担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular and Clinical Oncology  

Highly sensitive Lens culinaris agglutinin-reactive fraction of α-fetoprotein (hs-AFP-L3) is a specific marker for hepatocellular carcinoma (HCC) and has been reliable in cases with a low serum α-fetoprotein (AFP) level. However, the biomarkers that contribute to hepatocarcinogenesis during the long-term observation are not yet clear. The present study reported the clinical utility of hs-AFP-L3 in the long-term observation of patients with chronic liver disease. The subjects were 106 patients with chronic liver disease without HCC or a history of HCC treatment and who had been followed for >12 months. hs-AFP-L3 was measured using cryopreserved serum. The factors contributing to hepatocarcinogenesis were examined using univariate and multivariate analyses. The median observation period was 88 months (15-132 months). The cumulative incidence of HCC was 10.5% at 5 years and 19.6% at 10 years. The univariate analysis revealed that age ≥55 years old, platelet count ≤13.1x10⁴/µl, hyaluronic acid ≥80.8 ng/ml, alanine transaminase ≥47 U/l, AFP ≥6.3 ng/ml, hs-AFP-L3 ≥3.5% and des-γ-carboxy prothrombin (DCP) ≥25 mAU/ml were significant factors. In the multivariate analysis, platelet count ≤13.1x10⁴/µl [hazard ratio (HR), 4.966; 95% confidence interval (CI), 1.597-15.437; P=0.006] and hs-AFP-L3 ≥3.5% (HR, 5.450; 95% CI, 1.522-19.512; P=0.009) were extracted as significant factors contributing to hepatocarcinogenesis. In addition, for cases with AFP <20 ng/ml, a multivariate analysis revealed that hs-AFP-L3 ≥4.9% (HR, 11.608; 95% CI, 2.422-55.629; P=0.002) and DCP ≥25 mAU/ml (HR, 3.936; 95% CI, 1.088-14.231; P=0.037) were significant factors contributing to hepatocarcinogenesis. hs-AFP-L3 is a useful marker for predicting hepatocarcinogenesis in the long-term observation of patients with chronic liver disease.

DOI： 10.3892/mco.2021.2336

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

<jats:sec><jats:title>Aim</jats:title><jats:p>Direct‐acting antiviral (DAA) therapy for hepatitis C virus is associated with high sustained virologic response rates. However, patients for whom DAA therapy fails acquire resistance‐associated substitutions (RASs). We therefore evaluated the efficacy of DAA retreatment and factors associated with retreatment failure.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Non‐structural 5A RASs were investigated at the start of DAA therapy and at treatment failure in 64 patients with hepatitis C virus genotype 1b for whom DAA combination therapy had failed. A total of 59 patients were introduced to DAA retreatment. The factors associated with retreatment failure were investigated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 20 of 43 (46.5%) daclatasvir + asunaprevir‐treated patients with virologic failure had no RASs at baseline, and three (15%) acquired P32 deletion RASs. Four of seven sofosbuvir/ledipasvir‐treated patients with virologic failure had more than two RASs of NS5A at baseline. The sustained virologic response rates on retreatment were as follows: sofosbuvir/ledipasvir, 81.8%; with elbasvir + grazoprevir, 0%; and glecaprevir/pibrentasvir, 87.5%. Patients for whom sofosbuvir/ledipasvir or elbasvir + grazoprevir failed achieved sustained virologic response with glecaprevir/pibrentasvir. Two of three patients for whom glecaprevir/pibrentasvir retreatment failed had Q24/L28/R30 and A92K RASs; the other had P32 deletion RAS at baseline. Interestingly, 10 of 11 patients with retreatment failure had the <jats:italic>interleukin (IL)‐28B</jats:italic> single‐nucleotide polymorphism (SNP) minor allele. A multivariate analysis showed that the <jats:italic>IL28B</jats:italic> SNP minor allele (<jats:italic>P</jats:italic> = 0.005, odds ratio 28.291) was an independent risk factor for retreatment failure.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In addition to viral factors (e.g. Q24, L28, R30, and A92 or P32 deletion RASs), host factors (e.g. <jats:italic>IL28B</jats:italic> SNP) are associated with DAA retreatment failure.</jats:p></jats:sec>

DOI： 10.1111/hepr.13474

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CiNii Research

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Plos One  

Background and aims Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) exert high anti-HCV activity and are expected to show anti-inflammatory effects associated with HCV elimination. Furthermore, hepatocellular carcinoma (HCC) is known to dedifferentiate from hypovascular tumors, such as dysplastic nodules or well-differentiated HCC, to hypervascular tumors. We therefore explored whether or not DAAs can suppress the growth and hypervascularization of hypovascular tumors. Methods We enrolled 481 patients with HCV genotype 1 infection who were treated with Daclatasvir and Asunaprevir therapy. Of these, 29 patients had 33 hypovascular tumors, which were confirmed by contrast-enhanced MRI or CT before therapy. We prospectively analyzed the cumulative incidence of HCC, i.e. the growth or hypervascularization of hypovascular tumors, and compared the HCC development rates between patients with hypovascular tumors and those without any tumors. Results The mean size of the hypovascular tumors was 11.3 mm. Twenty seven of 29 patients who achieved an SVR had 31 nodules, 19 of 31 nodules (61.3%) showed tumor growth or hypervascularization, and 12 (38.7%) nodules showed no change or improvement. The cumulative incidence rates of tumor growth or hypervascularization were 19.4% at 1 year, 36.0% at 2 years, 56.6% at 3 years, and 65.3% at 4 years. Among the patients who achieved a sustained virologic response, the cumulative HCC development rates of patients with hypovascular tumors was significantly higher than in those without any tumors. A Cox proportional hazard analysis showed that a history of HCC therapy, the presence of a hypovascular tumor, and AFP >4.6 ng/mL at the end of treatment were independent risk factors for HCC development. Conclusion Hypovascular tumors developed into HCC at a high rate despite the elimination of HCV by DAAs. As patients with hypovascular tumors were shown to have a high risk of HCC development, they should undergo strict HCC surveillance. Copyright:

DOI： 10.1371/journal.pone.0237475

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medicine  

Nonalcoholic fatty liver disease (NAFLD) is recognized as a hepatic manifestation of metabolic syndrome because of the association with visceral obesity. However, the association between NAFLD and subcutaneous fat accumulation remains unclear.The study population included 3197 participants in regular health checkups, who were both hepatitis B virus surface antigen and hepatitis C virus antibody-negative, and consumed <20 g of alcohol per day. They were divided according to 4 quantiles of subcutaneous fat area (SFA) and visceral fat area (VFA) on computed tomography. Fatty liver was diagnosed using ultrasonography (FL-US).The prevalence of FL-US increased across the SFA categories, even after adjusting for the VFA, in both men (P < .001) and women (P < .001). This significant association between FL-US and the SFA was already detected from the second SFA quantile. It is noteworthy that the mean body mass index (BMI) of the subjects in the second quantile was 23.7 kg/m in men and 22.6 kg/m in women. Independent positive associations were observed between alanine aminotransferase elevation, and both the SFA and VFA in men, while gamma glutamyl transpeptidase elevation was independently associated with the VFA, but not the SFA, in both men and women. Similarly, the components of metabolic syndrome were independently associated with the VFA, but were less strongly associated (or not associated at all) with the SFA.This cross-sectional study suggests that NAFLD is independently associated with both visceral and subcutaneous adiposity ab initio, which is a characteristic that distinguishes NAFLD from other components of metabolic syndrome.

DOI： 10.1097/MD.0000000000017879

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PubMed

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

<jats:p>A 68‐year‐old Japanese man with decompensated cirrhosis due to hepatitis C virus (HCV) genotype 1b infection was treated with sofosbuvir (SOF; 400 mg/day), ledipasvir (LDV; 90 mg/day), and ribavirin (RBV; 400 mg/day). Before treatment, his Child–Pugh and Model for End‐Stage Liver Disease (MELD) scores were 10 (class C) and 13 points, respectively. Although RBV was initially given at two‐thirds the normal dose due to anemia, his hemoglobin level gradually declined, and RBV was reduced to 200 mg daily on day 11, and 200 mg every other day on day 14. His alanine aminotransferase level gradually decreased during combination therapy; and HCV‐RNA was undetectable on day 28. He complained of fatigue from day 49, and RBV was ceased. On day 56, he asked to discontinue treatment because of strong fatigue and insomnia. As hepatic encephalopathy occurred just after the cessation of direct‐acting antivirals, diuretics were discontinued, and treatment with synthetic disaccharides and intractable antibiotics were given, after which his consciousness returned to normal. Ascites gradually disappeared, and a sustained virologic response (SVR) was achieved. At 1.5 years after treatment, his Child–Pugh and MELD scores had improved to 6 (class A) and 10 points, respectively. Although he did not experience hepatic encephalopathy during the observation period, his blood ammonia concentration persistently increased. We reported a case of decompensated cirrhosis in a patient who achieved SVR with SOF/LDV plus RBV for 8 weeks. Although his liver function improved after treatment, careful long‐term observation is required for complications of liver cirrhosis, even after HCV elimination.</jats:p>

DOI： 10.1111/hepr.13235

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CiNii Research

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

Background: Acute liver failure is a potentially fatal disease of various etiologies for which liver transplantation is the only known curative treatment. Although the decision-making on transplantation is largely dependent on the severity of liver injury (based on predicting a fatal outcome), a statistical analysis to predict “survival” has not been extensively conducted. In this study, we investigate the medical history of patients in two distinct areas of Japan with the aim of identifying the predictors of survival in patients with acute liver injury (ALI). Methods: Datasets of 301 patients with ALI in two distinct areas (93 in southern Kyushu and 208 in northern Tohoku) of Japan, who were treated from 2004 to 2014, were included in the analysis. Results: Among the enrolled 301 cases, 263 patients survived without transplantation. A PT-INR of ≥ 1.3 during the clinical course was found to be adequate for predicting a poor prognosis, because all of the fatal cases emerged from this population (hazard ratios: southern Kyushu, 0.2827; northern Tohoku, 0.1862). All surviving patients showed a reduction in their PT-INR during treatment, whereas the PT-INR did not decrease in the patients with a poor prognosis. A PT-INR of < 1.3 on days 7 and 8 efficiently predicted transplant-free survival (log-rank test: southern Kyushu, P = 0.0030; northern Tohoku, P = 0.0022). Conclusions: A PT-INR of ≥ 1.3 during the clinical course might identify cases with a poor prognosis, while the recovery of the PT-INR to < 1.3 predicts transplant-free survival.

DOI： 10.1007/s00535-017-1421-3

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Plos One  

Objective The present study aimed to reveal the factors associated with virologic failure in sofosbuvir and ledipasvir (SOF/LDV)-treated patients, and identify baseline NS5A or NS5B resistance-associated substitutions (RASs). Methods Four hundred ninety-three patients with Hepatitis C Virus (HCV) genotype 1b infection were treated with SOF/LDV; 31 had a history of interferon (IFN)-free treatment with daclatasvir and asunaprevir. The effect of baseline RASs on the response to SOF/LDV therapy was analyzed. Results Overall, a sustained virologic response at 12 weeks (SVR12) was achieved in 476 patients (96.6%). The SVR12 rates in the patients with IFN-free treatment-naïve and retreatment were 97.6% and 80.6%, respectively. HCV elimination was not achieved in 17 patients, 11 (including 5 with IFN-free retreatment) of whom had virologic failure. Eight patients had coexisting NS5A RASs of Q24, L28 and/or R30, L31, or Y93 and one patient had coexisting NS5A RASs of P32L and A92K. Interestingly, 10 and 8 patients had NS5B A218S and C316N RAS respectively. According to a multivariate analysis, coexisting NS5A RASs, NS5A P32 RAS, NS5B A218 and/or C316 RASs, and γ-glutamyltranspeptidase were associated with virologic failure. In the naïve patients, all patients without NS5B A218 and/or C316 RAS achieved an SVR12. Notably, the SVR12 rates of patients with coexisting NS5A and NS5B RASs were significantly lower (83.3%). Conclusions Although SOF/LDV therapy resulted in a high SVR12 rate, coexisting NS5A and NS5B RASs were associated with virologic failure. These results might indicate that the coexisting baseline RASs influence the therapeutic effects of SOF/LDV.

DOI： 10.1371/journal.pone.0198642

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

Background: Daclatasvir (DCV) and asunaprevir (ASV) combination therapy has been primarily used in patients without NS5A L31 or Y93 resistance-associated substitutions (RASs) before treatment. We examined the characteristics of patients without these baseline RASs who did not achieve hepatitis C virus eradication with DCV and ASV combination therapy and identified new baseline NS5A RASs that are closely associated with failure of combination therapy. Methods: Three hundred thirty-five patients with hepatitis C virus genotype 1 infection with no NS5A L31, NS5A Y93, and NS3 D168 RASs before DCV and ASV combination therapy and no history of protease inhibitor therapy were enrolled. All RASs were evaluated by direct sequencing. Results: Sustained virologic response at 12 weeks (SVR12) was achieved in 297 patients (89%). Patients with NS5A Q24, L28, and/or R30 RASs or concomitant NS5A F37 and Q54 RASs had a significantly lower SVR12 rate than patients without these RASs (70% vs 92%, p < 0.001 and 79% vs 92%, p = 0.002 respectively). Multivariate analysis showed that NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs were significantly associated with virologic failure. The SVR12 rate in patients without NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs was 96.2% (202/210). Conclusions: In patients without NS5A L31 or Y93 RASs, the presence of NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs at the baseline was associated with failure of DCV and ASV combination therapy. The coexistence of baseline RASs other than NS5A L31 and Y93 may affect the therapeutic effectiveness of DCV and ASV combination therapy.

