte cytotoxicity.

Ichiki Y, He XS, Shimoda S, Ishibashi H, Keeffe EB, Rossaro L, Gershwin ME. · Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, TB192, One Shields Avenue, Davis, CA 95616, USA. · Autoimmun Rev. · Pubmed #15722254 No free full text.

Abstract: T cells are involved in the pathogenesis of important liver diseases including both autoimmune liver diseases and viral hepatitis. In addition to playing a crucial role in the control of hepatitis viruses, T cell responses are also responsible for the liver injury during acute and chronic phases of viral hepatitis. In this article, we reviewed current literature on T cell immunity to hepatitis B and C viruses. In addition, antigen presenting cells that are critical for T cell immunity against these viruses are also discussed. This will provide insights to the understanding of T cell immunity in autoimmune liver diseases due to the similar role of T cells in autoimmune liver diseases and viral hepatitis.

Furusyo N, Kajiwara E, Takahashi K, Nomura H, Tanabe Y, Masumoto A, Maruyama T, Nakamuta M, Enjoji M, Azuma K, Shimono J, Sakai H, Shimoda S, Hayashi J, Anonymous00398. · Department of General Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka, Japan. · J Gastroenterol Hepatol. · Pubmed #18248381 No free full text.

Abstract: AIM: The aim of the present study was to investigate the association between the length of the treatment period and the cumulative dose of pegylated interferon alpha-2b (peg-IFN alpha-2b) plus ribavirin (RBV) and their effectiveness in the treatment of chronic hepatitis C. METHODS: Seven hundred and fifteen patients received peg-IFN alpha-2b plus RBV treatment for 48 weeks and 24 weeks for genotypes 1 (n = 586) and 2 (n = 129), respectively. RESULTS: Sustained virological responses (SVR), defined as serum hepatitis C virus (HCV)-RNA undetectable at 24 weeks after the end of treatment, were 42.4% and 74.4% in genotypes 1 and 2, respectively, on an intention-to-treat analysis. SVR significantly increased with treatment length (4.7%, 36.4%, and 51.8% for < 24 weeks, 24-47 weeks, and 48 weeks, respectively, for genotype 1; and 28.6%, 57.1%, 78.3% for < 12 weeks, 12-23 weeks, and 24 weeks, respectively, for genotype 2). SVR significantly increased with total cumulative treatment dose (21.1%, 36.5%, and 52.9% with < 60%, 60-79%, and >or= 80% in peg-IFN dose; 29.6%, 51.1%, and 59.2% with < 60%, 60-79%, and >or= 80% in RBV dose) in genotype 1, although it did not differ significantly for genotype 2. CONCLUSIONS: In peg-IFN alpha-2b plus RBV treatment for chronic hepatitis C, it is important to complete the target length of treatment and to continue the target dosage to achieve SVR, especially for genotype 1 patients.

Furusyo N, Katoh M, Tanabe Y, Kajiwara E, Maruyama T, Shimono J, Sakai H, Nakamuta M, Nomura H, Masumoto A, Shimoda S, Takahashi K, Azuma K, Hayashi J, Anonymous00124. · Department of General Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka 812-8582, Japan. · World J Gastroenterol. · Pubmed #16521196 links to  free full text

Abstract: AIM: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2, a multi-center study was retrospectively analyzed. METHODS: In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS: The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9% vs 92.9%), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8% vs 92.0%). CONCLUSION: The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16 weeks.

Tsai NC, Shimoda N, Wong L, Shimoda S, Goad K, Yee H, Chen M. · Department of Medicine, John Burns School of Medicine, University of Hawaii, USA. · Hawaii Med J. · Pubmed #10363429 No free full text.

