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Hiroki Tahara,
Ken Sato,
Yuichi Yamazaki,
Tatsuya Ohyama,
Norio Horiguchi,
Hiroaki Hashizume,
Satoru Kakizaki, Hitoshi Takagi,
Iwata Ozaki,
Hideo Arai,
Junko Hirato,
Ralf Jesenofsky,
Atsushi Masamunes,
Masatomo Mori
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ABSTRACT: The role that transforming growth factor-α (TGF-α) has in chronic pancreatitis and pancreatic cancer has not been fully elucidated. We evaluated the effects of TGF-α on the human pancreatic stellate cell (PSC) line RLT-PSC and primary human PSCs, and the expression levels of TGF-α and metalloproteinase-1 (MMP-1) in human chronic pancreatitis and pancreatic cancer tissues. TGF-α stimulated the proliferation and migration of PSCs. Although the mRNA expression levels of tissue inhibitor of metalloproteinase-1 and α1(I) collagen were unchanged, the mRNA expression levels of MMP-1 increased concomitant with increases in MMP-1 protein levels and collagenase activity. TGF-α-stimulated migration of RLT-PSC cells was partially blocked by tissue inhibitor of metalloproteinase-1 protein and MMP-1 small interfering RNA. MMP-1 was also observed to stimulate the migration of PSCs. TGF-α-induced MMP-1 expression was completely blocked by gefitinib in PSCs. The Ras-ERK and PI3/Akt pathways appear to be involved in the activation of MMP-1 in PSCs. Immunohistochemical analyses showed that MMP-1 expression was significantly increased in the pancreatic interstitial tissues in case of chronic pancreatitis or pancreatic cancer compared with those in case of normal pancreas. In conclusion, TGF-α increased proliferation and migration of PSCs. TGF-α-induced migration of cells may be partly due to upregulation of MMP-1. TGF-α and MMP-1 upregulation may contribute to the pathogenesis of chronic pancreatitis and pancreatic cancer.Laboratory Investigation (2013) 0, 000-000. advance online publication, 22 April 2013; doi:10.1038/labinvest.2013.59.
Laboratory Investigation 04/2013; · 3.64 Impact Factor
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ABSTRACT: Background. The study aims to analyze in detail the incidence, mortality using the standardized incidence ratio (SIR), and standardized mortality ratio (SMR) of hepatocellular carcinoma (HCC) in primary biliary cirrhosis (PBC), because no large case studies have focused on the detailed statistical analysis of them in Asia. Methods. The study cohorts were consecutively diagnosed at Gunma University and its affiliated hospitals. Age- or sex-specific annual cancer incidence and deaths were obtained from Japanese Cancer Registry and Death Registry as a reference for the comparison of SIR or SMR of HCC. Moreover, univariate analyses and multivariate analyses were performed to clarify predictive factors for the incidence of HCC. Results. The overall 179 patients were followed up for a median of 97 months. HCC had developed in 13 cases. SIR for HCC was 11.6 (95% confidence interval (CI), 6.2-19.8) and SMR for HCC was 11.2 (95% CI, 5.4-20.6) in overall patients. The serum albumin levels were a predictive factor for the incidence of HCC in overall patients. Conclusions. The incidence and mortality of HCC in PBC patients were significantly higher than those in Japanese general population. PBC patients with low serum albumin levels were populations at high risk for HCC.
Gastroenterology Research and Practice 01/2013; 2013:168012. · 0.98 Impact Factor
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Takashi Hoshino,
Atsushi Naganuma, Hitoshi Takagi,
Eri Koitabashi,
Naomi Sakamoto,
Masahiro Inui,
Hiromitsu Souma,
Tomohiro Kudo,
Hiroshi Ishihara,
Akira Ogawa,
Masafumi Mizuide
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ABSTRACT: A 73-year-old man was admitted to a hospital with a complaint of epigastralgia and for evaluation of liver dysfunction. After hospitalization, he experienced disturbance of consciousness with septic shock, and was then transferred to our hospital. Computed tomography revealed dilatation of the intrahepatic bile duct and tumor of the middle bile duct. We diagnosed acute obstructive suppurative cholangitis. As a result, endoscopic nasobiliary drainage was performed, and the patient recovered. Based on pathological examinations of the bile duct biopsy specimen, the tumor was diagnosed as a carcinosarcoma. Consequently, the patient underwent pylorus-preserving pancreatoduodenectomy. However, 4 months after surgery, the patient died due to widespread metastasis of the carcinosarcoma. Preoperative diagnosis of carcinosarcoma of the bile duct is extremely rare. Our study suggests the efficacy of bile duct biopsy in such cases.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2013; 110(2):263-70.