DOI： 10.1007/s00535-016-1303-0

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

We report a female patient with acute hepatitis B due to horizontal transmission of hepatitis B virus from her husband, who suffered from de novo hepatitis B. A 48-year-old man underwent peripheral blood stem cell transplantation (PBSCT) for adult T-cell leukemia/lymphoma. Nine months after the initial treatment, he was referred to our hospital because of jaundice. Laboratory data showed elevated serum aminotransferase levels and hepatitis B surface antigen (HBsAg) positivity. We diagnosed de novo hepatitis B because a pre-PBSCT serum sample was negative for HBsAg and positive for anti-hepatitis B core antibody (HBcAb). His liver function improved with entecavir therapy. Two months after his diagnosis of hepatitis B, his 31-year-old wife was admitted with fever and appetite loss. She was diagnosed with acute hepatitis B because of increased serum aminotransferase levels and HBsAg and immunoglobulin M HBcAb positivity. Sequencing of HBV DNA in the serum obtained from both patients showed 99.9% homology. Therefore, we diagnosed her acute hepatitis B as due to horizontal transmission of de novo hepatitis B from her husband. HBV derived from de novo hepatitis B should be considered a potential source of infection, although intrafamilial transmission of de novo hepatitis B is rare.

DOI： 10.1111/hepr.12422

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Plos One  

Background: It has been hypothesized that persistent hepatitis C virus (HCV) infection is mediated in part by viral proteins that abrogate the host immune response, including the complement system, but the precise mechanisms are not well understood. We investigated whether HCV proteins are involved in the fragmentation of complement component 4 (C4), composed of subunits C4α, C4β, and C4γ, and the role of HCV proteins in complement activation. Methods: Human C4 was incubated with HCV nonstructural (NS) 3/4A protease, core, or NS5. Samples were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then subjected to peptide sequencing. The activity of the classical complement pathway was examined using an erythrocyte hemolysis assay. The cleavage pattern of C4 in NS3/4A-expressing and HCV-infected cells, respectively, was also examined. Results: HCV NS3/4A protease cleaved C4γ in a concentration-dependent manner, but viral core and NS5 did not. A specific inhibitor of NS3/4A protease reduced C4γ cleavage. NS3/4A protease-mediated cleavage of C4 inhibited classical pathway activation, which was abrogated by a NS3/4A protease inhibitor. In addition, co-transfection of cells with C4 and wild-type NS3/4A, but not a catalytic-site mutant of NS3/4A, produced cleaved C4γ fragments. Such C4 processing, with a concomitant reduction in levels of full-length C4γ, was also observed in HCV-infected cells expressing C4. Conclusions: C4 is a novel cellular substrate of the HCV NS3/4A protease. Understanding disturbances in the complement system mediated by NS3/4A protease may provide new insights into the mechanisms underlying persistent HCV infection. © 2013 Mawatari et al.

DOI： 10.1371/journal.pone.0082094

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Aim: The prognostic value of serum C-X-C motif chemokine ligand 10 (CXCL10) levels for liver function was investigated in hepatitis C virus (HCV)–infected patients with compensated or decompensated cirrhosis (cLC and dLC, respectively) following treatment with direct-acting antivirals (DAAs). Methods: In this nationwide study involving multiple centers, 164 HCV-related liver cirrhosis patients (95 with cLC and 69 with dLC), who underwent treatment with DAAs, were analyzed. Serum levels of CXCL10 were assessed at the baseline (pre-CXCL10) and at 12 or 24 weeks after the end of therapy (post-CXCL10). Associations between CXCL10 levels and liver function after DAA therapy were evaluated. Results: Of the 164 study patients, the albumin–bilirubin (ALBI) grade was reduced to Grade 1 in 85 patients at one year after end of therapy (EOT1Y). Serum CXCL10 ratios (post-CXCL10/pre-CXCL10 levels) were significantly lower in ALBI Grade 1 patients than the others (p = 0.014) at EOT1Y. Receiver operating curve analysis for distinguishing ALBI Grade 1 at EOT1Y demonstrated that the area under the curve was 0.611, with an optimal cutoff value of 0.504. Multivariate analysis revealed that body mass index (BMI; odds ratio [OR] 0.816; p < 0.001), absence of ascites (OR 3.340; p = 0.003), FIB-4 index (OR 0.872; p = 0.026), and serum CXCL10 ratios < 0.504 (OR 2.630; p = 0.010) were independently correlated to ALBI Grade 1 at EOT1Y. Conclusions: The post-to pretreatment serum CXCL10 ratio was independently associated with short-term liver function outcome following HCV eradication in cirrhotic patients. Registry and registration Nos: This study was registered to the University Hospital Medical Information Network (36,150).

DOI： 10.1111/hepr.70139

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Background and Aims: Although direct-acting antivirals (DAAs) achieve high sustained virologic response (SVR) rates, the long-term outcomes of patients with hepatitis C virus (HCV)-related cirrhosis remain variable. Growth differentiation factor 15 (GDF15), a stress-induced cytokine, has emerged as a potential biomarker for liver disease progression. This study aimed to evaluate the prognostic value of serum GDF15 levels in predicting hepatocellular carcinoma (HCC), hepatic decompensation, and mortality in patients with HCV-related cirrhosis. Methods: We retrospectively analyzed 196 patients with HCV-related cirrhosis who achieved SVR at 18 Japanese institutions. Serum GDF15 levels were measured at baseline (BL) and 24 weeks posttreatment (p24w). A previously validated cutoff of 1.75 ng/mL was applied. The clinical outcomes included HCC occurrence, hepatic decompensation, and all-cause mortality. Results: During a median follow-up of 46.2 months, 75 patients developed HCC, 28 experienced hepatic decompensation, and 25 died. Hepatic decompensation occurred significantly less frequently in the BL GDF15-low group. Importantly, no deaths occurred in the GDF15-low group, whereas the 5-year survival rate in the GDF15-high group was 71.7%. Similar trends were observed for GDF15 levels at p24w. In the overall cohort, GDF15 was not significantly associated with incident HCC; among HCC-naïve patients, a nonsignificant trend toward lower 3-year HCC incidence was observed in the GDF15-low group. Conclusions: Serum GDF15 is a promising prognostic biomarker for post-SVR outcomes in patients with HCV-related cirrhosis. Its ability to predict decompensation and mortality through a validated cutoff supports its use for risk stratification and long-term management in patients with chronic liver disease.

DOI： 10.1111/hepr.70041

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology and Hepatology Australia  

Background and Aim: This study aimed to compare the therapeutic effects and safety of lenvatinib (LEN) plus transcatheter arterial chemoembolization (LEN-TACE) and atezolizumab plus bevacizumab (Atez/Bev) as the first-line therapies in patients with intermediate-stage hepatocellular carcinoma (HCC) beyond the up-to-seven criteria. Methods: We enrolled 768 patients with HCC treated with first-line systemic therapy, and 154 patients were enrolled and categorized into either the LEN-TACE therapy (n = 42) or Atez/Bev (n = 112) groups. After propensity score matching (PSM), 72 patients (LEN-TACE group, n = 36; Atez/Bev group, n = 36) were analyzed. Results: After PSM, the median progression-free survival showed no significant differences between the LEN-TACE and Atez/Bev groups (8.5 [95% confidence interval (CI): 6.1–10.7] months vs. 8.6 (95% CI: 5.3–12.1) months, respectively; p = 0.973). Regarding median overall survival (OS), no significant differences were noted between the LEN-TACE and Atez/Bev groups (37.3 [95% CI: 31.2–60.2] months vs. 32.4 (95% CI: 19.5–NE) months, respectively; p = 0.183). Regarding adverse events (AEs) of grade ≥ 3, no significant difference was observed between the two groups. Multivariate analysis revealed that the ALBI grade 1 and low AFP levels were independent factors for OS. Conclusion: LEN-TACE therapy may be one of the effective treatment strategies in intermediate-stage HCC patients beyond the up-to-seven criteria.

DOI： 10.1111/jgh.17024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

Aim: We investigated the usefulness of serum CXCL10 levels for predicting prognosis in hepatitis C virus (HCV)-infected patients with compensated and decompensated cirrhosis (cLC and dLC) after direct-acting antiviral (DAA) therapy. Methods: This nationwide multicenter study enrolled 212 HCV-associated LC patients, consisting of 113 cLC and 99 dLC patients, receiving DAA therapy, who had preserved serum samples. Serum CXCL10 levels were measured at pretreatment (pre-CXCL10) and posttreatment (12 or 24 weeks after the end of treatment: EOT12W or EOT24W) (post-CXCL10). We evaluated the relationship between these levels and liver transplantation (LT)-free overall survival (OS) and clinical outcomes. Results: During the observational period (median: 37 months), 27 patients developed dLC events and 20 died. The post-CXCL10 levels were significantly higher in dLC than in cLC (P = 0.006) and among patients who died than those who survived (P < 0.001). The cutoff value of serum post-CXCL10 level for discriminating the occurrence of death (345 pg/mL) could predict LT-free OS in groups of all, cLC, and dLC patients (P < 0.001, P = 0.007, and P < 0.001, respectively). Multivariate analysis on factors associated with LT-free OS demonstrated that age (HR 1.076; P = 0.013), Child–Pugh score at EOT12W (HR 1.575; P = 0.009), and serum post-CXCL10 level (HR 1.003; P = 0.001) were independent factors. Conclusions: The serum post-CXCL10 level was independently related to survival in HCV-associated LC patients.

DOI： 10.1007/s00535-025-02282-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

Background: Direct-acting-antivirals (DAAs) achieve high sustained-virologic response (SVR) rates, even in patients with hepatitis C virus (HCV)-related decompensated liver cirrhosis (LC). However, predictors of post-treatment liver function improvement and survival remain unclear. This study evaluated pretreatment angiopoietin-2 (Ang2) levels as a predictor of prognosis and liver functional reserve after DAA treatment. Methods: This multicenter retrospective study included 123 patients with HCV-related decompensated LC treated with sofosbuvir/velpatasvir. Serum Ang2 levels were quantified, and liver function was assessed using the Child–Pugh grading at baseline and 12 weeks after the end of treatment (SVR12). Factors associated with prognosis and post-SVR liver functional reserve (Child–Pugh grade C) were investigated. Results: Multivariate Cox regression analysis revealed that, in addition to age and creatinine levels at SVR12, baseline Ang2 levels (hazard ratio [HR] = 1.151 per 1000 pg/mL, P = 0.033) and Child–Pugh grade C at SVR12 (HR = 11.765, P < 0.001), but not baseline Child–Pugh grade C, were significantly associated with the overall survival. Multivariate analysis revealed that baseline Ang2 levels and baseline Child–Pugh grade C were significantly and independently associated with Child–Pugh grade C at SVR12. The combination of elevated baseline Ang2 levels (≥ 8684 pg/mL; 1 point) and baseline Child–Pugh grade C (1 point) effectively stratified patients with a high likelihood of having Child–Pugh Grade C at SVR12. The incidence rates were as follows: 0 points, 2.1% (2/96); 1 point, 37.5% (9/24); and 2 points, 100% (2/2) (P < 0.001). Conclusions: Pretreatment Ang2 levels predict survival and liver functional reserve after SVR in HCV-related decompensated LC.

DOI： 10.1007/s00535-025-02275-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Aim: Liver cirrhosis is a severe condition that often progresses to the decompensated phase, highlighting the global urgency for the development of antifibrotic agents. Hepatocyte growth factor (HGF) strongly promotes liver regeneration and attenuates fibrosis. However, HGF has not been clinically applied to treat patients with liver cirrhosis. Here, we aimed to explore the antifibrotic effects and mechanism(s) of action of HGF, through continuous intravenous infusions, in rats with bile duct ligation (BDL). Methods: Sprague–Dawley rats were subjected to BDL. Two weeks post-BDL, an intravenous catheter was inserted into the right jugular vein. After 1 week, the rats were randomized into different groups for continuous intravenous infusion of phosphate-buffered saline alone, HGF at 0.25 mg/kg/day, or HGF at 1.0 mg/kg/day. After 10 days of treatment, the rats were euthanized, and blood and liver tissues were collected for analysis. Results: Continuous intravenous HGF infusion increased the serum albumin levels, decreased the alanine aminotransferase levels, preserved prothrombin time activity, ameliorated liver fibrosis and fibrosis-associated stellate cell activation, and significantly promoted hepatocyte proliferation in rats with BDL. HGF-MET signaling suppressed IL-6 expression and promoted matrix metallopeptidase 2 (MMP-2) expression in infiltrating macrophages in vivo and in human macrophage and hepatic stellate cell lines in vitro. Conclusion: Continuous intravenous infusion of HGF attenuated BDL-induced liver fibrosis by decreasing IL-6 expression, increasing MMP-2 expression in macrophages and hepatic stellate cells, and inactivating hepatic stellate cells directly or indirectly. These findings offer valuable insights into developing novel HGF-based therapies for liver cirrhosis.