Abstract: OBJECTIVES: Interferon alpha-2b therapy for Chronic Hepatitis C patients has been unsatisfactory. Recombinant Granulocyte Macrophage Colony-Stimulating Factor has been shown to have anti-viral effects in vivo and in vitro via cytokines release. Recently its effects on chronic hepatitis B and possibly chronic hepatitis C were reported. We, decided to conduct a pilot study to evaluate the anti-viral effects of recombinant human GM-CSF mono-therapy in patients with chronic hepatitis C and to assess its side effects. METHODS: A total of 10 patients (male/female: 5/5) (age: 34-60, mean: 45) seen in our center between 2/95 to 2/96 were randomly selected to receive recombinant human Granulocyte Macrophage Colony-Stimulating-Factor at 125 ug/m2 subcutaneously daily for two weeks followed by three times weekly for another 8 weeks. Biochemical (ALT) and viral (HCV-RNA) responses were measured prior to treatment and at weeks four and eight. Side effects were recorded. RESULTS: Six out of the ten patients treated had significant viral reduction but none became negative. Eight out the ten patients treated showed biochemical improvement and three out of the eight had normalized liver enzymes. Age, sex, stage of the disease did not influence the response but there seems to be a tendency for patients with higher pre-treatment viral level to respond virally. Side effects are minimal and well-tolerated. CONCLUSION: Recombinant human Granulocyte Macrophage Colony-Stimulating-Factor in the dose used has anti-viral effects in the majority of the chronic hepatitis C patients studied. Side effects are minimal and well tolerated. Further study with higher doses and longer duration is needed to prove its clinical efficacy in treating patients with chronic hepatitis C.

Takii Y, Abiru S, Fujioka H, Nakamura M, Komori A, Ito M, Taniguchi K, Daikoku M, Meda Y, Ohata K, Yano K, Shimoda S, Yatsuhashi H, Ishibashi H, Migita K. · Clinical Research Center, NHO Nagasaki Medical Center, Omura, Nagasaki, Japan. · Liver Int. · Pubmed #17696939 No free full text.

Abstract: BACKGROUND/AIMS: The objective of this study was to evaluate the expression of microsomal prostaglandin E synthase-1 (mPGES-1) in hepatocellular carcinoma (HCC) tissues. METHODS: Forty surgically resected HCC tissues with adjacent non-tumorous liver tissues and 14 surgically resected, histologically normal liver tissues were used. The immunohistochemical expressions of the mPGES-1 protein in these HCC tissues and normal control livers were analysed. mPGES-1 mRNA expression was also analysed by the real-time polymerase chain reaction method using the same tissues. RESULTS: Microsomal prostaglandin E synthase-1 was not expressed in hepatocytes but instead in vascular endothelial cells and bile duct epithelial cells in normal liver tissues. The mPGES-1 expression in HCC tissues was significantly greater than its expression in the non-tumorous tissues. All types of HCC expressed more mPGES-1 than normal or hepatitis livers, and the levels of mPGES-1 expression in poorly differentiated HCC were similar to the levels in well-differentiated HCC. The mPGES-1 mRNA expression paralleled its protein expression in these tumorous and non-tumorous tissues. CONCLUSIONS: The present study is the first to demonstrate a high expression of mPGES-1 in well-differentiated HCC as well as in poorly differentiated HCC. These findings suggest that mPGES-1 may play a role in the advanced as well as early stage of hepatocarcinogenesis.

Kawano A, Namitome R, Matsunaga T, Maruyama T, Yamamoto I, Shimoda S. · Department of Internal Medicine, Kitakyushu Municipal Medical Center. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #17611384 No free full text.

Abstract: We reported a case of advanced malignant melanoma with multiple metastases to the liver and the gastrointestinal tract. A 69-year-old man was found to have multiple liver tumors and was referred to our hospital. He had a history of chronic hepatitis C, but HCV-RNA was negative and AFP and PIVKA-II were not elevated. Metastatic liver tumors were suggested by abdominal dynamic CT and ultrasonography. Multiple small blackish spots were detected in the gastrointestinal tract. Malignant melanoma was diagnosed by biopsy from the liver tumor and the gastrointestinal tract and remarkable elevation of 5-S-CD 436.4 nmol/l. A blackish, slightly elevated lesion was detected in the oral cavity and was thought to be primary site. The patient chose palliative therapy and died 69 days after his first visit to his local doctor.