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ABSTRACT: Cholangiocarcinoma (CCC) is the second most common type of primary liver cancer, and is associated with a high rate of mortality due to the difficulty of early detection and resistance to chemotherapeutic agents. To evaluate the possibility for new therapeutic strategies, we examined the combined effect of gefitinib and gemcitabine on CCC.
The effect of gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) signaling, gemcitabine, which is a pyrimidine analog, and the combined effect of gefitinib and gemcitabine on CCC cells were evaluated both in vitro and in vivo.
EGFR mRNA expression and phosphorylation of EGFR were elevated in both human CCC cell lines studied, HuCCT1 and RBE, suggesting EGFR signaling is up-regulated in CCC cell lines. Gefitinib treatment at high concentration inhibited the proliferation of the CCC cell lines. Furthermore, gefitinib reduced the transforming growth factor alpha (TGFα)-induced proliferation of these cells. Gemcitabine also suppressed the growth of the CCC cell lines in a concentration-dependent manner. The combination of gefitinib and gemcitabine synergistically suppressed the growth of the CCC cell lines and induced greater apoptosis compared to the use of either agent alone. As a mechanism for this effect, we found less phosphorylation of the extracellular signal-regulated kinase (ERK) protein, which means the suppression of EGFR signaling, when these compounds were administered together. Cell transplantation assay dramatically demonstrated the synergistic effect of this combination on HuCCT1 xenografts in vivo.
The combination of gefitinib and gemcitabine inhibited the proliferation of CCC cells via induction of apoptosis. The combination of EGFR inhibitor and additional chemicals could be a new therapeutic approach for CCC.
Anticancer research 12/2012; 32(12):5251-62. · 1.73 Impact Factor
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Satoru Kakizaki, Hitoshi Takagi,
Takeshi Ichikawa,
Takehiko Abe,
Toshihiko Yamada,
Keiji Suzuki,
Akira Kojima,
Hisashi Takayama,
Jirou Takezawa,
Takeaki Nagamine,
Masatomo Mori
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ABSTRACT: We examined the efficacy of interferon (IFN) therapy for chronic hepatitis C (CHC) in view of the change of liver histology
and iron staining before and after IFN therapy.
Enrolled in this study were 109 patients with CHC who completed IFN treatment and were followed for at least 1 yr after the
end of IFN therapy. Serum iron, unsaturated-iron-binding capacity (UIBC), and total-iron-binding capacity (TIBC) were assessed
before IFN therapy. Knodell’s histological activity index (HAI) score and iron staining were examined in 55 patients in whom
liver biopsy was performed at two points: before and 1 yr after IFN therapy. Serum iron levels before IFN therapy did not
correlate with the response to IFN. The HAI score significantly decreased after IFN therapy in complete responders (p<0.01) and biochemical responders (p<0.01). Three factors in the HAI, periportal necrosis, intralobular necrosis, and portal inflammation, but not fibrosis, were
significantly decreased in complete responders (p<0.01) and biochemical responders (p<0.01). Of 55 patients, 23 (41.8%) were positive for iron staining before IFN therapy and 14 of 55 (25.5%) after IFN therapy.
The positive rate for iron staining tended to decrease after IFN therapy, not correlating to the response to IFN, but the
change was not statistically significant.
In conclusion, the histological improvement by IFN therapy was mostly seen in necroinflammatory changes but not in fibrosis
at least 1 yr after IFN, and iron staining tended to decrease after IFN therapy.
Biological Trace Element Research 04/2012; 73(2):151-162. · 1.92 Impact Factor
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ABSTRACT: A 50-year-old female visited the hospital for further evaluation of multiple pulmonary and hepatic nodules. First, she visited
her primary physician for general fatigue due to anemia. She had recurrent epistaxis, and her mother had suffered from hereditary
hemorrhagic telangiectasia (HHT). Telangiectasias were present in the stomach. This patient was diagnosed with HHT. Computed
tomography (CT) revealed multiple pulmonary and hepatic nodules. The pulmonary nodules were due to bleeding from arteriovenous
malformations of the lung. Abdominal CT and angiography showed a dilated and meandering hepatic artery, arteriovenous shunts
and multiple hepatic nodules. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic
resonance imaging (MRI) showed enhancement in the early dynamic phase and in the liver-specific phase. A liver tumor biopsy
of a hepatic nodule showed nodular regenerative hyperplasia (NRH). This report presents a case of HHT with multiple pulmonary
and hepatic nodular lesions. Gd-EOB-DTPA-enhanced MRI was useful for making a diagnosis of NRH.