DOI： 10.1111/hepr.14227

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般財団法人 日本消化器病学会  

<p>症例は65歳女性．肝動脈化学塞栓療法不応の肝細胞癌に対し，20XX年2月Y日アテゾリズマブ＋ベバシズマブ併用療法を導入された．Y＋15日には呼吸困難感と低酸素血症を認め，前医入院．Y＋16日に甲状腺中毒症にともなううっ血性心不全にて当院転院となった．甲状腺中毒症はヨウ化カリウム内服で改善し，Y＋40日に自宅退院となった．臨床試験ではCTCAE Grade 3以上の甲状腺機能障害は0.3%と極めてまれであり，報告する．</p>

DOI： 10.11405/nisshoshi.122.359

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CiNii Research

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一財)日本消化器病学会  

症例は65歳女性.肝動脈化学塞栓療法不応の肝細胞癌に対し,20XX年2月Y日アテゾリズマブ+ベバシズマブ併用療法を導入された.Y+15日には呼吸困難感と低酸素血症を認め,前医入院.Y+16日に甲状腺中毒症にともなううっ血性心不全にて当院転院となった.甲状腺中毒症はヨウ化カリウム内服で改善し,Y+40日に自宅退院となった.臨床試験ではCTCAE Grade 3以上の甲状腺機能障害は0.3%と極めてまれであり,報告する.(著者抄録)

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hypertension Research  

Lenvatinib is a tyrosine kinase inhibitor that effectively inhibits vascular endothelial growth factor signaling and is used for treating hepatocellular carcinoma. However, angiogenesis inhibitors often cause hypertension. Although lenvatinib-induced hypertension has been proposed as a potential surrogate marker for better prognosis, studies on blood pressure elevations and outcomes following lenvatinib initiation are limited. This study included 67 patients who underwent lenvatinib therapy at the Department of Gastroenterology, Kagoshima University Hospital, between May 2018 and December 2023. The median age of the cohort was 71 years, and 82.1% of the patients were male. The median blood pressure at admission was 128/73 mmHg, which significantly increased to 136/76 mmHg the day after lenvatinib administration. Grade 3 hypertension (≥160/100 mmHg) occurred in 37.3% of patients during hospitalization. The median increase in systolic blood pressure from admission to its peak during hospitalization was 26 mmHg. Patients who experienced an increase in blood pressure of ≥26 mmHg were classified into the blood pressure elevation group, which showed a significantly lower mortality rate than that of the blood pressure non-elevation group (35.3% vs. 81.8%, log-rank p = 0.007), even after adjusting for age, sex, disease stage, performance status, and liver reserve function. This study demonstrated that patients who experienced earlier blood pressure elevation after lenvatinib administration had lower overall mortality rates. These findings suggest that blood pressure elevations after lenvatinib initiation may serve as valuable prognostic indicators in patients with cancer undergoing lenvatinib therapy. (Figure presented.)

DOI： 10.1038/s41440-025-02149-4

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本内分泌学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本門脈圧亢進症学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.7759/cureus.57800

PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Esophagus  

Background: The rate of metachronous recurrence after endoscopic submucosal dissection for early-stage esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma is as high (10–15%). The acetaldehyde breath test may detect acetaldehyde dehydrogenase 2 gene polymorphisms. Therefore, we evaluated its usefulness in assessing metachronous recurrence in patients with esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma. Methods: A total of 76 patients underwent endoscopic submucosal dissection for esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma and were followed up for at least 3 years (non-recurrence group: 52 patients; recurrence group: 24 patients). The risk factors for carcinogenesis were compared between the recurrence and non-recurrence groups, and the acetaldehyde-to-ethanol ratio was assessed. The cutoff acetaldehyde-to-ethanol ratio that correlated with recurrence was established, and the cumulative recurrence rate was evaluated. Results: The recurrence group had a higher acetaldehyde-to-ethanol ratio, daily alcohol consumption, and Lugol-voiding lesion grade than the non-recurrence group in the univariate analysis. The cutoff acetaldehyde-to-ethanol ratio for recurrence was 28.1 based on the receiver operating characteristic curve. The multivariate analysis revealed an acetaldehyde-to-ethanol ratio of > 28.1 and a Lugol-voiding lesion grade associated with carcinogenesis. Patients with an acetaldehyde-to-ethanol ratio of ≥ 28.1 had a significantly high recurrence rate using the Kaplan–Meier method. Conclusions: The acetaldehyde-to-ethanol ratio detected using the acetaldehyde breath test could be a novel biomarker of metachronous recurrence after endoscopic submucosal dissection in patients with esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma. Trial registration number: UMIN000040615.

DOI： 10.1007/s10388-023-01024-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct‐acting antiviral (DAA) therapy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We enrolled patients with chronic hepatitis C who underwent direct‐acting antiviral therapy and achieved sustained virologic response at 12 weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow up when the absence of HCC was confirmed. Uni‐ and multivariate Cox proportional hazards models were used to identify factors contributing to HCC development, including gadoxetic acid‐enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan–Meier method, and differences between groups were assessed using the log‐rank test.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The final study cohort comprised 482 patients (median age 70.5 years; 242 men). The median follow‐up period was 36.8 months. Among 482 patients, 96 developed HCC (19.9%). The 1‐, 3‐, and 5‐year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were independent risk factors significantly associated with HCC development (<jats:italic>p</jats:italic> < 0.001–0.04). The highest risk group included patients with both a history of HCC and the presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement (the 1‐ and 3‐year cumulative HCC development rates were 14.2% and 62.2%, respectively).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>History of HCC and presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were strong risk factors for HCC development following direct‐acting antiviral therapy.</jats:p></jats:sec>

DOI： 10.1111/hepr.13964

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：大道学館出版部  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Internal Medicine  

We treated a case of gastroesophageal varices due to decompensated liver cirrhosis associated with Wilson's disease. The varicose veins penetrated the paraesophageal vein. We performed endoscopic variceal ligation (EVL) on the perforating vein and endoscopic injection sclerotherapy distally. However, 5 days after treatment, the patient vomited blood. Esophagogastroduodenoscopy showed bleeding from the ulcer after EVL at the perforating vein. We performed EVL and stopped the bleeding. However, the next day, she vomited blood again and developed hemorrhagic shock. We were able to achieve hemostasis and save the patient's life with combination therapy consisting of percutaneous transhepatic obliteration and Sengstaken- Blakemore tube placement.

DOI： 10.2169/internalmedicine.0666-22

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Journal of Gastroenterology  

An 87-year-old man consulted a former doctor with a complaint of black stool and was admitted to hospital because of anemia and multiple gastric ulcers. The laboratory findings showed that his hepatobiliary enzyme levels and inflammatory response were elevated. Computed tomography showed hepatosplenomegaly and enlarged intra-abdominal lymph nodes. Two days later, he was transferred to our hospital due to deterioration of his liver function. Since he had low level of consciousness and his ammonia level was high, we diagnosed him with acute liver failure (ALF) with hepatic coma, and started on-line hemodiafiltration. As the cause of ALF, we suspected hepatic involvement of a hematologic tumor because of high lactate dehydrogenase and soluble interleukin-2 receptor levels and large abnormal lymphocyte-like cells in the peripheral blood. Because of his poor general condition, bone marrow and other histological examinations were difficult, and he died on the third day of hospitalization. Pathological autopsy showed marked hepatosplenomegaly and the proliferation of large abnormal lymphocyte-like cells in the bone marrow, liver, spleen, and lymph nodes. Immunostaining revealed aggressive natural killer-cell leukemia (ANKL). We herein report a rare case of the development of ALF with coma due to ANKL with a review of the relevant literature.

DOI： 10.1007/s12328-023-01771-4

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Chronic kidney disease (CKD) is a risk factor for end-stage renal disease and contributes to increased risk of cardiovascular disease morbidity and mortality. We aimed to develop a risk prediction score and equation for future CKD using health checkup data. This study included 58,423 Japanese participants aged 30–69 years, who were randomly assigned to derivation and validation cohorts at a ratio of 2:1. The predictors were anthropometric indices, life style, and blood sampling data. In derivation cohort, we performed multivariable logistic regression analysis and obtained the standardized beta coefficient of each factor that was significantly associated with new-onset CKD and assigned scores to each factor. We created a score and an equation to predict CKD after 5 years and applied them to validation cohort to assess their reproducibility. The risk score ranged 0–16, consisting of age, sex, hypertension, dyslipidemia, diabetes, hyperuricemia, and estimated glomerular filtration rate (eGFR), with area under the curve (AUC) of 0.78 for the derivation cohort and 0.79 for the validation cohort. The CKD incidence gradually and constantly increased as the score increased from ≤ 6 to ≥ 14. The equation consisted of the seven indices described above, with AUC of 0.88 for the derivation cohort and 0.89 for the validation cohort. We developed a risk score and equation to predict CKD incidence after 5 years in Japanese population under 70 years of age. These models had reasonably high predictivity, and their reproducibility was confirmed through internal validation.

DOI： 10.1038/s41598-023-32279-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Cell and Developmental Biology  

Background: Glycoprotein non-metastatic melanoma protein B (GPNMB) is expressed in macrophages during recovery from acute liver injury (ALI) in carbon tetrachloride (CCl<inf>4</inf>)-induced liver injury model mice. In this retrospective study, we assessed whether GPNMB levels in the serum and injured liver correlate with liver injury severity and prognosis in patients with ALI or acute liver failure (ALF). Methods: The study involved 56 patients with ALI or ALF who visited the Kagoshima University Hospital. Serum GPNMB level was measured over time, and the localization, proportion, origin, and phenotype of GPNMB-expressing cells in the injured liver were assessed. Finally, the phenotypes of human monocyte-derived macrophages and peripheral blood mononuclear cells (PBMCs) of patients with ALI and ALF were analyzed. Results: Peak GPNMB levels were significantly higher in patients with ALF and hepatic encephalopathy (HE), as well as in those who underwent liver transplantation or died, than in others. The peak GPNMB level correlated with prothrombin activity, prothrombin time-international normalized ratio, Model for End-stage Liver Disease score, and serum hepatocyte growth factor level. GPNMB was expressed in CD68-positive macrophages, and its level increased with the severity of liver injury. The macrophages showed the same polarization as M2c macrophages induced with interleukin-10 from human monocytes. Moreover, PBMCs from patients with ALF exhibited an immunosuppressive phenotype. Conclusion: We found that GPNMB levels in the serum and injured liver, which increased in patients with ALF, especially in those with HE, correlated with the severity of liver injury and prognosis of ALI and ALF. Moreover, GPNMB-positive macrophages exhibited the M2c phenotype. Our results indicate that persistently high GPNMB levels may be a prognostic marker in patients with ALI and ALF.

DOI： 10.3389/fcell.2023.1242152

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>We investigated whether an early‐phase prothrombin time‐international normalized ratio (PT‐INR) is an interventional prognostic indicator for patients with acute liver injury, including acute liver failure.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This was a multicenter retrospective observational study. We included 595 patients with alanine aminotransferase levels ≥300 U/L due to acute liver injury who were admitted to Kagoshima University Hospital or other collaborative investigation organizations between January 1, 2010, and December 31, 2015. Patients with alanine aminotransferase levels ≥300 U/L and no previous liver disease were defined as having an acute liver injury. Acute liver failure was defined by PT‐INR ≥1.5 with or without hepatic encephalopathy in acute liver injury patients. Data were obtained retrospectively from case reports and analyzed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The PT‐INR on day 1 was the most accurate independent prognosis predictor in patients with acute liver injury and acute liver failure. On day 1, the transplant‐free survival rates were significantly lower in patients with PT‐INR ≥1.3. The transplant‐free survival rates were also significantly higher in patients with acute liver injury and acute liver failure, in whom the PT‐INR had recovered from ≥1.3 on day 1 to <1.3 by day 8.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Early‐phase changes in the PT‐INR can predict the prognosis of patients with acute liver injury and acute liver failure. Furthermore, PT‐INR ≥1.3 could be an interventional marker, whereas PT‐INR <1.3 after 1 week could reflect prognostic improvement.</jats:p></jats:sec>

DOI： 10.1111/hepr.13848

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Targeted Oncology  

Background: A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. Objective: This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. Patients and Methods: This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. Results: After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). Conclusions: ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.

