Mesoporous activated carbons (ACs) were prepared from bamboo by phosphoric acid activation, and the optimum activation conditions such as impregnation ratio (H3PO4/bamboo ratio) and activation temperature were examined. The pore structure of the ACs was determined by N2 adsorption-desorption isotherms. The results showed that the AC prepared using an impregnation ratio of 3 g/g and an activation temperature of 500 °C had the highest mesopore volume of 0.93 cm3/g. For further development of pores in AC, alkali pretreatment of the bamboo by soaking in aqueous sodium hydroxide was conducted and the pretreated bamboo was then activated with phosphoric acid under the optimum conditions. The influences of alkali pretreatment on the components of the raw material and the pore structure of the AC were examined, and the properties of bamboo before and after alkali pretreatment were also evaluated by thermogravimetric analysis and scanning electron microscopy. As a result, the possibility of the elution of hemicellulose and lignin from bamboo by alkali pretreatment was suggested. The AC prepared from alkali-pretreated bamboo had a mesopore volume of as high as 1.50 cm3/g, suggesting that the elution of hemicellulose and lignin from the raw material contributes to the development of mesopores by phosphoric acid activation.
BACKGROUND AND AIMS Genetic factors associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), immune-mediated chronic inflammatory liver diseases of unknown etiology, remain to be elucidated. Polymorphisms of the gene encoding Fas have been linked to a variety of autoimmune diseases. We hypothesized that Fas gene polymorphisms might be genetic markers for AIH and PBC. METHODS To determine the frequency and significance of Fas polymorphisms in patients with AIH and PBC, 74 Japanese AIH patients, 98 Japanese PBC patients, and 132 ethnically matched control subjects were investigated by the use of the Taqman assay. RESULTS We found significant differences between AIH patients and controls in allele frequencies of Fas-670 (p = 0.009), Fas IVS (intervening sequence) 2nt176 (p = 0.018), Fas IVS3nt46 (p = 0.031), and Fas IVS5nt82 (p = 0.013) polymorphisms. Haplotype analysis revealed that one of the haplotypes, GATGC, was associated with increased AIH prevalence. On the other hand, we found no statistically significant differences between PBC patients and controls in allele frequencies of the Fas polymorphisms genotyped in this study. CONCLUSIONS These results indicate a genetic link of Fas polymorphisms to the development of AIH. Further studies are needed to determine the genetic factors contributing to the development of AIH.
<i>Objective: </i>Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation in tumor cells. The effect of the HDAC inhibitor, trichostatin A (TSA), on hepatoma cells, however, has not been well studied. In this study, we examined cell viability and gene expression profile in hepatoma cell lines treated with TSA. <i>Methods:</i> To study cell growth inhibition and induction of apoptosis by TSA on human hepatoma cell lines including HuH7, Hep3B, HepG2, and PLC/PRF/5, cells were treated with TSA at various concentrations and analyzed by the 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively. Changes in gene expression profile after exposure to TSA were assessed using a cDNA microarray consisting of 557 distinct cDNA of cancer-related genes. The levels of acetylated histones were examined by the chromatin immunoprecipitation (ChIP) assay using anti-acetylated histone H3 or H4 antibody. <i>Results:</i> The MTT assay demonstrated that TSA showed cell growth inhibition not only in a concentration-dependent but also a time-dependent manner on all cell lines studied. The TUNEL assay also revealed the potential of TSA to induce apoptosis. The microarray analysis revealed that 8 genes including collagen type 1, α2 (COL1A2), insulin-like growth factor binding protein 2 (IGFBP2), integrin, α7 (ITGA7), basigin (BSG), quiescin Q6 (QSCN6), superoxide dismutase 3, extracellular (SOD3), nerve growth factor receptor (NGFR), and p53-induced protein (PIG11) exhibited substantial induction (ratio >2.0) after TSA treatment in multiple cell lines. ChIP assay, in general, showed a good correlation between the expression level of mRNA and levels of acetylated histones in these upregulated genes. <i>Conclusions:</i> This study showed cell growth inhibition and the gene expression profile in hepatoma cell lines exposed to TSA. The alteration in levels of acetylated histones was closely associated with expression of specific cancer-related genes in hepatoma cells.
One point mutation to make a stop codon in the precore (pre-C) region of the hepatitis B virus DNA in anti-HBe-positive patients has been reported recently. This mutation disturbs the formation of the pre-C protein that is processed to make HBeAg. The relationship between the point mutation and HBe antigen antibody status was investigated in B-viral liver diseases. The pre-C region was amplified by a polymerase chain reaction (PCR) method and the nucleotide sequences were determined by a direct sequencing method. In seven cases who were persistently HBeAg-positive, the wild type (no mutation in pre-C region) was detected in all. In 20 cases who were anti-HBeAg-positive at diagnosis, the mutant type (point mutation at nucleotide 1896 in pre-C region, which makes a stop codon) was detected in 16 cases and the wild type in two cases. In HBe seroconversion (SC) cases, the types of virus were investigated in serial blood samples. No mutant type was detected in initial sera during the HBeAg-positive period. In two 'natural' SC cases, the mutant type appeared before anti-HBe formation. However, in three anti-viral 'drug-induced' SC cases, the mutant type appeared after the formation of anti-HBe. In two 'reversed' seroconversion cases only the wild type was detected throughout the follow-up period. These data suggest that the appearance of a pre-C mutant may help to predict seroconversion from HBeAg to anti-HBe and may help distinguish 'natural' and 'drug-induced' seroconversion of HBeAg.