Clinical Journal of Gastroenterology 04/2012; 2(2):131-136.
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ABSTRACT: Proximal gastrectomy with jejunal interposition is a common surgical method in Japan, because the procedure has been shown
to give a better post-operative quality of life. Some complications are associated with it. However, esophageal candidiasis
and linear marginal ulcer along the gastrojejunal anastomosis after the surgical method has never previously been reported.
We herein report a case of a patient who developed serious complications after proximal gastrectomy with jejunal interposition.
A 68-year-old man underwent proximal gastrectomy with a jejunal pouch interposition for reconstruction for type 1 gastric
cancer. Twenty-three months after the procedure, he complained of dysphagia and epigastric pain. Esophagogastroduodenoscopy
showed esophageal candidiasis. The patient improved symptomatically following antifungal medication with fluconazole. Eleven
months later, the patient developed severe pneumonia. In subsequent days, a melena episode occurred. Esophagogastroduodenoscopy
revealed a linear marginal ulcer along three-fourths of the gastrojejunal anastomosis. The ulcer was drug resistant. The patient
died of respiratory failure. Jejunal pouch interposition after a proximal gastrectomy can be associated with significant complications.
Further studies are required to identify the best condition of the procedure.
Clinical Journal of Gastroenterology 04/2012; 2(3):183-186.
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ABSTRACT: We have evaluated the efficacy of interferon-α (IFN-α) plus zinc therapy in hepatitis C patients with genotype 1b, poor responders
for IFN alone. Ten patients were injected with 10 MU of IFN-α every day for 4 wk, followed by three times a week for 20 wk
(control group). Nine patients took 300 mg of zinc sulfate a day orally during IFN-α therapy (zinc sulfate group), and 15
patients took IFN-α and 150 mg of polaprezinc (polaprezinc group).
On the d 8 of IFN therapy, circadian zinc levels in serum elevated significantly in the polaprezinc group compared to the
zinc sulfate group or control group. Serum ALT levels normalized in 73.3% of the polaprezinc group, 55.6% of the zinc sulfate
group, and 40.0% of the control group at 6 mo after the end of IFN therapy. Sustained eradication for the hepatitis C virus
RNA judged at the end of the 6-mo follow-up period was higher in the polaprezinc group than in the zinc sulfate group (53.3%
vs 11.1%, p<0.05) or the control group (20.0%). No clinical side effects of zinc were observed at the dose used. The data suggest that
polaprezinc is expected to increase the therapeutic response of IFN-α for chronic hepatitis C with genotype 1b.
Biological Trace Element Research 04/2012; 75(1):53-63. · 1.92 Impact Factor
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ABSTRACT: Aims: Optimization of the duration of peginterferon-α/ribavirin therapy in patients with hepatitis C virus (HCV) genotype 2 and high viral loads remains to be established. We sought to prospectively optimize the treatment duration based on their virological responses. Methods: Serum HCV RNA levels of less than 50 IU/mL at weeks 2 and 4, and of 50 IU/mL or more at week 4, were defined as a super-rapid virological response (SRVR), rapid virological response (RVR) and late virological response (LVR), respectively. Treatment for 12, 24 or 48 weeks was assigned to the patients with an SRVR, RVR or LVR, respectively. However, patients with an LVR who expressed a desire to receive the standard therapy duration were given the 24-week therapy. Results: The overall sustained virological response (SVR) rate was 78.1% (118/151). The SVR rate in the SRVR group was 93.8% (15/16), which was comparable to the 93.0% (66/71) SVR rate in the RVR group. In the LVR patients, the 48-week treatment slightly increased the SVR rate to 76.5% (13/17) compared with the 51.1% (24/47) SVR rate in LVR patients who underwent the standard 24-week treatment. The relapse rate in LVR patients was significantly decreased in patients treated for 48 weeks compared with patients treated for 24 weeks. Multivariate analysis identified the predictive factors for SVR as RVR, prior interferon therapy and total peginterferon-α-2b adherence in patients treated for 24 weeks. Conclusion: Response-guided therapy may be effective and useful for optimization of the treatment duration.