DOI： 10.1007/s11523-022-00921-x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Journal of Gastroenterology  

A 44-year-old woman presented with cough, facial edema, and progressive fatigue. Computed tomography (CT) showed an anterior mediastinal mass, and laboratory findings showed liver injury. She was diagnosed with thymoma and scheduled for thymectomy after radiation and chemotherapy. However, she was referred to our department due to exacerbation of liver injury. Autoimmune hepatitis (AIH) was suspected based on the findings of elevated anti-nuclear antibody and immunoglobulin G levels. Histological findings of a liver biopsy confirmed the diagnosis of AIH. After oral steroid therapy initiation, she had diplopia and ptosis. Five days after steroid treatment, bulbar symptoms, such as nasal voice and dysarthria, appeared. A physical examination and electrophysiological tests confirmed myasthenia gravis (MG), and to prevent MG crisis, immunoadsorption plasmapheresis and tacrolimus were started by the neurologist. MG symptoms and liver damage gradually improved, she was then treated with chemotherapy and radiation for thymoma and underwent thymectomy, now showing no relapse of AIH or MG. We report the first case of MG developing immediately after the introduction of prednisolone for AIH complicated with thymoma.

DOI： 10.1007/s12328-022-01641-5

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996–2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60–69 years, 70–79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease.

DOI： 10.1038/s41598-022-05444-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Spandidos Publications  

The prevalence of non-alcoholic fatty liver disease (NAFLD) is continuously increasing, with the proportion of patients with liver carcinogenesis due to non-alcoholic steatohepatitis (NASH) rising accordingly. Although it is important to identify individuals with hepatic carcinogenesis among patients with NAFLD, useful biomarkers have not yet been established. Previously, in a mouse model of diabetes mellitus without genetic modifications, we reported that a high-fat diet increases serine palmitoyltransferase long chain subunit 3 (SPTLC3) expression in liver tissue, accompanied by high frequency of liver carcinogenesis. Serine palmitoyltransferase (SPT) catalyzes the metabolism of fatty acids, particularly sphingolipid synthesis, and SPTLC3 has been identified as its catalytic subunit, but its role in liver disease is unclear. In the present study, the importance of SPTLC3 in NAFLD development was investigated.

DOI： 10.3892/mco.2021.2488

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Geriatric Oncology  

Objectives: Few studies have investigated factors influencing the efficacy of chemotherapy in older patients with cancer. This study aimed to evaluate the usefulness of G8, geriatric assessment (GA), and factors measured in general clinical practice for evaluating progression-free survival (PFS) of first-line palliative chemotherapy in older patients with advanced gastrointestinal cancer. Materials and methods: This was a prospective observational study of older patients (age ≥70 years) with advanced gastrointestinal cancer. The modified cut-off value of G8 was determined by referring to two or more abnormal GA conditions. The usefulness of baseline GA and G8 (conventional and modified cut-off value) was assessed according to the efficacy (PFS and disease control rate) of the administered first-line palliative chemotherapy. Results: Overall, 93 patients were evaluated between March 2017 and February 2019. A modified G8 cut-off value of ≤12 had a sensitivity and specificity of 68.9% and 46.9%, respectively. PFS was significantly prolonged in the patients with G8 > 12, serum albumin ≥3.5 g/dl, and in whom grade ≥3 adverse events occurred. There was no significant difference in the PFS between monotherapy and combination therapy. GA was not useful for predicting PFS prolongation or the occurrence of serious adverse events in first-line treatment. Conclusion: Among older patients with advanced gastrointestinal cancer who receive first-line chemotherapy, a modified G8 cut-off value of 12 points, occurrence of grade 3 or higher adverse events, albumin levels, rather than age or performance status were predictors of PFS prolongation.

DOI： 10.1016/j.jgo.2021.05.006

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology Research  

Aim: Qualitative body composition (BC) change, characterized by the combination of visceral fat gain and muscle loss, is drawing attention as a risk factor for fatty liver (FL). The present study aimed to describe trends in BC change and its association with FL in the Japanese population. Methods: Data from medical checkups carried out on 56 639 Japanese participants every 5 years from 1997 to 2017 were analyzed. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated using body mass index and body fat percentage. Subjects were divided into two groups according to deviations from the correlation line of FMI and FFMI as the reference: FMI-predominant BC and FFM-dominant BC. Fatty liver was determined using abdominal ultrasonography. Results: The prevalence of FL significantly increased from 27.3% to 42.7% in men and from 18.0% to 25.5% in women. The prevalence of FMI predominance significantly increased from 33.6% to 43.9% in men and from 29.1% to 47.0% in women. Fat mass index predominance was independently associated with FL in men and women (odds ratio: 1.96 and 1.94, respectively). Serum blood urea nitrogen level was inversely associated with FL in men and women (0.958 and 0.961, respectively) and significantly decreased from 15.8 to 14.9 mg/dl in men and from 15.1 to 14.0 mg/dl in women. Conclusions: Increasing FMI-predominant BC and decreasing serum blood urea nitrogen level could account for the increase in the prevalence of FL over 20 years. We believe that these factors stem from current lifestyle habits in Japan.

DOI： 10.1111/hepr.13631

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

<jats:sec>
<jats:title>INTRODUCTION:</jats:title>
<jats:p>
<jats:italic toggle="yes">DEFA1A3</jats:italic> encodes human neutrophil peptides (HNPs) 1–3 and has multiple copy number variations (CNVs). HNPs are associated with innate immunity. Ulcerative colitis (UC), a chronic inflammatory gastrointestinal disorder, is a life-threatening condition, and predictive markers of UC severity are needed. This study investigated the relationship between <jats:italic toggle="yes">DEFA1A3</jats:italic> CNV and UC severity.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>METHODS:</jats:title>
<jats:p>This study enrolled 165 patients with UC. The relationship between <jats:italic toggle="yes">DEFA1A3</jats:italic> CNV and disease severity was analyzed based on Mayo score, patient characteristics, and treatment methods. In addition, serum and stimulated neutrophil-derived HNP concentrations were also measured in patients with high and low <jats:italic toggle="yes">DEFA1A3</jats:italic> CNV.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESULTS:</jats:title>
<jats:p>
<jats:italic toggle="yes">DEFA1A3</jats:italic> CNV was significantly correlated with Mayo score and white blood cell count (<jats:italic toggle="yes">R</jats:italic> = 0.46, <jats:italic toggle="yes">P</jats:italic> < 0.0001; <jats:italic toggle="yes">R</jats:italic> = 0.29, <jats:italic toggle="yes">P</jats:italic> = 0.003, respectively), and only high copy numbers of <jats:italic toggle="yes">DEFA1A3</jats:italic> were independent factors for severe UC (<jats:italic toggle="yes">P</jats:italic> < 0.001, odds ratio: 1.88, 95% confidence interval, 1.34–2.61). The number of severe UC patients with high <jats:italic toggle="yes">DEFA1A3</jats:italic> CNV was significantly greater than those with low CNV. We confirmed the associations between <jats:italic toggle="yes">DEFA1A3</jats:italic> and UC severity using a validation cohort. In addition, the HNP concentration in high-copy number patients was significantly higher after neutrophil stimulation than that in low-copy number patients.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>DISCUSSION:</jats:title>
<jats:p>This study demonstrated that there is a correlation between <jats:italic toggle="yes">DEFA1A3</jats:italic> copy number and severity in patients with UC. In addition, neutrophils from UC patients with higher <jats:italic toggle="yes">DEFA1A3</jats:italic> CNV had high reactivity of secretion of HNPs after stimulation. <jats:italic toggle="yes">DEFA1A3</jats:italic> CNV may be a novel severity marker and a potential therapeutic target for UC.</jats:p>
</jats:sec>

DOI： 10.14309/ctg.0000000000000331

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CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>Rifaximin is recommended as treatment for hepatic encephalopathy (HE) that targets intestinal bacterial flora. Although combined use with synthetic disaccharides is the standard of care worldwide, the therapeutic effects of rifaximin for overt encephalopathy (OHE) in Japanese patients have not been examined sufficiently. We examined the therapeutic effects of rifaximin for OHE in Japanese patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A total of 76 patients who developed OHE of West Haven grade II or higher at least once within the 12 months before starting rifaximin were included. Blood ammonia levels and the incidence of OHE during the 12 months before and after starting rifaximin therapy were compared in a before‐and‐after study. Rifaximin efficacy and predictors of efficacy were also examined.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Post‐treatment blood ammonia levels were significantly lower than pretreatment levels. The mean annual number of OHE incidents and intravenous branched‐chain amino acid preparations used per patient were significantly lower after starting rifaximin therapy (2.51 vs. 0.76 times/year, <jats:italic>p</jats:italic> < 0.001; and 71.9 vs. 20.7 preparations/year, <jats:italic>p</jats:italic> = 0.003, respectively). The cumulative incidence of hospitalizations associated with HE significantly decreased after rifaximin therapy (hazard ratio 0.187; <jats:italic>p</jats:italic> < 0.001). The efficacy rate, defined as the proportion of patients without OHE during the administration of rifaximin for 1 year after starting rifaximin therapy, was 65.8%. Serum albumin ≥2.7 g/dl was an independent predictor of efficacy.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Rifaximin was associated with decreased blood ammonia levels, lower incidence of OHE, and fewer hospitalizations in Japanese patients with HE. In addition, serum albumin level was an important predictor on efficacy of rifaximin.</jats:p></jats:sec>

DOI： 10.1111/hepr.13622

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

Background: In hepatic cirrhosis, ascites and acute kidney injury (AKI) portend poor prognosis. We examined the incidence and characteristics of AKI in patients with hepatic ascites and the impact of diuretics on AKI onset. Methods: This study included 337 patients with hepatic ascites treated with oral diuretics during September 2013–June 2019. Incidence of AKI, cumulative survival by AKI status, and prognostic factors were investigated. Patients were divided into those treated with tolvaptan (TLV) [TLV group (n = 244)] and those not treated with TLV [control group (n = 93)]. After propensity score matching, the incidence of AKI and changes in renal function and doses of diuretics were compared. Results: The incidence of AKI overall was 35% (n = 118). Patients with AKI had a significantly worse survival than those without AKI (P = 0.001), indicating that AKI is an independent prognostic factor for hepatic ascites (P = 0.025). After adjustment for background factors in the two groups (n = 77 each), the TLV group had a significantly lower incidence of AKI (27.6% vs. 44.7%, P = 0.028). While renal function worsened with higher natriuretic agent doses in the control group, no significant change was observed in the TLV group, suggesting that TLV is an independent prognostic factor for AKI onset. Conclusions: Our study suggests that concomitant AKI significantly worsens survival in Japanese patients with hepatic ascites, and TLV and natriuretic agent combination therapy might lead to an excellent synergistic therapeutic effect of hepatic ascites and inhibition of AKI onset.

DOI： 10.1007/s00535-020-01727-2

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)日本臨床社  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般財団法人 日本消化器病学会  

<p>急性肝不全は致死的な疾患であり，肝移植以外に有効な治療法がない．急性肝不全の発症機序を知ることは新たな治療法を開発するためには不可欠である．今回われわれは急性肝不全の発症から肝再生まで中心的な役割を果たす単球，マクロファージに着目し，機序について概説する．発症から肝再生・修復までの過程は，肝細胞死の誘導，クッパー細胞の活性化，単球の肝組織への遊走・分化・増殖，炎症性マクロファージから抗炎症性マクロファージへの機能的リプログラミング，肝細胞増殖という経過で説明できる．またその過程にはさまざまな分子が関わっており，その発症機序に基づいた新規治療法が近年報告されており，今後の展開が期待される．</p>

DOI： 10.11405/nisshoshi.117.750

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CiNii Research

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一財)日本消化器病学会  

急性肝不全は致死的な疾患であり,肝移植以外に有効な治療法がない.急性肝不全の発症機序を知ることは新たな治療法を開発するためには不可欠である.今回われわれは急性肝不全の発症から肝再生まで中心的な役割を果たす単球,マクロファージに着目し,機序について概説する.発症から肝再生・修復までの過程は,肝細胞死の誘導,クッパー細胞の活性化,単球の肝組織への遊走・分化・増殖,炎症性マクロファージから抗炎症性マクロファージへの機能的リプログラミング,肝細胞増殖という経過で説明できる.またその過程にはさまざまな分子が関わっており,その発症機序に基づいた新規治療法が近年報告されており,今後の展開が期待される.(著者抄録)

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Immunology  

Backgrounds and Aims: Hepatocyte Growth Factor (HGF)-MET signaling is known to promote biological functions such as cell survival, cell motility, and cell proliferation. However, it is unknown if HGF-MET alters the macrophage phenotype. In this study, we aimed to study the effects of HGF-MET signaling on the M1 macrophage phenotype. Methods and Materials: Bone marrow-derived macrophages (BMDMs) isolated from mice were either polarized to an M1 phenotype by IFN-γ and LPS treatment or to an M2 phenotype by IL-4 treatment. Changes in M1 or M2 markers induced by HGF-MET signaling were evaluated. Mechanisms responsible for alternations in the macrophage phenotype and intracellular metabolism were analyzed. Results: c-Met was expressed especially in M1 macrophages polarized by treatment with IFN-γ and LPS. In M1 macrophages, HGF-MET signaling induced the expression of Arg-1 mRNA and secretion of IL-10 and TGF-β1 and downregulated the mRNA expression of iNOS, TNF-α, and IL-6. In addition, activation of the PI3K pathway and inactivation of NFκB were also observed in M1 macrophages treated with HGF. The increased Arg-1 expression and IL-10 secretion were abrogated by PI3K inhibition, whereas, no changes were observed in TNF-α and IL-6 expression. The inactivation of NFκB was found to be independent of the PI3K pathway. HGF-MET signaling shifted the M1 macrophages to an M2-like phenotype, mainly through PI3K-mediated induction of Arg-1 expression. Finally, HGF-MET signaling also shifted the M1 macrophage intracellular metabolism toward an M2 phenotype, especially with respect to fatty acid metabolism. Conclusion: Our results suggested that HGF treatment not only promotes regeneration in epithelial cells, but also leads to tissue repair by altering M1 macrophages to an M2-like phenotype.

