Autoimmune responses as assessed by hypergammaglobulinemia and the presence of autoantibodies in patients with chronic hepatitis C.

We investigated autoimmunity, as assessed by hypergammaglobulinemia and the presence of autoantibodies including anti-nuclear antibodies (ANA) and anti-liver membrane antibodies (LMA), in 149 patients with chronic hepatitis C, 55 patients with chronic hepatitis B and 11 patients with autoimmune hepatitis. There was no significant difference in the incidence of these autoantibodies between chronic hepatitis C and chronic hepatitis B. Nine patients with chronic hepatitis C satisfied the serological criteria of autoimmune hepatitis (ANA positive and gammaglobulin or serum IgG greater than 2500 mg/dl), but none of the patients with chronic hepatitis B met the criteria. This suggests that autoimmunity is greater in chronic hepatitis C than in chronic hepatitis B. Of the 9 patients with chronic hepatitis C, all 4 patients tested for human leukocyte antigen (HLA) phenotype had HLA-DR4, which is known to be associated with autoimmune hepatitis in Japanese patients. We believe that hepatitis C virus (HCV) infection enhances the initiation and perpetuation of autoimmunity in susceptible individuals

Specificities and Clinical Significance of Anti-Cytoskeleton Antibodies in Anti-Smooth Muscle Antibody-Positive Patients with Chronic Liver Disease C

We investigated the specificities and characteristics of anti-cytoskeleton antibodies in 13 anti-smooth muscle antibody (ASMA)-positive patients with chronic liver disease C (CLD-C), and compared them with those in 7 ASMA-positive patients with autoimmune hepatitis (AIH), and 6 ASMA-positive patients with chronic liver disease B (CLD-B). Anti-microfilaments (anti-MF) were found not only in 6/7 AIH patients (85.7%), but also in 8/13 CLD-C patients (61.5%) with a relatively high incidence, when compared with 1/6 CLD-B patients (16.7%), while, there was no significant difference in the incidence of anti-intermediate filaments (anti-IMF), especially anti-IMF IgM, among these patient groups. Among the patients with CLD-C, the mean levels of serum gammaglobulin and IgG in the anti-MF-positive patients were 2.46 +/- 1.03 g/dl and 3277 +/- 1089 mg/dl, respectively, which were higher than those in the anti-MF-negative patients (1.60 +/- 0.53 g/dl, 2245 +/- 610 mg/dl) and those in the patients with CLD-B (1.60 +/- 0.57 g/dl, 2192 +/- 339 mg/dl). Furthermore, 4 of the 8 anti-MF-positive patients with CLD-C satisfied the serological criteria for the diagnosis of AIH. These findings suggest that autoimmune mechanisms might be involved in the pathogenesis of anti-MF-positive CLD-C, and that anti-MF might be used as a marker

Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients

<p>Abstract</p> <p>Background</p> <p>Hepatitis B virus (HBV) is a major cause of hepatocarcinogenesis.</p> <p>To identify mutations relevant to hepatocellular carcinoma (HCC) development, we compared the full genome sequences of HBV from the sera of patients with and without HCC.</p> <p>Methods</p> <p>We compared the full genome sequences of HBV isolates from 37 HCC patients (HCC group 1) and 38 patients without HCC (non-HCC group 1). We also investigated part of the core promoter region sequences from 40 HCC patients (HCC group 2) and 68 patients without HCC. Of the 68 patients who initially did not have HCC, 52 patients remained HCC-free during the follow-up period (non-HCC group 2), and 16 patients eventually developed HCC (pre-HCC group 2). Serum samples collected from patients were subjected to PCR, and the HBV DNA was directly sequenced.</p> <p>Results</p> <p>All patients had genotype C. A comparison of the nucleotide sequences of the HBV genome between HCC group 1 and non-HCC group 1 revealed that the prevalence of G1613A and C1653T mutations in the core promoter region was significantly higher in the HCC group. These mutations tended to occur simultaneously in HCC patients. Multivariate analysis with group 2 revealed that the presence of HCC was associated with aging and the double mutation. Future emergence of HCC was associated with aging and the presence of a single G1613A mutation.</p> <p>Conclusions</p> <p>G1613A and C1653T double mutations were frequently found in patients with HCC. A single G1613A mutation was associated with future emergence of HCC. These mutations may serve as useful markers in predicting HCC development.</p