Hepatology Research 03/2012; 42(9):854-63. · 2.20 Impact Factor
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Sho Ishiwata, Hitoshi Takagi,
Takashi Hoshino,
Atsushi Naganuma,
Naomi Sakamoto,
Eri Koitabashi,
Hiromitsu Souma,
Masayuki Inui,
Tomohiro Kudo,
Akira Ogawa,
Hiroki Tahara,
Mieko Kaneko,
Hiroaki Okamoto
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ABSTRACT: A woman in her seventies was admitted because of general fatigue and liver dysfunction (ALT 2565 IU/l). She was diabetic and, 2 months ago, began eating kikuimo (Jerusalem artichoke) containing inulin, which is thought to decrease blood sugar level. Although tests showed no evidence of acute infection of HAV, HBV, HCV, EBV and CMV, a drug-induced lymphocyte stimulation test using kikuimo extract was positive. She was first diagnosed with drug-induced liver injury according to the Japanese diagnostic criteria for the disease. After a non-eventful recovery, her serum was found to be positive for hepatitis E-antibody and RNA (genotype 3), indicating recent, autochthonous infection of HEV. The patient might have been misdiagnosed with drug-induced liver injury unless the serum test for HEV had been performed. We believe that HEV screening is mandatory for accurate diagnosis of hepatitis E and drug-induced liver injury.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2012; 109(4):624-9.
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ABSTRACT: BACKGROUND: Hepatocyte growth factor (HGF) is a potent growth factor involved in liver regeneration that has various effects on epithelial and nonepithelial cells. Although it has been demonstrated that HGF can reduce liver inflammation or fibrosis caused by pharmaceutical or chemical insult, no examination of its effect on liver injury in nonalcoholic steatohepatitis (NASH) has been reported. METHODS: To examine the effect of HGF on liver injury in NASH, we generated a murine steatohepatitis model on an HGF overexpression transgenic (Tg) background, and fed the mice a methionine- and choline-deficient diet (MCD). RESULTS: In mice fed the MCD diet, serum ALT levels and the inflammation score for the Tg mice were significantly lower than those for the wild-type (Wt) control mice (P < 0.01). The index of lipid peroxidation increased in the liver of the Wt mice as demonstrated by thiobarbituric acid-reactive substances. Furthermore, the liver fibrosis in Tg mice was dramatically suppressed in comparison to that in Wt mice. The gene expression of matrix metalloprotease-13 in the Tg mice was significantly increased in comparison to that of the Wt mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay showed the apoptotic cells to significantly decrease in number in the Tg mice in comparison to the Wt mice fed the MCD diet (P < 0.01). CONCLUSION: Hepatocyte growth factor ameliorated liver inflammation and fibrosis in a murine model of NASH as a result of the anti-oxidative and anti-apoptotic effect, and the induction of fibrinolysis.
Hepatology International 08/2011; · 2.64 Impact Factor
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ABSTRACT: This study evaluated whether the assessment of hepatitis C virus (HCV)-RNA at 12 weeks (FW+12) post-treatment follow-up was as applicable as FW+24 to evaluate sustained virological response (SVR) using the highly sensitive real-time polymerase chain reaction (PCR) HCV assay.
Two hundred and twenty-two patients with chronic hepatitis C were included in this study. Pegylated interferon (Peg-IFN) and ribavirin were administered for 24-72 weeks based on the genotype and viral load. Serum HCV-RNA was measured using real-time PCR at pretreatment, the end of treatment, FW+4, FW+8, FW+12, FW+16, FW+20 and FW+24. Two hundred patients had a virological response at the end of treatment. One hundred and forty-eight of 200 (74.0%) patients with a virological response at the end of treatment had an SVR at the FW+24. The positive predictive value (PPV) to identify patients with SVR at FW+4, FW+8, FW+12 was 87.1, 96.1, 98.0%, respectively. The viral load showed a reversion to the basal level as early as 8 weeks in relapse patients. There were only three patients who relapsed after FW+12 and all three of these patients were females with genotype Ib and a high viral load.