DOI： 10.3389/fimmu.2020.02135

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biochemistry and Biophysics Reports  

Colorectal cancer is a multi-factorial disease involving genetic, environmental and lifestyle risk factors. In recent years, many changes in the bacterial composition of the intestinal microflora have been reported in colorectal cancer, suggesting the involvement of the intestinal microflora in the development and progression of colorectal cancer. Along with these reports, research on lactic acid bacteria that have a beneficial effect on the human body for the purpose of improving the intestinal environment and treating intestinal diseases has advanced. Among these studies, biogenics (defined as a component derived from lactic acid bacteria that acts directly on diseases regardless of the state of intestinal microflora) is a recent concept derived from the work on probiotics. Based on this concept, it is important to evaluate the effectiveness of various components derived from lactic acid bacteria in the treatment to diseases from and apply them in prevention and treatment. In this study, we investigated the antitumor effect of an extract obtained from Lactobacillus plantarum strain 06CC2 on colorectal cancer cells. In in vitro experiments, the extract derived from Lactobacillus plantarum 06CC2 significantly suppressed the proliferation of Caco2 colorectal cancer cells in comparison to control and non-cancer cells. Furthermore, we found that endoplasmic reticulum stress and the JNK/p38 MAPK signaling system are involved in the induction of apoptosis. These findings indicate the direct antitumor effect of the Lactobacillus plantarum 06CC2 extract on Caco2 colorectal cancer cells, and that this extract may have potential application as a biogenics.

DOI： 10.1016/j.bbrep.2019.100691

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(公社)日本医師会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatology International  

Background: While achieving sustained virological response (SVR) following interferon-based or direct-acting antiviral agent (DAA) treatments reduces the incidence of hepatocellular carcinoma (HCC), an increase in unexpected early occurrence or recurrence of HCC after hepatitis C virus elimination by DAA treatments has been reported. We prospectively investigated the incidence and risk factors of HCC after DAA treatment in a large multicenter cohort in Japan. Methods: Patients with chronic hepatitis C with or without cirrhosis who were treated with DAAs and obtained SVR were enrolled. DAAs were administered for 3 or 6 months. A total of 2552 patients were enrolled. Results: Of these, 70 patients (2.7%) developed HCC. The 12-, 24-, and 36-month cumulative HCC incidences were 1.3%, 2.9%, and 4.9% in all patients; 2.5%, 5.2%, and 10.0% in those with cirrhosis; and 0.9%, 2.1%, and 2.9% in those without cirrhosis, respectively. Multivariate analysis revealed age, sex, gamma-glutamyl transpeptidase level, and fibrosis-4 index to be independent factors associated with HCC. Patients with these four factors had an approximately six-to-sevenfold increased risk for HCC development. Five patients with large and early tumor occurrence did not receive contrast imaging examinations before treatment. Conclusion: Although the results of our prospective study suggested that achieving SVR by DAA treatment reduces the incidence of HCC, HCC development still occurs. Careful follow-up is important in patients with risk factors.

DOI： 10.1007/s12072-019-09939-2

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

<jats:sec><jats:title>Aim</jats:title><jats:p>Despite accumulating evidence concerning the efficacy of tolvaptan in the treatment of body fluid retention or hyponatremia, the effect of tolvaptan on the prognosis of patients with hepatic ascites has not been fully investigated.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A total of 628 patients with hepatic ascites who were treated with diuretics (furosemide, spironolactone, or tolvaptan) between 2007 and 2017 were enrolled and divided into two groups: those who received tolvaptan (original tolvaptan group, <jats:italic>n</jats:italic> = 278) and those who did not (original control group, <jats:italic>n</jats:italic> = 350). The cumulative survival rates between the groups were compared and the factors associated with survival in patients with hepatic ascites were identified using a Cox regression analysis. In addition, propensity score matching was applied in patients who started conventional diuretics for new‐onset hepatic ascites after September 2013 (pre‐matching tolvaptan group, <jats:italic>n</jats:italic> = 177; pre‐matching control group, <jats:italic>n</jats:italic> = 63), and the cumulative survival rates were compared between the post‐matching tolvaptan and control groups.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The survival rate was significantly higher in the tolvaptan group than the control group (<jats:italic>P</jats:italic> = 0.005), and tolvaptan therapy was identified as an independent factor associated with survival (hazard ratio 0.721 for death relative to control, <jats:italic>P</jats:italic> < 0.001). The propensity score‐matched comparison also showed a significantly higher survival rate in the tolvaptan group (<jats:italic>n</jats:italic> = 51) than in the control group (n = 51) (<jats:italic>P</jats:italic> = 0.009).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>This study suggests that tolvaptan might improve the prognosis of patients with hepatic ascites.</jats:p></jats:sec>

DOI： 10.1111/hepr.13337

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)アークメディア  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Previous studies have suggested an association between the use of direct‐acting antiviral agents (DAAs) for treating hepatitis C virus (HCV) infection and the resulting decrease in the incidence of hepatocellular carcinoma (HCC); however, it is unclear whether DAAs prevent the recurrence of HCC after curative treatment for HCC. This study aimed to prospectively investigate HCC recurrence and its predictors after curative treatment for HCC.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A total of 3012 patients with chronic HCV infection, with or without cirrhosis, who were treated with DAAs were enrolled between January 1, 2015 and January 31, 2017 as per the institutional review board approved study protocol at 15 institutions, including 10 university hospitals and five high‐volume centers in the Kyusyu area of Japan. Of the 3012 patients, 459 patients who had HCC but were cured with surgery or ablation therapy (curative treatment) before the use of DAAs were included in the analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>During a mean follow‐up period of 29.4 months, 217 (47.2%) patients developed HCC recurrence. The median time to recurrence was 34.0 months, and the 1‐, 2‐, and 3‐year cumulative HCC recurrence rates were 27.1%, 43.4%, and 50.8%, respectively. The risk factors for HCC recurrence were the α‐fetoprotein (AFP) level before DAA therapy (<jats:italic>P</jats:italic> = 0.0047) and the number of curative treatments for HCC before DAA therapy (<jats:italic>P</jats:italic> < 0.0001).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>A high AFP level and multiple occurrences of HCC before DAA therapy are associated with a high risk for HCC recurrence after curative treatment. Follow‐up after DAA therapy should include special attention to the abovementioned risk factors.</jats:p></jats:sec>

DOI： 10.1002/cam4.2061

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestion  

Background/Aims: Esophageal mucosal damage often causes scar tissue, leading to refractory stricture. The aim of this study was to clarify the effect of hepatocyte growth factor (HGF) on esophageal mucosal repair and fibrosis leading to stricture in a rat model of esophageal ulcer. Methods: Esophageal ulcers were induced in rats by topical exposure of the lower esophageal serosa to acetic acid, followed by intraperitoneal administration of HGF (200 μg/day) using an osmotic pump for 7 days. The effect of HGF on esophageal mucosal injury was investigated macroscopically and microscopically. The effect of HGF on epithelial cell proliferation and the expression of genes closely associated with the development of fibrosis were also examined. Results: The administration of HGF for 7 days led to a significant reduction in the ulcerative area and enhanced the proliferation of esophageal epithelial cells. HGF treatment significantly decreased the fibrosis, and subsequently attenuated not only the foreshortening but also the narrowing of the esophagus. The expression levels of tissue inhibitor of metalloproteinase (TIMP)-1, -2, and matrix metalloproteinase (MMP)-2, -9 were significantly decreased among rats treated with HGF. Conclusion: HGF facilitates the repair of esophageal mucosal injury and may also ameliorate the esophageal fibrosis, possibly through enhanced re-epithelization.

DOI： 10.1159/000491876

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)アークメディア  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本消化器病学会-九州支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)アークメディア  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology and Hepatology Australia  

Background and Aim: We confirmed the clinical utility of a three-dimensional navigation system during transarterial chemoembolization. Methods: We evaluated 128 tumors in 91 patients enrolled between May 2015 and August 2016. We evaluated the accuracy of the three-dimensional navigation imaging system for all tumors. We compared the patients who were able to undergo route detection using three-dimensional navigation with previously treated patients who underwent transarterial chemoembolization without using three-dimensional navigation (n = 21). For 38 patients who underwent super-selective microcatheter insertion after a feeding artery was identified by three-dimensional navigation, we confirmed the relationship between the tumors and contrasted liver parenchyma and divided the computed tomography hepatic arteriography findings into four grades. Grade 1: an overlap of > 5 mm, grade 2: an overlap between 0 and 5 mm, grade 3: the borders of the tumor within the liver parenchyma but in contact with the edges, and grade 4: a tumor outside the borders of the liver parenchyma. Results: Using the three-dimensional navigation system, we identified a tumor-feeding artery in 125/128 tumors (97.6%). Furthermore, this system allowed us to significantly reduce the volume of contrast media and the radiation exposure dose in patients undergoing an evaluation. We identified 15 grade 1 tumors (39.5%), 3 grade 2 tumors (7.9%), 11 grade 3 tumors (28.9%), and 9 grade 4 tumors (23.7%) according to our definitions. Conclusion: The three-dimensional navigation is useful not only for patients but also for surgeons who have relatively little experience.

DOI： 10.1111/jgh.14012

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/mco.2017.1434

PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：医学図書出版(株)  

肝細胞増殖因子(HGF)は肝再生を強力に促進する増殖因子で、抗アポトーシス、抗繊維化作用などの多彩な作用を併せ持っている。われわれは長年、組換えヒトHGFの医薬品化に取り組み、2005年に劇症肝炎を対象とした第I/II相臨床試験を医師主導治験の枠組みで実施した。本臨床試験では劇症肝炎患者4例に組換えヒトHGFを反復静脈内投与したが、重篤な有害事象はみられなかった。その後、製薬企業の協力を得てJST研究成果最適展開支援プログラムA-STEP本格研究開発ステージ実用化挑戦タイプ「組換えヒト肝細胞増殖因子を用いた急性肝不全の治療」に採択され、新たに製造した組換えヒトHGFを用いて臨床開発を推進している。(著者抄録)

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncology Letters  

Percutaneous radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) is an effective, standard therapy against small hepatocellular carcinoma (HCC). However, there is debate regarding the effectiveness of RFA combined with TACE (RFA/TACE) compared with RFA alone. These two approaches were compared for the treatment of early HCC. The present study examined 83 HCC tumors in 83 patients treated with RFA between April 2007 and August 2014 at three medical institutions. All HCCs were single hypervascular tumors, with a median diameter of 16 mm (range, 6-30 mm). The overall survival (OS) rate of all patients (n=83) was 97.5% at 1 year, 82.8% at 3 years and 48.6% at 5 years, and the local recurrence rate of all patients was 14.3% at 1 year, 32.3% at 3 years and 36.5% at 5 years. The tumor-free survival (TFS) rate of all patients was 95.1% at 1 year, 56.3% at 3 years and 23.4% at 5 years. Compared with RFA alone, RFA/TACE significantly improved OS (P<0.001), intrahepatic distant recurrence (IDR; P=0.038) and TFS (P=0.010). A univariate analysis of prognostic indicators revealed that age <70 years (P=0.008), aspartate transaminase <40 IU/l (P=0.003), alanine aminotransferase <40 IU/l (P=0.006) and platelet count >10x10⁴/µl (P=0.05) were associated with a high survival rate. Multivariate analysis identified RFA/TACE [hazard ratio (HR), 0.108; P=0.001] as an independent prognostic indicator. RFA/TACE was identified as the only independent indicator of IDR (HR: 0.467; P=0.042) and TFS (HR: 0.452; P=0.012). RFA/TACE improved OS rate, IDR and TFS compared with RFA alone. The data suggested that RFA/TACE should be considered for the treatment of single hypervascular HCC.