The use of phlebotomy is relatively common for 'difficult-to-treat by antiviral therapies' hepatitis C virus (HCV)-infected patients and for certain patients having chronic liver diseases with an iron overload of the liver. In the present study, we retrospectively analyzed patients treated with phlebotomy and their adverse events. We observed the occurrence and recurrence of hepatocellular carcinoma, and the appearance of ascites in some patients infected with HCV as well as the reduction of serum ferritin and alanine aminotransferase levels. Severe adverse events necessitating a cessation of phlebotomy occurred independently of α-fetoprotein (>10 ng/ml) in patients infected with HCV according to multivariate logistic regression analysis. These findings may serve as a basis for phlebotomy especially in older patients with chronic hepatitis C.
The aim of this study is to detect the possible association of hepatitis B virus (HBV) core mutation, hepatitis B e antigen (HBeAg) status and the viral load in chronic hepatitis B (CHB) patients. Sixty-six patients with CHB were enrolled. Hepatitis markers and hepatitis C virus antibody (HCV-Ab) were tested using micro particle enzyme immunoassay kits. Viral load was measured by real-time polymerase chain reaction (PCR) and the mutation was analyzed by nested PCR followed by restriction fragment length polymorphism. Most of CHB patients were HBeAg (−ve). The HBeAg status did not have an influence on the presence or absence of T1762/A1764 mutation. HBV-DNA serum level was not significantly different in patients with core mutation and patients without core mutation in HBeAg (−ve) group, while in HBeAg (+ve) group HBV-DNA serum level was significantly higher in patients with core mutation. This study reports the predominance of HBeAg (−ve) and HBV core promoter mutation.
// Yuki Haga 1 , Tatsuo Kanda 1,2 , Shin Yasui 1 , Masato Nakamura 1 , Yoshihiko Ooka 1 , Koji Takahashi 1 , Shuang Wu 1 , Shingo Nakamoto 1,3 , Makoto Arai 1 , Tetsuhiro Chiba 1 , Hitoshi Maruyama 1 , Osamu Yokosuka 1 , Nobuo Takada 4 , Mitsuhiko Moriyama 2 , Fumio Imazeki 1,5 and Naoya Kato 1 1 Department of Gastroenterology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan 2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan 3 Department of Molecular Virology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan 4 Department of Internal Medicine, Toho University Sakura Medical Center, Shimoshizu, Sakura, Japan 5 Safety and Health Organization, Chiba University, Yayoicho, Inage-ku, Chiba, Japan Correspondence to: Tatsuo Kanda, email: // Keywords : hepatitis C virus; direct-acting antiviral failure; non-structural 5A (NS5A) inhibitors; resistance-associated variants; case reports Received : June 20, 2017 Accepted : December 23, 2017 Published : December 29, 2017 Abstract Background: Interferon-free treatment results in higher sustained virologic response (SVR) rates, with no serious adverse events in hepatitis C virus (HCV)-infected patients. However, in some patients with treatment-failure in HCV NS5A inhibitor-including interferon-free regimens, the treatment-emergent HCV NS5A resistance-associated variants (RAVs), which are resistant to interferon-free retreatment including HCV NS5A inhibitors, are observed. In HCV-infected Japanese patients with daclatasvir and asunaprevir treatment failure, retreatment with sofosbuvir and ledipasvir could lead to only ~70% SVR rates. Case summary: Three HCV genotype (GT)-1b-infected cirrhotic patients who discontinued the combination of daclatasvir and asunaprevir due to adverse drug reactions within 4 weeks; retreatment with sofosbuvir and ledipasvir combination could result in SVR in these patients without RAVs. One HCV GT-1b-infected cirrhotic patient who discontinued the combination of daclatasvir and asunaprevir due to viral breakthrough at week 10; retreatment with sofosbuvir and ledipasvir combination for this patient with the treatment-emergent HCV NS5A RAV-Y93H resulted in viral relapse at week 4 after the end of the treatment. Conclusion: Retreatment with sofosbuvir and ledipasvir is effective for HCV GT-1b patients who discontinue the combination of daclatasvir and asunaprevir within 4 weeks. The treatment response should be related to the existence of treatment-emergent HCV NS5A RAVs, but may not be related to the short duration of treatment.
Summary The short‐term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks ( P = 0.02) and 4 weeks ( P < 0.01). Mean reduction in HBV DNA during the first 2 weeks was 1.7 ± 0.9 log copies per mL in overall patients, 2.1 ± 0.8 in survived patients and 1.2 ± 0.9 in dead/transplanted patients. The decline of HBV DNA was significant between the first 2 weeks ( P = 0.03) and 4 weeks ( P = 0.02) in survived patients, but not in dead/transplanted patients. Our study shows that corticosteroid treatment in combination with nucleotide analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.