Nakamuta M, Kotoh K, Enjoji M, Kajiwara E, Shimono J, Masumoto A, Maruyama T, Furusyo N, Nomura H, Sakai H, Takahashi K, Azuma K, Shimoda S, Tanabe Y, Hayashi J. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Japan. · Comp Hepatol. · Pubmed #17470300 links to  free full text

Abstract: BACKGROUND: Lamivudine treatment has been recently demonstrated to increase the serum albumin levels in cirrhotic patients with hepatitis B virus (HBV) infection, but the precise mechanism remains unclear. We hypothesized that the improvement of hypoalbuminemia by lamivudine may be attributable to the reduction of HBV replication itself, rather than to cessation of hepatitis. In order to confirm this hypothesis, in this study we evaluated factors which correlated with the increase in serum albumin levels. Fifty-four patients (Child-Pugh A/B/C, 35/9/10) with HBV-related liver cirrhosis who had been treated with lamivudine for more than 12 months were evaluated. We analyzed the correlation between the increase in serum albumin levels at month 12 after starting treatment (Delta-albumin) and various pretreatment variables. We also analyzed the correlation between Delta-albumin and the reduction in serum levels of HBV-DNA (Delta-HBV-DNA) or alanine aminotransferase (Delta-ALT) at month 12. RESULTS: The average Delta-albumin was 0.38 g/dL and only serum HBV-DNA levels before treatment correlated significantly with Delta-albumin. We also analyzed the correlation in patients whose alanine aminotransferase levels were normalized after 12 months so that the possible influence of breakthrough hepatitis could be excluded. Even among this subgroup of patients, there was no significant correlation between Delta-albumin and either pretreatment alanine aminotransferase levels or Delta-ALT. In contrast, in patients whose serum HBV-DNA was undetectable at month 12, we found a significant correlation between Delta-albumin and both pretreatment serum HBV-DNA levels and Delta-HBV-DNA. CONCLUSION: Our results demonstrated that albumin levels are associated with pretreatment HBV-DNA but not with alanine aminotransferase levels.

Lan RY, Cheng C, Lian ZX, Tsuneyama K, Yang GX, Moritoki Y, Chuang YH, Nakamura T, Saito S, Shimoda S, Tanaka A, Bowlus CL, Takano Y, Ansari AA, Coppel RL, Gershwin ME. · Division of Rheumatology, Allergy, and Clinical Immunology, University of California--Davis, Davis, CA 95616, USA. · Hepatology. · Pubmed #16557534 No free full text.

Abstract: CD4+CD25high regulatory T cells (Tregs) play a critical role in self-tolerance, as seen in murine autoimmunity. Studies on Tregs in human autoimmunity have focused primarily on peripheral blood samples. A study targeting diseased tissue should identify direct relationships between Tregs and autoimmunity. Peripheral blood samples were collected from 91 patients with primary biliary cirrhosis (PBC), 28 immediate relatives, and 41 healthy controls, and Treg frequencies were determined as a percentage of CD4+CD25high T cells in CD4+TCR-alphabeta+ T cells. A tissue-targeted determination of frequency and distribution of FoxP3+ Tregs was also performed on 90 different liver tissue specimens exhibiting PBC (n = 52), chronic hepatitis C (CHC) (n = 30), and autoimmune hepatitis (AIH) (n = 8). Treg suppression studies were performed on 50 PBC patients and 27 controls. Patients with PBC demonstrated a relative reduction of Tregs compared with controls (P < .0002). Interestingly, a deficiency in CD4+CD25+ Tregs was also found in the daughters and sisters of PBC patients compared with controls (P < .0007). However, functional studies did not reveal a global PBC Treg defect. The level of FoxP3-expressing Tregs was markedly lower in affected PBC portal tracts compared with CHC and AIH (P < .001). In addition, the CD8+T cell/FoxP3+ Treg ratio was significantly higher in livers of late-stage PBC compared with those of CHC (P < .001) and early-stage AIH (P < .001). In conclusion, these data provide support for a genetic modulation of Treg frequency and illustrate the role Tregs play in the loss of tolerance in PBC.

Furusyo N, Takeoka H, Toyoda K, Murata M, Tanabe Y, Kajiwara E, Shimono J, Masumoto A, Maruyama T, Nomura H, Nakamuta M, Takahashi K, Shimoda S, Azuma K, Sakai H, Hayashi J. · Department of General Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka 812-8582, Japan. · World J Gastroenterol. · Pubmed #16489669 links to  free full text

Abstract: AIM: To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS: In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 (median 21) mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment.RESULTS: Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL (P<0.0001), HBeAg negativity (P<0.0001), a platelet count of 100 x 10(9)/L or more (P=0.0162) at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment (P=0.0003) to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at >=5 mo. A virological breakthrough was found significantly more often in patients with delayed virological response.CONCLUSION: Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.