DOI： 10.3892/ol.2017.6476

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Plos One  

Background and aims Neutrophil infiltration of the liver is a typical feature of alcoholic liver injury. Human neutrophil peptide (HNP)-1 is an antimicrobial peptide secreted by neutrophils. The aim of this study was to determine if HNP-1 affects ethanol-induced liver injury and to examine the mechanism of liver injury induced by HNP-1. Methods Transgenic (TG) mice expressing HNP-1 under the control of a β-actin-based promoter were established. Ethanol was orally administered to HNP-1 TG or wild-type C57BL/6N (WT) mice. SK-Hep1 hepatocellular carcinoma cells were used to investigate the effect of HNP-1 on hepatocytes in vitro. Results After 24 weeks of ethanol intake, hepatic fibrosis and hepatocyte apoptosis were significantly more severe in TG mice than in WT mice. Levels of CD14, TLR4, and IL-6 in liver tissues were higher in TG mice than in WT mice. Apoptosis was accompanied by higher protein levels of caspase-3, caspase-8, and cleaved PARP in liver tissue. In addition, phosphorylated ASK1, ASK1, phosphorylated JNK, JNK1, JNK2, Bax, Bak and Bim were all more abundant in TG mice than in WT mice. In contrast, the level of anti-apoptotic Bcl2 in the liver was significantly lower in TG mice than in WT mice. Analysis of microRNAs in liver tissue showed that miR-34a-5p expression was significantly higher in TG mice than in WT mice. Furthermore, in the presence of ethanol, HNP-1 increased the apoptosis with the decreased level of Bcl2 in a concentration-dependent manner in vitro.

DOI： 10.1371/journal.pone.0174913

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

症例は66歳、男性。全身倦怠感、発熱、腹痛、食思不振で近医を受診し、血小板減少、肝腎機能障害を認め、当院へ緊急入院となった。腹部超音波検査、CT検査で著明な肝脾腫と脾内占拠性病変、脾出血を認めた。急速に肝不全が進行、播種性血管内凝固症候群(disseminated intravascular coagulation:DIC)も合併し、全身状態は増悪した。第3病日には腹腔内出血を来し、第5病日に死亡した。家族の同意を得て、剖検を行った。肝腫大、著明な脾腫大を認め、脾臓は被膜の破綻、出血を伴い脾破裂をきたしていた。肝臓、脾臓には腫瘍細胞がびまん性に増殖しており、免疫染色にて悪性リンパ腫(diffuse large B-cell lymphoma:DLBCL)と診断した。今回、我々は脾破裂を伴い急性肝不全様の急激な経過を呈した悪性リンパ腫の一例を経験したので文献的考察を含めて報告する。(著者抄録)

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)メディカルレビュー社  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)先端医学社  

飲酒はさまざまな疾患と関連しており、糖尿病や高尿酸血症も例外ではない。慢性的な大量飲酒による膵臓障害は糖尿病の原因となりうるが、適度な飲酒は糖尿病発症を抑制するとの報告もある。飲酒による高尿酸血症の機序として、ATPの過剰消費や産生障害によるアデニンヌクレオチドの分解亢進およびプリン体摂取による尿酸の産生過剰がある。また、大量飲酒による血中乳酸濃度の増加は、尿酸排泄の低下を介して血清尿酸値を上昇させる。(著者抄録)

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

<jats:sec><jats:title>Aim</jats:title><jats:p>Tolvaptan, an oral active vasopressin V2 receptor antagonist, is widely used for hepatic edema in Japan, but its clinical benefits have yet to be fully clarified. The present study evaluated the efficacy of tolvaptan in hepatic edema.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The efficacy and treatment regimen of tolvaptan were evaluated in 150 patients with hepatic edema by analyzing the initial (day 14) and long‐term (day 90) responses to the drug and their predictive factors. All patients were divided into good (Child–Pugh classification B, and absent of advanced hepatocellular carcinoma) and poor hepatic condition groups, and the response rates were compared between the two groups.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The initial response rate was 62%, and the long‐term response rate was 47%. The assessment of predictive factors for response to tolvaptan showed that serum creatinine and C‐reactive protein levels were important predictors of initial response, and that hepatic conditions, such as the Child–Pugh score or presence of hepatocellular carcinoma, as well as initial response, were significant predictors of long‐term response. In addition, both the initial and long‐term response rates and the cumulative survival rate were found to be higher in the good hepatic condition group than in the poor hepatic condition group, respectively (71% vs. 57%, <jats:italic>P</jats:italic> = 0.113; 62% vs. 39%, <jats:italic>P</jats:italic> = 0.009; log–rank test, <jats:italic>P</jats:italic> < 0.001).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These results suggest that tolvaptan may provide high response rates when used early in the course of hepatic edema, or when both hepatic and renal functions are still retained, leading to an improved disease prognosis.</jats:p></jats:sec>

DOI： 10.1111/hepr.12778

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(公社)日本超音波医学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：医学図書出版(株)  

B型急性肝炎は一般的に予後良好で抗ウイルス療法を必要としないが、その他のウイルス性肝炎と比較し、重症化、劇症化の比率が高く、重症度の判定が特に重要である。核酸アナログは、B型慢性肝炎や肝硬変に対して、高い抗ウイルス効果と肝予備能、肝予後の改善効果が得られる薬剤で、急性肝炎重症例や劇症肝炎に対しても投与が推奨されている。しかし、効果発現までに時間を要するため、重症度を的確に判断し、その適応を検討する必要がある。(著者抄録)

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)アークメディア  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：南江堂  

DOI： 10.15106/j00974.2015258623

CiNii Research

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)南江堂  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncology Reports  

The molecular mechanisms underlying the progression of nonalcoholic steatohepatitis (NASH) have not been fully elucidated. The aim of this study was to identify factors involved in NASH progression by analysis of pathophysiological features and gene-expression profiles in livers of STAM mice, a model of NASH-associated hepatocarcinogenesis. C57BL/6N (B6N) mice were injected with streptozotocin to generate STAM mice. Four-week-old male STAM and B6N mice were fed a high-fat diet (HFD) (STAM-F, B6N-F) or a conventional diet (STAM-C, B6N-C) until they were 10, 14, or 18 weeks old. Blood glucose and nonalcoholic fatty liver disease (NAFLD) activity scores of STAM-F were higher than those of STAM-C during all observation periods. STAM-F mice had more severe hepatic fibrosis at 14 weeks, and exhibited higher levels of α-fetoprotein-positive hepatic tumor formation with multiplication than STAM-C mice at 18 weeks. At 14 weeks, cDNA microarray analysis revealed that the hepatic expression of eight mRNAs was ≥30-fold higher in STAM-F than B6N-F mice. The expression of another four genes was increased ≥5-fold in STAM-F than B6N-F mice, and ≥5-fold in B6N-F relative to B6N-C mice. Of the 12 genes, the difference in Sptlc3 mRNA expression was most pronounced, and gradually increased over time, as determined by quantitative RT-PCR in STAM-F mice. In addition, Sptlc3 mRNA expression in STAM-F mice was higher than that in db/db mice that received HFD and in B6N mice fed a choline-deficient L-amino acid (CDAA)-defined diet. In conclusion, a high-fat diet aggravated pathophysiological findings in the liver in NASH mouse models, and the hepatic expression of Sptlc3 mRNA was potentially associated with NASH progression.

DOI： 10.3892/or.2015.3745

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Journal of Gastroenterology  

Most cases of hepatocellular carcinoma (HCC) in Japan develop in the background of chronic liver disease caused by hepatitis C virus (HCV). Recently, however, HCV-associated HCC has been shown to be decreasing, while non-B and non-C HCC (NBNC-HCC), which is negative for HCV and hepatitis B virus infection, has increased. The main cause of NBNC-HCC is alcoholic liver disease, but the recent increase of NBNC-HCC is thought to be due to an increase in patients with nonalcoholic fatty liver disease (NAFLD). Approximately 10 % of NAFLD cases involve nonalcoholic steatohepatitis (NASH), and NASH can progress to liver cirrhosis and its associated complications such as HCC. There are no accurate data on the percentage of NASH-related HCC among all-cause HCC in Japan, because no large-scale investigation has been performed. However, the rate is thought to be about 3 % of overall HCC, which is lower than that in the United States. The incidence of HCC in patients with NASH-related cirrhosis is thought to be 2 % per year, which is lower than that in HCV-related cirrhosis. Risks for NASH-related HCC include advanced hepatic fibrosis, older age, and being male. NAFLD that includes NASH is associated with metabolic syndrome, which includes obesity and diabetes, and metabolic syndrome is a risk factor for HCC. Genetic factors and dietary patterns may also be related to NASH-related HCC. Thus, regular HCC surveillance, as performed for patients with viral chronic liver disease, is required for patients with NAFLD, and diagnostic markers are required for simple, rapid and specific detection of NASH-related HCC.

DOI： 10.1007/s12328-014-0548-5

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

症例1は80歳、男性。2007年肝細胞癌に対して開腹下ラジオ波焼灼療法(RFA)を施行して以降、多発再発に対して肝動注化学塞栓療法(TACE)にて繰り返し加療していた。2013年完全房室ブロックに対してペースメーカー植込み術が行われた。2014年4月肝S4の肝細胞癌再発に対して、バイポーラ電極針2本にてRFAを施行した。焼灼中はペースメーカー設定をVVI modeからVOO modeに変更した。症例2は86歳、男性。2003年完全房室ブロックに対してペースメーカー植込み術が行われた。2014年1月肝S6の肝細胞癌に対して、TACEを施行後、バイポーラ電極針2本にてRFAを追加施行した。焼灼中はペースメーカーの設定(VDD mode)を変更しなかった。2症例共、焼灼中に心電図モニタ上に異常波形の出現は認めず、バイポーラ電極針を用いたRFAは、ペースメーカー植込み症例でも安全に施行できると考えられた。(著者抄録)

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medicine United States  

Endoscopic submucosal dissection (ESD) enables wider tumor resection compared with endoscopic mucosal resection and en bloc resection of superficial esophageal neoplasms. However, ESD may cause difficult-to-treat stricture of the esophagus, and therefore, prediction of and measures against postoperative esophageal stricture are critical. The aim of this study was to evaluate the effect of ESD on superficial esophageal neoplasms and identify risk factors associated with esophageal stricture after ESD.This study included 165 lesions in 120 patients with superficial esophageal neoplasms, including cancer and neoplasia, who underwent ESD from 2009 to 2013.The complete resection rate of superficial esophageal neoplasms by ESD was 90.9%. After ESD, 22 subjects (18.3%) had symptomatic esophageal stricture, 12 (10.0%) had aspiration pneumonia of grade 2, and 7 (5.8%) had mediastinal emphysema of grade 2. Comparison of the 22 subjects with stricture with the 98 subjects without stricture showed significant differences in the rate of resection of >75% of the esophageal circumference, rate of whole circumference resection, and the required time for resection. The tumor size and the size of the resected tissue sample also differed between the 2 groups. The groups did not differ in age, sex, alcohol intake, and smoking; location, macroscopic, and histological tumor findings; chest pain; or use of anticoagulants for comorbidities. In multivariate analysis, tumor size and whole circumference resection were independent risk factors for stricture. Furthermore, in 45 subjects with resection of >75% of the esophageal circumference, whole resection of the esophagus was the only independent risk factor for stricture.This study suggests that ESD has a strong therapeutic effect on superficial esophageal neoplasms; however, a greater extent of resection of the esophagus increases the risk of postoperative esophageal stricture. Preventive measures against development of postoperative stricture require further study.

DOI： 10.1097/MD.0000000000000373

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(公社)日本超音波医学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(公社)日本超音波医学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Plos One  

Background and aims: Glycoprotein nonmetastatic melanoma B (Gpnmb), a transmembrane glycoprotein that is expressed in macrophages, negatively regulates inflammation. We have reported that Gpnmb is strongly expressed in the livers of rats fed a choline-deficient, L-amino aciddefined (CDAA) diet. However, the role of macrophage-expressed Gpnmb in liver injury is still unknown. This study aimed to clarify the characteristics of infiltrating macrophages that express Gpnmb, and the involvement of Gpnmb in the repair process in response to liver injury. Methods: C57BL/6J, DBA/2J [DBA] and DBA/2J-Gpnmb+ [DBA-g+] mice were treated with a single intraperitoneal injection of carbon tetrachloride (CCl<inf>4</inf>) at a dose of 1.0 mL/kg body weight. Mice were sacrificed at predetermined time points, followed by measurement of serum alanine aminotransferase (ALT) levels and histological examination. Expression of Gpnmb, pro-/anti-inflammatory cytokines, and profibrotic/antifibrotic factors were examined by quantitative RT-PCR and/or Western blotting. Immunohistochemistry, fluorescent immunostaining and flow cytometry were used to determine the expression of Gpnmb, CD68, CD11b and α-SMA, phagocytic activity, and the presence of apoptotic bodies. We used quantitative RT-PCR and ELISA to examine TGF-β and MMP-13 expression and the concentrations and supernatants of isolated infiltrating hepatic macrophages transfected with siGpnmb. Results: In C57BL/6J mice, serum ALT levels increased at two days after CCl<inf>4</inf> injection and decreased at four days. Gpnmb expression in the liver was stimulated four days after CCl<inf>4</inf> injection. Histological examination and flow cytometry showed that Gpnmb-positive cells were almost positive for CD68-positive macrophages, contained engulfed apoptotic bodies and exhibited enhanced phagocytic activity. Isolated infiltrating hepatic macrophages transfected with siGpnmb showed high MMP-13 secretion. There was no significant difference in the magnitude of CCl<inf>4</inf>-induced liver injury between DBA-g+ and DBA mice. However, hepatic MMP-13 expression, as well as α-SMA expression and collagen production, increased significantly in DBA-g+ compared with DBA mice. Conclusions: Gpnmb-positive macrophages infiltrate the liver during the recovery phase of CCl4-induced acute liver injury and contribute to the balance between fibrosis and fibrolysis in the repair process following acute liver injury.