The assessment of serum HCV-RNA FW+12, using the highly sensitive real-time PCR assay, is almost as effective as FW+24 to predict SVR. However, there are false negatives in female patients with a high viral load of genotype Ib when the SVR is predicted by FW+12. The current standard with FW+24 is reasonable, but the assessment of serum HCV-RNA FW+12 may be effective in most patients.
Journal of Gastroenterology and Hepatology 06/2011; 27(1):69-75. · 2.87 Impact Factor
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Hiroki Tahara, Hitoshi Takagi,
Ken Sato,
Yasushi Shimada,
Hiroki Tojima,
Tomoyuki Hirokawa,
Tatsuya Ohyama,
Katsuhiko Horiuchi,
Atsushi Naganuma,
Hirotaka Arai,
Satoru Kakizaki,
Masatomo Mori
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ABSTRACT: Although partial splenic embolization (PSE) is reportedly effective prior to interferon (IFN)-based therapy, the number of subjects in these studies is small, and the appropriate candidates and disease prognosis remain unknown.
PSE was performed in 30 patients with advanced hepatitis C who could not receive IFN-based therapy because of thrombocytopenia, platelet counts of ≤100,000/mm(3), and hypersplenism. Also, we compared 25 PSE-treated patients with 23 PSE-untreated patients with thrombocytopenia receiving pegylated IFN (PEG-IFN)-alpha 2b plus ribavirin over the same period.
PSE significantly increased platelet and leukocyte counts. PSE was well tolerated with no severe complications. All the patients could receive IFN-based therapy. Discontinuation of therapy in the total cohort of PSE-treated patients was not due to thrombocytopenia. Although PSE did not significantly increase the sustained virological response (SVR) rate, it significantly maintained higher platelet counts throughout the observation period and increased the percentage of patients with 100% adherence to PEG-IFN in the total controlled study population and in subjects with genotype 2. In PSE-treated patients with genotype 2, a trend towards increased SVR was noted. Four patients developed hepatocellular carcinoma (HCC) at a median of 14.5 months after PSE, even though two of these patients had achieved an SVR.
IFN-based therapy following PSE had an advantage in the maintenance of higher platelet counts, and PSE possibly caused an increase in adherence to PEG-IFN. Although patients with genotype 2 might be better candidates for PSE, further evaluation is needed. Careful follow-up of PSE-treated patients, even though they may have achieved an SVR, is needed to detect HCC.
Journal of Gastroenterology 05/2011; 46(8):1010-9. · 4.16 Impact Factor
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ABSTRACT: The effect of transforming growth factor (TGF)-α on fibrosis varies between cell types and the role of TGF-α in hepatic fibrosis has not been fully elucidated.
We examined the effect of TGF-α on hepatic fibrosis using TGF-α-expressing transgenic mice fed a methionine- and choline-deficient (MCD) diet and human hepatic stellate cells (HSCs) line LX-2, rat and human primary HSCs.
Although the expression levels of the tissue inhibitor of metalloproteinases-1 and α1(I) collagen mRNA were unchanged, feeding the TGF-α transgenic mice the MCD diet resulted in greater expression of the murine functional analogue of matrix metalloproteinase-1 (MMP-1), MMP-13 mRNA and protein and attenuated hepatic fibrosis compared with wild-type mice. TGF-α overexpression did not affect the extent of the steatosis, oxidative stress and hepatic inflammation in the MCD diet-fed mice. The effect of TGF-α on the fibrogenic and anti-fibrogenic gene expressions varied between cell types in vitro. TGF-α increased MMP-1 mRNA expressions that were completely blocked by gefitinib in LX-2 cells. The extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase and p38 pathways were involved in MMP-1 mRNA expression in LX-2 cells. Although TGF-α increased the phosphorylation of p38, the p38 inhibitor activated the RAS-ERK pathway and increased TGF-α-induced MMP-1 mRNA expression, which suggested that there may be a crosstalk between the RAS-ERK and the p38 pathways in LX-2 cells.
The TGF-α may attenuate hepatic fibrosis in part because of upregulation of the expression of MMP-1. The balance between fibrogenic and anti-fibrogenic gene expression and between the activity of the RAS-ERK and the p38 pathways may be crucial for the fibrotic process.
Liver international: official journal of the International Association for the Study of the Liver 04/2011; 31(4):572-84. · 3.82 Impact Factor
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ABSTRACT: We evaluated the respiratory effects of balloon-occluded retrograde transvenous obliteration (BRTO) performed for the treatment of gastric varices complicating liver cirrhosis.