A homosexual japanese man with acute hepatitis due to hepatitis B virus genotype ae, concurrent with amebic colitis

We report herein a case with acute hepatitis due to hepatitis B virus genotype Ae, concurrent with amebic colitis. A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice. Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen. The hepatitis B virus genotype was determined to be Ae. Furthermore, a mud-like stool with blood and mucous had sometimes been noted during the past 3 years, and amebic colitis was shown by colonofi berscopy during hospitalization. The patient was diagnosed with acute hepatitis B, concurrent with amebic colitis, and was successfully treated with lamivudine and metronidazole. In Japanese patients with acute hepatitis B virus genotype A infection, homosexual activity tends to be high. Furthermore, in Japanese homosexual men, amebiasis has been increasing. Thus, in Japanese patients with acute hepatitis B, a determination of genotype should be performed in order to investigate the route of transmission of hepatitis B virus, and a search for amebiasis should be performed in patients with acute hepatitis due to hepatitis B virus genotype A. Furthermore, education of homosexual men regarding hepatitis B virus, hepatitis B virus vaccination, and amebiasis is urgently required

Effectiveness of Extending Treatment Duration in Therapy with Pegylated Interferon and Ribavirin for Genotype 2 Hepatitis C Virus Infection

The effectiveness of extending treatment duration as response guided therapy was previously reported for chronic hepatitis C (CHC) genotype 1, but is still controversial for genotype 2. The present study is a retrospective cohort study to investigate the effectiveness of extending treatment duration in therapy with pegylated interferon and ribavirin for patients with CHC genotype 2 by focusing on the timing at which patients obtained undetectable HCV RNA. A total of 306 patients who obtained undetectable HCV RNA by week 24 of treatment and completed 24 weeks of treatment were enrolled. Rapid virological response (RVR) to standard therapy was achieved by 122 patients (51ｵ), and 89ｵ of them obtained sustained virological response (SVR), while 69ｵ of non-RVR patients achieved SVR. Non-RVR patients with undetectable HCV RNA at week 8, and insufficient adherence＜80ｵ pegylated interferon and ribavirin during the first 24 weeks, significantly improved their SVR rate by extended therapy. Among patients receiving extended therapy, drug adherences did not differ between SVR and non-SVR patients, indicating that extending treatment duration might compensate for insufficient antiviral effects due to insufficient drug adherences. This finding might be useful in creating a guideline for extending treatment duration for patients with CHC genotype 2

Consideration of impact factors on data acquisition for ocean radar with VHF band

An ocean radar with a VHF band is a useful tool for surveying coastal currents in a wide area. We have conducted a field observation of currents in Ariake Bay, the large inner sea located in the western part of Japan. Although the number of valid data acquired (hereafter, data acquisition) varies temporally and spatially, the mechanism of such variation is not yet well understood. Our aim in this study is to investigate the impact factor affecting data acquisition through field observations of current, salinity and wind in Ariake Bay. As a result, the data acquisition and the maximum measurement distance of the radar decreased owing to the decreases in salinity and wind speed. After receiving much rainfall, the data acquisition decreased rapidly in accordance with the decrease in surface salinity influenced by run-off from adjacent rivers and a flood control dike. Also, when wind speed became less than 2 m/s, the intensity of the signals received was not sufficient for the detection of current velocity. In conclusion, salinity and wind speed are important factors for steady-current observation using ocean radars.2008 International Conference on Radar (Radar 2008) : Adelaide, 2008.09.2-2008.09.