DOI： 10.1371/journal.pone.0143413

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

Background: Human T-lymphotropic virus type 1 (HTLV-1) may worsen the clinical course of hepatitis C virus (HCV) infection. The aim of this study was to investigate whether HTLV-1 coinfection influences the clinical characteristics of patients with HCV infection.Results: The seroprevalence of anti-HTLV-1 antibodies was significantly higher in patients with HCC (21.1 %) than those without HCC (10.5 %, P = 0.001). This significant difference was observed in female patients (29.5 vs. 8.5 %, P < 0.001), but not in male patients (16.5 vs. 12.9 %, P = 0.501). In multivariate analysis, anti-HTLV-1 antibody positivity was independently associated with HCC in female patients [odds ratio (OR), 5.029; 95 % confidence interval (95 % CI), 1.760–14.369; P = 0.003], in addition to age (≥65 years; OR, 10.297; 95 % CI, 4.322–24.533; P < 0.001), platelet count (<15 × 10⁴/μL; OR, 2.715; 95 % CI, 1.050–7.017; P = 0.039), total bilirubin (≥1 mg/dL; OR, 3.155; 95 % CI, 1.365–7.292; P = 0.007), and total cholesterol (≤160 mg/dL; OR, 2.916; 95 % CI, 1.341–6.342; P = 0.007). In contrast, HTLV-1 coinfection was not associated with HCC in male patients, although age, alcohol consumption, platelet count, and albumin were independently associated with HCC.Methods: This retrospective study included 523 consecutive patients from January 2001 to December 2010 with chronic liver disease due to HCV infection, in whom serum anti-HTLV-1 antibodies were examined. Among these patients, 265 were diagnosed with hepatocellular carcinoma (HCC).Conclusions: HTLV-1 coinfection may contribute to the development of HCC in patients with chronic HCV infection, especially in females.

DOI： 10.1007/s00535-013-0928-5

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)アークメディア  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本インターベンショナルラジオロジー学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(公社)日本超音波医学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMC Gastroenterology  

Background: Apoptosis inhibitor of macrophage (AIM) and adipocytokines are involved in the metabolic syndrome, which has been putatively associated with the progression of chronic hepatitis C (CHC). However, the association between these cytokines and CHC is not fully elucidated. The aim of this study is to test whether serum levels of AIM and adipocytokines are associated with histological features, homeostasis model assessment-insulin resistance index (HOMA-IR), or whole body insulin sensitivity index (WBISI) in CHC patients.Methods: Serum samples were obtained from 77 patients with biopsy-proven CHC. In 39 patients without overt diabetes mellitus, a 75 g oral glucose tolerance test (OGTT) was performed and HOMA-IR and WBISI were calculated.Results: A serum AIM level of ≥1.2 μg/ml was independently associated with advanced hepatic fibrosis (F2 or F3) (odds ratio [OR], 5.612; 95% confidence interval [CI], 1.103-28.563; P = 0.038) based on a multivariate analysis, but there was no significant association between AIM and hepatic steatosis or inflammation. Furthermore, a serum leptin level of ≥8.6 ng/ml was independently associated with the presence of hepatic steatosis (≥5%) (OR, 6.195; 95% CI, 1.409-27.240; P = 0.016), but not hepatic fibrosis or inflammation. No relationship was observed between levels of adiponectin or resistin and hepatic histological parameters based on a multivariate analysis. Although serum levels of leptin, resistin, and adiponectin were significantly correlated with HOMA-IR and WBISI, there was no significant relationship between serum AIM levels and HOMA-IR or WBISI, respectively.Conclusion: High serum levels of AIM in CHC patients are potentially related to advanced hepatic fibrosis. AIM and adipocytokines are possibly associated with pathological changes via a different mechanism. © 2014 Mera et al.; licensee BioMed Central Ltd.

DOI： 10.1186/1471-230X-14-27

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Molecular Medicine  

The effect of hypertension on non-alcoholic fatty liver disease (NAFLD) remains unclear at the molecular level. In this study, we investigated the effects of hypertension on the degree of hepatic steatosis, liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined (CDAA) diet in spontaneously hypertensive rats (SHRs). Seven-week-old male SHRs were fed standard chow with high or normal salt concentrations for 7 weeks, followed by a CDAA diet containing high or normal salt for an additional 8 or 24 weeks. Hepatic steatosis was assessed using hepatic triglyceride levels and Oil red O staining. Hepatic fibrosis was evaluated using Sirius red and Azan staining. Systolic blood pressure (SBP) gradually increased with a high-salt diet and was significantly higher after 7 weeks of feeding with highsalt vs. normal-salt chow. After 8 weeks on the CDAA diet, the degree of hepatic steatosis did not differ between the high-salt and normal-salt groups; however, alanine aminotransferase and fasting blood glucose levels were significantly higher and hepatic mRNA levels for interleukin (IL)-10 and heme oxygenase (HO)-1 were significantly lower in the high-salt group compared with the normal-salt group. After 24 weeks on the CDAA diet, the high-salt group had significantly more severe hepatic fibrosis and a higher hepatic mRNA expression of á-smooth muscle actin and lower hepatic IL-10 and HO-1 mRNA levels compared with the normal-salt group. In conclusion, our results indicate that hypertension is a potential risk factor for liver injury and hepatic fibrosis through glucose intolerance and decreased IL-10-mediated or HO-1-induced anti-inflammatory mechanisms.

DOI： 10.3892/ijmm.2013.1544

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(公社)日本超音波医学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Medical Research  

Background: Nonalcoholic fatty liver disease (NAFLD) is a risk for hepatocellular carcinoma (HCC), but the association between a high-fructose diet and HCC is not fully understood. In this study, we investigated whether a high-fructose diet affects hepatocarcinogenesis induced by administration of diethylnitrosamine (DEN). Methods. Seven-week-old male Sprague-Dawley rats were fed standard chow (controls), a high-fat diet (54% fat), or a high-fructose diet (66% fructose) for 8 weeks. All rats were given DEN at 50 μg/L in drinking water during the same period. Precancerous hepatocytes were detected by immunostaining of the placental form of glutathione-S-transferase (GST-P). The number of GST-P-positive hepatocytes was assessed in liver specimens. Results: Serum levels of total cholesterol were similar among the three groups, but serum triglyceride, fasting blood glucose, and insulin levels were higher in the high-fructose group compared to the high-fat group. In contrast, hepatic steatosis was more severe in the high-fat group compared with the high-fructose and control groups, but the incidence of GST-P-positive specimens was significantly higher in the high-fructose group compared to the other two groups. The average number of GST-P-positive hepatocytes in GST-P positive specimens in the high-fructose group was also higher than those in the other two groups. This high prevalence of GST-P-positive hepatocytes was accompanied by higher levels of 8-hydroxydeoxyguanosine in serum and liver tissue. Conclusions: These results indicate that dietary fructose, rather than dietary fat, increases the incidence of precancerous hepatocytes induced by administration of DEN via insulin resistance and oxidative stress in rat. Thus, excessive fructose intake may be a potential risk factor for hepatocarcinogenesis. © 2013 Kumamoto et al.; licensee BioMed Central Ltd.

DOI： 10.1186/2047-783X-18-54

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Neutrophils infiltrate the livers of patients with nonalcoholic steatohepatitis (<jats:styled-content style="fixed-case">NASH</jats:styled-content>). Human neutrophil peptides (<jats:styled-content style="fixed-case">HNP</jats:styled-content>s) induce cytokine and chemokine production under inflammatory conditions, which may contribute to the progression of <jats:styled-content style="fixed-case">NASH</jats:styled-content>. In this study, we focused on the effects of <jats:styled-content style="fixed-case">HNP</jats:styled-content>‐1 on hepatic steatosis and fibrosis in a mouse model of <jats:styled-content style="fixed-case">NASH</jats:styled-content> induced by a choline‐deficient, L‐amino acid–defined (<jats:styled-content style="fixed-case">CDAA</jats:styled-content>) diet.</jats:p></jats:sec><jats:sec><jats:title>Materials & Methods</jats:title><jats:p>We generated transgenic mice expressing <jats:styled-content style="fixed-case">HNP</jats:styled-content>‐1 under the control of a β‐actin–based promoter. <jats:styled-content style="fixed-case">HNP</jats:styled-content>‐1 transgenic and wild‐type C57<jats:styled-content style="fixed-case">BL</jats:styled-content>/6N mice were fed a <jats:styled-content style="fixed-case">CDAA</jats:styled-content> diet for 16 weeks to induce hepatic steatosis and fibrosis. Serological and histological features were examined, and the effects of <jats:styled-content style="fixed-case">HNP</jats:styled-content>‐1 on hepatic stellate cell lines were assessed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:styled-content style="fixed-case">HNP</jats:styled-content>‐1 transgenic and wild‐type mice fed the <jats:styled-content style="fixed-case">CDAA</jats:styled-content> diet showed no significant differences in serum alanine aminotransferase levels or the degree of hepatic steatosis based on Oil red O staining and hepatic triglyceride content. In contrast, Sirius Red and Azan staining showed significantly more severe hepatic fibrosis in <jats:styled-content style="fixed-case">HNP</jats:styled-content>‐1 transgenic mice compared with wild‐type mice. In addition, significantly more α‐smooth muscle actin–positive hepatic stellate cells were observed in the transgenic mice than in the wild‐type mice. Finally, the proliferation of the <jats:styled-content style="fixed-case">LI</jats:styled-content>90 hepatic stellate cell line increased in response to <jats:styled-content style="fixed-case">HNP</jats:styled-content>‐1.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our data indicate that <jats:styled-content style="fixed-case">HNP</jats:styled-content>‐1 enhances hepatic fibrosis in fatty liver by inducing hepatic stellate cell proliferation. Thus, neutrophil‐derived <jats:styled-content style="fixed-case">HNP</jats:styled-content>‐1 may contribute to the progression of <jats:styled-content style="fixed-case">NASH</jats:styled-content>.</jats:p></jats:sec>

DOI： 10.1111/liv.12203

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PubMed

CiNii Research

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)医薬ジャーナル社  

わが国では肥満人口の増加に伴い、非アルコール性脂肪性肝疾患(NAFLD)/非アルコール性脂肪肝炎(NASH)の増加が懸念されている。脂肪肝から炎症、線維化を伴うNASHへ進行し、肝硬変や肝癌を合併する可能性があることは知られているが、その頻度や進展速度、リスクファクターなどは十分明らかにされていない。また、非B非C型肝癌が近年増加してきているのはNAFLD/NASHが寄与しているからと推測されているが、明確な疫学データがないのが現状である。NASHの診断には肝生検が必要であるが、侵襲的検査であり、簡便に測定でき、特異性の高いバイオマーカーを用いたNASH診断法の確立が必要である。治療は食事、運動療法などの生活習慣の改善が基本であるが、薬物療法については、エビデンスレベルの高い報告が少なく、標準的治療法が確立されていない。現状では、NAFLD/NASHの治療を行う際には、NAFLD/NASHがメタボリック症候群の肝における表現系と考え、全身的な疾患として捉えることが重要であるが、NAFLD/NASHの病態を考慮した新しい治療法の創出が期待される。(著者抄録)

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Medicine Reports  

Certain hepatitis C virus (HCV) carriers exhibit persistently normal alanine aminotransferase (ALT) levels (PNALT) (≤30 IU/l) accompanied by normal platelet counts (≥15x10⁴/μl); these individuals show milder disease activity and slower progression to cirrhosis. This study aimed to elucidate the characteristics of HCV carriers with PNALT using serum proteomics. The first group of subjects, who underwent clinical evaluation in the hospital, consisted of 19 HCV carriers with PNALT (PNALT-1) and 20 chronic hepatitis C (CHC-1) patients. The second group of subjects was part of a cohort study on the natural history of liver disease, and included 37 PNALT (PNALT-2) and 30 CHC (CHC-2) patients. Affinity bead-purified serum protein was subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis. Serum proteomics showed that 6 protein peaks with mass-to-charge ratios ranging from 1,000 to 3,000 differed significantly between the PNALT-1 and CHC-1 groups. Among these peaks, a 1738-m/z peak protein was identified as a fragment of complement component 4 (C4) and correlated significantly with serum C4a concentrations as determined by enzyme immunoassay. Serum C4a levels were also significantly higher in the PNALT-2 group compared to the CHC-2 group and healthy volunteers. Furthermore, in the PNALT-2 group, serum C4a levels negatively correlated with transaminase levels, but not with other biochemical tests, HCV core antigen levels, peripheral blood cell counts or serum hepatic fibrosis markers. This study indicates that host factors such as C4a not only differ between HCV carriers with PNALT and CHC, but that proteomic approaches could also contribute to the elucidation of factors in PNALT as more differences are discovered.