Nakamuta M, Morizono S, Tanabe Y, Kajiwara E, Shimono J, Masumoto A, Maruyama T, Furusyo N, Nomura H, Sakai H, Takahashi K, Azuma K, Shimoda S, Kotoh K, Enjoji M, Hayashi J, Anonymous00143. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-5282, Japan. · World J Gastroenterol. · Pubmed #16437598 links to  free full text

Abstract: AIM: To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation. METHODS: We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year (n = 249), two years (n = 147), and three years (n = 72) were evaluated from the levels of serum ALT and HBV-DNA, as biological and virological effects (undetectable levels by PCR), respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed. RESULTS: For 1-year treatment, multivariate analysis revealed that BSA (P = 0.0002) was the only factor for the biological effect, and that ALT (P = 0.0017), HBV-DNA (P = 0.0004), and HBeAg (P = 0.0021) were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA (P = 0.0147) was the only factor for the biological effect, and that ALT (P = 0.0192) and HBeAg (P = 0.0428) were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA (P = 0.0730) as a factor for the normalization of ALT levels. CONCLUSION: BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.

Hiramatsu S, Maruyama T, Ito H, Shimoda S, Kaji Y, Harada M. · Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Japan. · Int Heart J. · Pubmed #16394599 links to  free full text

Abstract: Although interferon (IFN) shows cardiotoxicity and arrhythmogenesis, the influence of IFN on signal-averaged electrocardiography remains to be clarified. The aim of this study was to test a clinical hypothesis that IFN therapy for hepatitis C virus may induce ventricular late potentials (LPs) and related arrhythmias in patients with chronic active hepatitis. Signal-averaged and ambulatory electrocardiograms were recorded sequentially in patients with chronic active hepatitis C (n = 22) throughout the entire period of IFN therapy. The filtered QRS duration (fQRS) and low amplitude (< 40 microV) signal duration (LAS40) were significantly increased (95.5 +/- 8.5 to 99.6 +/- 9.4 msec, P < 0.0001, and 32.8 +/- 3.1 to 36.3 +/- 3.0 msec, P < 0.0001, respectively), whereas the root mean square voltage in the terminal 40 msec of the fQRS (RMS40) was significantly decreased (25.5 +/- 5.4 to 22.3 +/- 5.2 microV, P < 0.005) 1 month after starting the IFN therapy. The ventricular LP was negative in all subjects before starting therapy, but became positive in 7 patients after the therapy commenced. There were no differences in clinical baseline characteristics between the LP-positive (n = 7) and LP-negative (n = 15) groups. Significant increases in mean heart rate, fQRS, and LAS40 were observed after starting the therapy, irrespective of the appearance of the ventricular LP, whereas a decrease in RMS40 was observed only in the LP-positive group. No sustained ventricular arrhythmias were documented in the ambulatory electrocardiography and no cardiac events were encountered in the follow-up period. Therefore, the results indicate a reversible and subclinical risk of IFN-induced arrhythmogenesis.

Nakamura M, Takii Y, Ito M, Komori A, Yokoyama T, Shimizu-Yoshida Y, Koyabu M, Matsuyama M, Mori T, Kamihira T, Daikoku M, Migita K, Yatsuhashi H, Nozaki N, Shimoda S, Ishibashi H. · Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan. · J Autoimmun. · Pubmed #16337775 No free full text.

Abstract: The sustained antibody response to nuclear envelope gp210 antigen indicates a group of primary biliary cirrhosis (PBC) patients at high risk for the progression to end-stage hepatic failure. To address this issue, we immunohistochemically studied the expression of gp210 antigen in needle liver biopsy specimens from PBC patients using a monoclonal antibody specific for gp210 antigen. The specimens from autoimmune hepatitis (AIH), chronic viral hepatitis B (CHB) and C (CHC) patients served as disease controls. The expression of gp210 antigen was apparently increased on the nuclear envelope of biliary epithelial cells (BECs) of small bile ducts in almost all specimens from PBC. In contrast, the expression of gp210 antigen was negative in BECs of small bile ducts in normal liver, while relatively weak anti-gp210 immunostaining was observed in AIH, CHC and CHB. In addition, the degree of gp210 expression in BECs of small bile ducts was positively correlated to that of portal inflammation, interface hepatitis and lobular inflammation in PBC. These results indicate that the increased expression of gp210 in small bile ducts, which is probably associated with damage to BECs by inflammation, is possibly involved in autoimmune response to gp210 leading to the progression to end-stage hepatic failure in PBC.