Laparoscopic findings of reddish markings predict hepatocellular carcinoma in patients with hepatitis B virus-related liver disease

For patients with chronic hepatitis due to hepatitis B virus (HBV), factors predicting hepatocellular carcinoma (HCC) other than high levels of HBV-DNA and alanine aminotransferase (ALT) are needed to prevent HCC development, as many patients with chronic HBV infection fulfill these conditions. The purpose of this study was to clarify factors predictive of HCC development for those patients. The study was a systematic cohort analysis of 303 consecutive patients with hepatitis B e-antigen, receiving laparoscopic examination for assessment of liver disease. Laparoscopic, histological, and clinical characteristics were investigated as related to HCC development. HCC occurred in 27 patients during a mean follow-up of 8.0 +/- A 5.0 years, at the age of 37-72 years. Significant associations with HCC development were shown for liver cirrhosis, histological activity grade, reddish markings, and older age. Multivariate analysis revealed that HCC development was strongly associated with older age and male gender (P = 0.002 and P = 0.043, respectively). HCC occurred more frequently in patients of age a parts per thousand yen30 years even with early stage than in patients of age < 30 years (P = 0.031). Severe reddish markings, a laparoscopic finding of widespread parenchymal destruction, were highly associated with HCC development in patients of age a parts per thousand yen30 years at diagnosis (odds ratio = 1.67, P = 0.034), while histological activity grade and ALT level were not (P = 0.075 and P = 0.69, respectively). HCC development is associated with older age, male gender, and liver cirrhosis. Reddish markings, rather than histological activity or ALT level, can be useful to predict HCC for HBV patients of age a parts per thousand yen30 years

Medium Effects in Coherent Pion Photo- and Electroproduction on 4He and 12C

Coherent pi0 photo- and electroproduction on 4He and 12C nuclei is investigated in the framework of a distorted wave impulse approximation in momentum space. The elementary process is described by the recently developed unitary isobar model. Medium effects are considered by introducing a phenomenological Delta self-energy. The recent experimental data for 4He and 12C can be well described over a wide range of energies and emission angles by the assumption that the Delta-nuclear interaction saturates.Comment: 18 pages LaTeX including 7 postscript figure

Proteolytic Processing of Stat6 Signaling in Mast Cells as a Negative Regulatory Mechanism

Accumulating evidence has shown the importance of Stat6-mediated signaling in allergic diseases. In this study, we show a novel regulatory mechanism of Stat6-mediated signaling in mast cells. When Stat6 is activated by interleukin (IL)-4 and translocated to the nucleus, Stat6 is cleaved by a nucleus-associated protease in mast cells. The cleaved 65-kD Stat6 lacks the COOH-terminal transactivation domain and functions as a dominant-negative molecule to Stat6-mediated transcription. The retrovirus-mediated expression of cleavage-resistant Stat6 mutants prolongs the nuclear accumulation of Stat6 upon IL-4 stimulation and enhances IL-4–induced gene expression and growth inhibition in mast cells. These results indicate that the proteolytic processing of Stat6 functions as a lineage-specific negative regulator of Stat6-dependent signaling in mast cells, and thus suggest that it may account for the limited role of Stat6 in IL-4 signaling in mast cells

Entecavir Reduces Hepatocarcinogenesis in Chronic Hepatitis B Patients

Chronic hepatitis B (CHB) leads to cirrhosis and hepatocellular carcinoma (HCC). With a cohort of 1,206 CHB patients who visited Okayama University Hospital and related hospitals in 2011 and 2012, we compared the incidence rates of HCC among the patients grouped by age, hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), and treatment. HCCs were observed in 115 patients with the median observation period of 1,687 days. Among the HCC patients aged &#8805; 35 years, HBV DNA &#8805; 4 log copies/mL and positive HBeAg at diagnosis (n=184), the HCC incidence rate was 8.4% at 5 years in the entecavir (ETV)-treated patients, 21.8% in the lamivudine (LVD)-treated patients, and 26.4% among the patients not treated with drugs. The cumulative HCC incidence was significantly reduced in the ETV-treated patients compared to those treated with LVD or not treated (p=0.013). Among the patients aged &#8805; 35 years with HBV DNA &#8805; 4 log copies/mL and negative HBeAg (n=237), the cumulative HCC incidence was 14.6% in 5 years in ETV group and 13.9% among those not treated with a drug (p>0.05). Only small numbers of HCCs occurred in other patients. In CHB patients aged&#8805;35 years with HBV DNA &#8805;4 log copies/mL and positive HBeAg, ETV treatment is recommended for the suppression of HCC development