From 2005 to 2009, we performed BRTO in 20 patients with gastric fundal varices, by intravariceal injection of 5% ethanolamine oleate (EO) as the sclerosant. We studied the effect of BRTO on the respiratory gas exchange, chest X-ray findings, computed tomography (CT) findings, pulmonary function parameters, and (99m) Tc-MAA lung perfusion scintigraphy findings. Subjects undergoing balloon-occluded retrograde transvenous varicerography (BRTV) without injection of the sclerosant served as the controls.
Arterial blood gas analysis revealed a decrease in the mean arterial partial oxygen tension (PaO(2)) (P < 0.01), and increase in the alveolar-arterial oxygen tension difference (AaDO(2)) after BRTO (P < 0.01), as compared with the results obtained before the BRTO, while breathing room air. No changes were observed after BRTV as compared with the previous findings. In addition, a significant correlation was observed between the change of the PaO(2) and the volume of the sclerosant injected (rs = 0.511, P = 0.011). Left-pleural effusion was noted on the chest CT in 20% of the patients. On pulmonary function testing, decrease of the vital capacity was noted in two of the 20 patients after BRTO.
The aforementioned results suggest that BRTO performed using EO as the sclerosant induces pulmonary function disorders. The effect was found to depend on the total amount of EO injected. Therefore, careful respiratory monitoring seems necessary in patients undergoing BRTO, particularly those in whom large volumes of the sclerosant are used.
Journal of Gastroenterology and Hepatology 03/2011; 26(9):1389-94. · 2.87 Impact Factor
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ABSTRACT: To predict which chronic hepatitis C patients are likely to be late-responders, we herein investigated the clinical characteristics of null-responders at 36 wk with hepatitis C virus (HCV) genotype Ib and a high viral load during the course of pegylated interferon (Peg-IFN)/ribavirin therapy.
One hundred forty-two patients with genotype Ib HCV and a high viral load were included in this study. Peg-IFNα2b (1.5 μg/kg once a week) and ribavirin (600-1000 mg per day according to body weight) were administered for 48 wk. We defined null-responders as the cases that never cleared serum HCV RNA as determined using RT-PCR until 36 wk. Other patients were defined as responders. We compared the clinical characteristics (age, gender, body mass index, previous treatment) and HCV RNA titer during the therapy between null-responders and responders.
The HCV RNA clearance rate was 17.9% (24/134), 46.3% (62/134), 60.6% (86/142), 86.6% (123/142), and 88.0% (125/142) at 4, 8, 12, 24, and 36 wk, respectively. There were 17 patients (12.0%) who were still null-responders at 36 wk. There were no differences in the clinical characteristics between the responders and null-responders except for the titer and decline rates of HCV RNA at 1 wk and 4 wk. The HCV RNA titers at 1 wk and after 4 wk of treatment were significantly higher in the null-responders in comparison to the responders (P <0.01). The serum HCV RNA titers of the responders decreased by 1.3 log after 1 wk of treatment, and 1.6 log after 4 wk of treatment, respectively. On the other hand, the titers of the null responders decreased by only 0.5 log after 1 wk, and 0.7 log after 4 wk of treatment, respectively. The decrease rates of HCV RNA after 1 and 4 wk of treatment were significantly worse for null responders than for the responders (P <0.01).
The HCV RNA titer at 1 wk and 4 wk after initiating treatment may be useful for predicting null-responders to Peg-IFNα2b/ribavirin therapy. However, further investigation is needed to determine the optimal time at which the decision to discontinue the Peg-IFNα2b/ribavirin therapy for null-responders can be made.
World journal of hepatology. 11/2010; 2(11):401-5.
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ABSTRACT: Bleeding from ectopic varices, including duodenal varices, is uncommon, but it can be difficult to manage. The clinical data of patients diagnosed and treated for duodenal varices were reviewed to investigate the strategy for treatment.
The present study reviewed the clinical data of 10 patients with duodenal varices (mean age, 58.2 ± 15.6 years) at our associated institutes during the period between January 1996 and December 2008.