Isse K, Harada K, Zen Y, Kamihira T, Shimoda S, Harada M, Nakanuma Y. · Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. · Hepatology. · Pubmed #15726664 No free full text.

Abstract: Fractalkine is a chemokine with both chemoattractant and cell-adhesive functions, and in the intestine it is involved with its receptor CX3CR1 in the chemoattraction and recruitment of intraepithelial lymphocytes. We examined the pathophysiological roles of fractalkine and CX3CR1 in normal and diseased bile ducts. Expression of fractalkine and CX3CR1 were examined in liver tissues from patients with primary biliary cirrhosis (17 cases) and controls (9 cases of primary sclerosing cholangitis, 10 cases of extrahepatic biliary obstruction, 20 cases of chronic viral hepatitis C, and 18 cases of histologically normal livers). Expression of fractalkine in biliary epithelial cells (BECs) in response to cytokine treatments was examined using a human cholangiocarcinoma cell line (HuCC-T1) and human intrahepatic BEC line. The chemotaxis of CX3CR1-expressing monocytes (THP-1) toward fractalkine was assayed using chemotaxis chambers. Fractalkine messenger RNA/protein were expressed on BECs of normal and diseased bile ducts, and their expression was upregulated in injured bile ducts of primary biliary cirrhosis. CX3CR1 was expressed on infiltrating mononuclear cells in portal tracts and on CD3(+), CD4(+), and CD8(+) intraepithelial lymphocytes of injured bile ducts in primary biliary cirrhosis. Fractalkine messenger RNA expression was upregulated in two cultured BECs on treatment with lipopolysaccharide and Th1-cytokines (interleukin 1beta, interferon gamma, and tumor necrosis factor alpha). THP-1 cells showed chemotaxis toward fractalkine secreted by cultured cells. In conclusion, Th1-cytokine predominance and lipopolysaccharide in the microenvironment of injured bile ducts resulting from primary biliary cirrhosis induce the upregulation of fractalkine expression in BECs, followed by the chemoattraction of CX3CR1-expressing mononuclear cells, including CD4(+) and CD8(+) T cells, and their adhesion to BECs and the accumulation of biliary intraepithelial lymphocytes.

Nakamura M, Shimizu-Yoshida Y, Takii Y, Komori A, Yokoyama T, Ueki T, Daikoku M, Yano K, Matsumoto T, Migita K, Yatsuhashi H, Ito M, Masaki N, Adachi H, Watanabe Y, Nakamura Y, Saoshiro T, Sodeyama T, Koga M, Shimoda S, Ishibashi H. · Department of Hepatology, Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Kubara 2-1001-1, Omura, Nagasaki 856-8562, Japan. · J Hepatol. · Pubmed #15710222 No free full text.

Abstract: BACKGROUND/AIMS: The presence of antibodies to the 210-kDa glycoprotein of the nuclear pore complex (gp210) is highly indicative of primary biliary cirrhosis (PBC). However, the significance of anti-gp210 antibody titers for monitoring PBC remains unresolved. METHODS: We used an ELISA with a gp210 C-terminal peptide as an antigen to assess serum antibody titers in 71 patients with PBC. RESULTS: Patients were classified into three groups: Group A in whom anti-gp210 titers were sustained at a high level, Group B in whom anti-gp210 status changed from positive to negative under ursodeoxycholic acid (UDCA) therapy, Group C in whom anti-gp210 antibodies were negative at the time of diagnosis. The rate of progression to end-stage hepatic failure was significantly higher in group A (60%) as compared to groups B (0%) and C (4.2%). The sustained antibody response to gp210 was closely associated with the severity of interface hepatitis. The significance of anti-gp210 antibody was confirmed by National Hospital Organization Study Group for Liver Disease in Japan. CONCLUSIONS: The serial quantitation of serum anti-gp210-C-terminal peptide antibodies is useful for monitoring the effect of UDCA and for the early identification of patients at high risk for end-stage hepatic failure.