DOI： 10.3892/mmr.2012.924

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1402106030

CiNii Research

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)医学書院  

＜ポイント＞★肝硬変の原因として,アルコール性肝硬変は13.6%,非アルコール性脂肪肝炎(NASH)肝硬変は2.1%と報告されている.★アルコール性肝硬変,NASH肝硬変にも肝癌のリスクがある.★アルコール性肝硬変は長期の大量飲酒が原因となるが,女性,糖尿病や肥満の合併者では,飲酒量が少なくても肝硬変に至る.★NASHは肝に脂肪滴が沈着しているが,肝硬変に至ると,しばしば脂肪滴が減少するため,診断が困難となる.★アルコール性肝障害とNASHの発症には脂肪肝が関与し,病理組織は類似している.(著者抄録)

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(公社)日本小児科学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hepatitis Monthly  

Hepatitis C virus (HCV) infection causes chronic hepatitis, which frequently leads to hepatic fibrosis and hepatocellular carcinoma (HCC). Alanine aminotransferase (ALT) is a biomarker of hepatocyte injury and is associated with the progression of hepatic fibrosis. Advanced hepatic fibrosis also predisposes HCV carriers to a risk of HCC. In contrast, some cases with persistent HCV infection have normal ALT levels that persist for a long time, and these HCV carriers have no or mild hepatitis and hepatic fibrosis. These HCV carriers are defined as persistent normal ALT (PnALT) cases and their risk of HCC is low compared to HCV carriers with abnormal ALT. However, there are various definitions of normal ALT and PnALT, and advanced hepatic fibrosis may be missed without a liver biopsy. In addition, there is also a risk of ALT elevation in HCV carriers with PnALT, which increases the risk of progression to hepatic fibrosis and HCC. Most HCV carriers with PnALT have asymptomatic or nonspecific symptoms. HCV carriers with PnALT are also considered to be responsive to interferon-based treatment. Thus, assessment of hepatic fibrosis is important in HCV carriers, and the eradication of HCV infection is more likely in HCV carriers with evidence of hepatic fibrosis, regardless of their ALT levels. © 2012 Kowsar M. P. Co. All rights reserved.

DOI： 10.5812/hepatmon.829

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：World Journal of Gastroenterology  

AIM: To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: Sixty-four consecutive patients who were admitted to Kagoshima University Medical and Dental Hospital were enrolled in this retrospective study. All patients had chronic liver disease (CLD) due to infection with HCV. Thirty patients with HCV-related HCC, 34 with HCV-related CLD without HCC (non-HCC), and 20 healthy volunteers (HVs) were enrolled. Possible associations between serum manganese superoxide dismutase (MnSOD) and thioredoxin (TRX) levels and clinical parameters or patient prognosis were analyzed over a mean follow-up period of 31.7 mo. RESULTS: The serum MnSOD levels were significantly higher in patients with HCV-related HCC than in patients without HCC (P = 0.03) or HVs (P < 0.001). Similarly, serum TRX levels were also significantly higher in patients with HCV-related HCC than in patients without HCC (P = 0.04) or HVs (P < 0.01). However, serum levels of MnSOD and TRX were not correlated in patients with HCC. Among patients with HCC, the overall survival rate (OSR) was lower in patients with MnSOD levels ≥ 110 ng/mL than in patients with levels < 110 ng/mL (P = 0.01), and the OSR tended to be lower in patients with TRX levels < 80 ng/mL (P = 0.05). In addition, patient prognosis with HCC was poorest with serum MnSOD levels ≥ 110 ng/mL and serum TRX levels < 80 ng/mL. Furthermore, a multivariate analysis using a Cox proportional hazard model and serum levels of five factors (MnSOD, prothrombin time, serum albumin, serum α-fetoprotein (AFP), and serum des-γ-carboxy prothrombin) revealed that MnSOD levels ≥ 110 ng/mL (risk ratio: 4.12, 95% confidential interval: 1.22-13.88, P = 0.02) and AFP levels ≥ 40 ng/mL (risk ratio: 6.75; 95% confidential interval: 1.70-26.85, P < 0.01) were independent risk factors associated with a poor patient prognosis. CONCLUSION: Serum MnSOD and TRX levels are potential clinical biomarkers that predict patient prognosis in HCV-related HCC. © 2011 Baishideng. All rights reserved.

DOI： 10.3748/wjg.v17.i44.4890

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncology Reports  

The fucosylated fraction of α-fetoprotein (AFP-L3) is a specific marker for hepatocellular carcinoma (HCC). However, conventional AFP-L3% (c-AFP-L3%) has not always been reliable in cases with low serum α-fetoprotein (AFP) levels. In this study, we evaluated the clinical utility of a newly developed assay, highly sensitive AFP-L3% (hs-AFP-L3%). Subjects included 74 patients with benign liver disease (BLD), including chronic hepatitis and cirrhosis, and 94 with HCC. Serum hs-AFP-L3% was significantly higher than c-AFP-L3% in patients with early-stage HCC (solitary or <20 mm in diameter). Additionally, hs-AFP-L3% was significantly increased in patients with well-differentiated HCC. In patients with serum AFP <20 ng/ml, the sensitivities of c-AFP-L3% and hs-AFP-L3% were 12.5 and 44.6%, respectively, at a cut-off value of 5%. In 59 BLD patients with serum AFP <20 ng/ml, the HCC-positive rate in patients with hs-AFP-L3% =5% was significantly higher compared to those with hs-AFP-L3% <5% during the follow-up period (median, 35 months; range, 5-48 months). Importantly, none of the BLD patients with both serum AFP <20 ng/ml and hs-AFP-L3% <5% developed HCC. These results indicated that hs-AFP-L3% is useful for early detection of HCC in BLD patients, even for those with serum AFP <20 ng/ml. Furthermore, since hs-AFP-L3% increases before HCC is detectable by various advanced imaging modalities, this assay may help identify BLD patients with a higher risk of HCC.

DOI： 10.3892/or.2011.1425

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

Background Metabolic syndrome, which includes obesity, hyperglycemia, dyslipidemia, and hypertension, is a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD). Cigarette smoking is a well-known risk factor for metabolic syndrome, but the epidemiological impact of cigarette smoking on development of NAFLD is unclear. Methods In this retrospective study, 2,029 subjects underwent a complete medical health checkup in 1998 and again in 2008. Those who were positive for hepatitis B surface antigen or hepatitis C virus antibody, or had an alcohol intake of >20 g/day as assessed by questionnaire, were excluded. Fatty liver was diagnosed by abdominal ultrasonography. Independent risk factors associated with the development of NAFLD were determined by multiple logistic regression analysis. Smoking status was expressed using the Brinkman index (BI), which was calculated as the number of cigarettes smoked per day multiplied by the number of years of smoking. Results Of 1,560 subjects without NAFLD in 1998, 266 (17.1%) were newly diagnosed with NAFLD in 2008. Multiple logistic analysis identified age [adjusted odds ratio (AOR) 0.95, 95% confidence interval (95% CI) 0.94-0.97], male sex (AOR 1.46, 95% CI 1.01-2.10), body mass index C25 (AOR 3.08, 95% CI 2.20-4.32), dyslipidemia (AOR 1.79, 95% CI 1.25-2.58) and cigarette smoking (AOR 1.91, 95% CI 1.34-2.72) as risk factors associated with the development of NAFLD. Smoking status at baseline was also associated with the development of NAFLD (BI 1-399: AOR 1.77, 95% CI 1.02-3.07, BI C400: AOR 2.04, 95% CI 1.37-3.03). Conclusion Cigarette smoking is an independent risk factor for onset of NAFLD.

DOI： 10.1007/s00535-011-0376-z

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nippon Rinsho Japanese Journal of Clinical Medicine  

The liver is the main metabolic organ of the body and is strongly associated with lifestyle-related diseases in which abnormal metabolism of glucose and lipid are the main manifestations. Recently, the prevalence of nonalcoholic fatty liver disease(NAFLD), including nonalcoholic steatohepatitis (NASH), has been increasing due to a higher rates of obesity. It has been reported that the presence of NAFLD/NASH and associated liver dysfunction are predictors for cardiovascular disease. In addition, attention has been paid to the link between chronic hepatitis C and lifestyle-related diseases such as obesity and insulin resistance. Atherosclerosis is an important risk factor for cardiovascular disease and is associated with lifestyle-related diseases. Thus, chronic liver disease seems to be strongly associated with atherosclerosis. Cardiovascular disease induced by atherosclerosis should be attended to along with liver cirrhosis and hepatocellular carcinoma, and medications for lifestyle-related diseases are needed in patients with chronic liver disease.

Scopus

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)日本臨床社  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

25歳女性。20歳時からアルコールを多飲、入院加療歴があった。2009年12月初旬から倦怠感、発熱、黄疸が出現、症状発現15日後に当科入院した。重症型アルコール性肝炎と診断、アンチトロンビン(AT)濃縮製剤などの抗凝固療法を行った。全身状態、肝機能とも改善傾向であったが、血圧測定後に出現した左上腕の皮下血腫が体幹まで拡大し貧血が進行、造影CTでは左上腕部に筋肉内血腫を認めた。圧迫止血を強化し、血腫の進展は止まったが、持続的なAT-III低下に対して再度AT濃縮製剤を投与したところ、筋肉内血腫の増悪と貧血の進行がみられた。急性肝不全では抗凝固療法が有用とされるが、筋肉内血腫で死亡した症例も報告されており注意が必要である。(著者抄録)

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)アークメディア  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(株)日本臨床社  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Medical Association Journal  

When diagnosing patients with liver disorders, it is important to employ appropriate history taking and physical examination to narrow down the differential diagnoses that are suggested by patterns of abnormal liver functions (characterized by liver cell damage, cholestasis, or a combination of both) and to accurately determine the causative diseases on the basis of blood and imaging tests findings. Obtaining family history and past history concerning the chances of infection are important to differentiate viral diseases from non-viral ones. Although patients with mild impairment of liver function are often asymptomatic, it should be borne in mind that abnormal liver function tests are not unusual in patients with non-hepatic diseases such as thyroid disease. A patient with jaundice should first be examined for obstructive jaundice by abdominal ultrasonography or other diagnostic techniques. On the other hand, it is also important to evaluate the severity of liver disease in terms of hepatic reserve. In particular, in cases of acute hepatitis, it is necessary to evaluate hepatic reserve quickly and serially from early on to determine the rate of progress to reach severe or fulminant state. In addition, evaluation of hepatic reserve in liver cirrhosis is important not only for prognostification but also for selecting candidates for liver transplant and choosing the appropriate treatment of hepatocellular carcinoma associated with liver cirrhosis.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本臨床プロテオーム研究会  

DOI： 10.14905/jscp.2010.0_90-2

CiNii Research

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：大道学館出版部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(公社)日本医師会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本皮膚科学会-西部支部  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本肝臓学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：John Wiley & Sons Australia, Ltd  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本循環器学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本皮膚科学会-西部支部  

担当ページ：476-479  

担当ページ：37-39  

担当ページ：22-31  

担当ページ：20-23  

担当ページ：56-58  

記述言語：日本語   出版者・発行元：(株)先端医学社  

わが国における肝細胞癌(HCC)は、男性の癌死因の第4位、女性では第6位で、その死亡者数は年間約3万人であり、肝臓病の死因の大部分を占める。画像診断などの進歩により早期診断が可能となってきたが、高い再発率や、非B非C型HCCの増加、進行HCCに対する効果の高い治療薬がないなど、問題点も多い。プロテオーム解析は試料中に含まれるタンパク質を網羅的に解析できる手法であり、試料の分離法と質量分析法の進歩により、生体サンプル中の微量なタンパク質の同定が可能となった。近年、HCCの早期診断や治療効果予測などに有用なバイオマーカー探索がプロテオーム解析技術を用いておこなわれるようになり、多数のバイオマーカー候補が同定されている。HCCに特異的なバイオマーカーを同定し、簡便に測定できるようになれば、早期診断や治療効果の向上に寄与でき、予後改善につながる可能性がある。(著者抄録)

記述言語：日本語   出版者・発行元：(株)インナービジョン  

開催年月日： 2017年

会議種別：ポスター発表  

開催年月日： 2017年

会議種別：ポスター発表  

開催年月日： 2016年

会議種別：ポスター発表  

開催年月日： 2016年

会議種別：ポスター発表  

開催年月日： 2016年

会議種別：ポスター発表  

開催年月日： 2010年

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