Nine patients had duodenal varices located in the second portion, whereas in one case they were located in the duodenal bulbus. The underlying diseases included liver cirrhosis in eight patients, and extrahepatic portal vein obstruction in two patients. The lesions were identified with bleeding from varices in eight of 10 patients. Initial hemostasis was achieved in all eight patients. However, among four patients treated endoscopically only, two patients died from rebleeding from varices and two died from hepatic failure resulting from variceal bleeding. Additional interventional radiology (IVR) was used in three patients and additional surgery was carried out in one case. One patient who was treated with balloon-occluded retrograde transvenous obliteration rebled during IVR and died from bleeding. Two patients who underwent double balloon-occluded embolotherapy and one case who had surgery achieved good clinical outcomes.
Although endoscopic treatment is useful for initial hemostasis of hemorrhagic duodenal varices, the patients who underwent additional IVR after endoscopic treatment achieved good outcomes.
Digestive Endoscopy 10/2010; 22(4):275-81. · 1.19 Impact Factor
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ABSTRACT: Primary biliary cirrhosis (PBC) is regarded as an autoimmune liver disease and familial clustering of PBC could represent some genetic predisposition to the disease.
To elucidate the genetic background of PBC by investigating familial cases of PBC.
Familial cases were picked out from 171 PBC patients who enrolled in this study. We analyzed them and their family members, and compared them clinically and immunogenetically to non-familial cases.
Out of 171 PBC patients, ten (5.8%) were identified as familial PBC in five families. The clinical features of familial PBC were almost comparable to those of non-familial PBC. The distribution of human leukocyte antigens (HLA)-A, -B and -DR in familial PBC showed no specificity. Two new PBC patients were identified in one family in addition to the two originally enrolled PBC patients, resulting in four patients with PBC within the same family. The two new PBC patients had an identical HLA haplotype. On the other hand, one HLA-identical sister of a PBC patient in another family did not develop PBC.
Primary biliary cirrhosis can exhibit familial clustering without any HLA predisposition, however, a survey of families for PBC could be useful for identifying new patients with PBC in the asymptomatic stage for earlier diagnosis and treatment.
Digestive Diseases and Sciences 12/2009; 55(9):2651-8. · 2.12 Impact Factor
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ABSTRACT: We recently encountered a case of autoimmune hepatitis whose symptoms worsened after switching from a brand name to a generic version of prednisolone. The patient was a 46-year-old woman. She was admitted because of elevation of alanine aminotransferase (ALT) levels during follow-up sessions. We diagnosed worsening of autoimmune hepatitis and increased the medication dose of prednisolone, which resulted in a quick normalization of serum ALT levels. When the prednisolone medication was switched from a brand name to a generic version, the serum ALT levels again increased. We concluded that switching from a brand name to generic version of the drug was one of reasons for the elevation in the serum ALT levels. Although most generic drugs are considered to be useful, it is important to carefully observe patients to confirm that an equivalent effect is obtained after switching from a brand name to a generic drug.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 10/2009; 106(10):1488-93.
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ABSTRACT: Apoptosis via the Fas/Fas ligand signalling system plays an important role in the development of various liver diseases. The administration of an agonistic anti-Fas antibody to mice causes massive hepatic apoptosis and fulminant hepatic failure. Several growth factors including hepatocyte growth factor (HGF) have been found to prevent apoptosis.
In this study, we demonstrated the overexpression of HGF to have a protective effect on Fas-mediated hepatic apoptosis using a transgenic mice (Tg mice) model.
In HGF Tg mice, the elevation of alanine aminotransferase was dramatically inhibited at 12 and 24 h after the administration of 0.15 mg/kg anti-Fas antibody. HGF Tg mice showed a significantly lower number of apoptotic hepatocytes at 12 h compared with wild-type (WT) mice. Furthermore, 85% (six of seven) HGF Tg mice were able to survive after the administration of 0.3 mg/kg anti-Fas antibody, while none of the WT mice survived. The Bcl-xL expression was increased in HGF Tg mice, while there was no difference in the expression of Bax, Bid, Mcl-1 and bcl-2 between WT mice and HGF Tg mice. In addition, the HGF Tg mice showed more Akt phosphorylation than the WT mice both before and after the anti-Fas antibody injection.
Taken together, our findings suggest that HGF protects against Fas-mediated liver apoptosis in vivo, and the upregulation of Bcl-xL via Akt activation may also play a role in the protective effects of HGF.
Liver international: official journal of the International Association for the Study of the Liver 10/2009; 29(10):1562-8. · 3.82 Impact Factor
