研究者詳細 - 伊藤　隆徳

Long-term outcomes of viral eradication in patients with hepatitis C virus infection and mild hepatic fibrosis.

Kumada T, Toyoda H, Yasuda S, Tada T, Ito T, Tanaka J

Journal of viral hepatitis 28 巻 ( 9 ) 頁： 1293 - 1303 2021年9月

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 Viral Hepatitis

The impact of antiviral therapy on clinical outcomes in patients with hepatitis C virus (HCV) infection and mild liver fibrosis (FIB-4 score <1.45) is not well understood. We aimed to clarify the impact of viral eradication on hepatocarcinogenesis and mortality in patients with mild fibrosis.The subjects were 657 patients who achieved sustained virologic response (SVR) (Clearance group) and 586 patients who did not receive antiviral therapy or did not achieve SVR (No clearance group). We applied inverse probability weighting because the groups had different baseline characteristics. Multivariate proportional hazards models were used to analyse factors associated with hepatocarcinogenesis and mortality using a time-dependent covariate. In addition, we compared the mortality rate of the Clearance group stratified by age to the mortality rate of the general population.Clearance of HCV RNA was significantly associated with hepatocarcinogenesis and all-cause, liver-related and non–liver-related mortality (adjusted hazard ratios [95% confidence interval], 0.2653 [0.1147–0.6136, p = 0.0019], 0.3416 [0.2157–0.5409, p < 0.0001], 0.2474 [0.0802–0.8917, p = 0.0381] and 0.4118 [0.2449–0.6925, p = 0.0008], respectively). The Clearance group had significantly higher mortality than the general population matched by age, sex and follow-up duration (p < 0.0001). However, there were no significant differences between patients who achieved SVR before age 50 and the general population matched by age, sex and follow-up duration (p = 0.1570). HCV eradication in patients with mild fibrosis reduces liver-related and non–liver-related mortality. If HCV is eradicated before age 50, prognosis is likely be similar to that of the age-matched and sex-matched general population. (249 words).

DOI： 10.1111/jvh.13562

Transient deterioration of albumin-bilirubin scores in early post-dose period of molecular targeted therapies in advanced hepatocellular carcinoma with 50% or higher liver occupation: A STROBE-compliant retrospective observational study. Open Access

Muto H, Kuzuya T, Ito T, Ishizu Y, Honda T, Ishikawa T, Ishigami M, Fujishiro M

Medicine 100 巻 ( 31 ) 頁： e26820 2021年8月

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

AbstractReal-world clinical cases of molecularly targeted agent (MTA) administration to patients with advanced hepatocellular carcinoma (HCC) with ≥50% liver occupation have been reported, but treatment outcomes have rarely been described. We have encountered several cases in which albumin-bilirubin (ALBI) scores deteriorated markedly and C-reactive protein (CRP) levels elevated in the early post-dose period. The present study therefore investigated early clinical changes in ALBI score and CRP levels after initiating MTA in advanced HCC patients with ≥50% liver occupation, focusing on antitumor response at 6weeks.This retrospective study included 46 HCC patients with liver occupation ≥50% and 191 patients with <50%, Child-Pugh score ≤7, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1, who were treated with sorafenib or lenvatinib as first-line systemic therapy at our hospital between June 2011 and January 2020. We analyzed their medical records up to March 2020 and investigated the outcomes and changes in CRP and ALBI scores classified according to antitumor response at 6weeks.Overall survival was significantly longer in patients with partial response (PR)+stable disease (SD) (13.7months) than in patients with progressive disease (PD) (1.7months, P<.001) in the ≥50% group. Patients with antitumor response of PR+SD at 6weeks in the ≥50% group showed more marked deterioration of ALBI score at 2weeks than those in the <50% group. These significant differences between groups had again disappeared at 4 and 6weeks. Focusing on patients with PD at 6weeks, ALBI score deteriorated over time in both groups. Regarding CRP, on 6-week PR+SD patients, a significant increase in CRP levels at 1 and 2weeks was evident in the >50% group compared to the <50% group. These significant differences between groups had again disappeared at 4 and 6weeks. In PD patients, no difference between groups in CRP elevation occurred at 1 and 2weeks.In MTA treatment for patients with ≥50% liver occupation, to obtain an antitumor response of PR+SD, adequate management might be important considering transient deteriorated ALBI scores and elevated CRP levels.

DOI： 10.1097/MD.0000000000026820

The impact of hepatitis C virus eradication on hepatocarcinogenesis in haemophiliacs

Inukai, Y; Imai, N; Yamamoto, K; Ito, T; Ishizu, Y; Honda, T; Ishigami, M

JOURNAL OF HEPATOLOGY 75 巻頁： S787 - S788 2021年7月

Quality of Life in patients with nonalcoholic fatty liver disease: Structure and related factors focusing on illness uncertainty

Ozawa N., Sato K., Sugimura A., Maki S., Tanaka T., Yamamoto K., Ito T., Ishizu Y., Kuzuya T., Honda T., Ishigami M., Fujishiro M., Ishikawa T., Ando S.

Japan Journal of Nursing Science 18 巻 ( 3 ) 2021年7月

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

Aim: Patients with nonalcoholic fatty liver disease (NAFLD) have a low quality of life (QOL) and illness uncertainty. This study examined the structure of QOL and associated factors, including illness uncertainty, among individuals with NAFLD. Methods: A cross-sectional survey was conducted using a self-administered questionnaire for outpatients with NAFLD. QOL was measured using the Short Form-8. Dietary habits, physical activity level, illness uncertainty, health locus of control, and knowledge of NAFLD were assessed. Path analysis was used to study the associated factors of QOL and their structure, including uncertainty of disease. Results: Path analysis of 168 NAFLD patients indicated that a high Physical Component Summary score on the Short Form-8—representing physical QOL—was predicted by a body mass index <25 kg/m2 and high educational level. A high Mental Component Summary score—representing mental QOL—was predicted by being male, good dietary habits, low illness uncertainty, and presence of consultants. The model showed satisfactory goodness-of-fit without being rejected by the chi-square test (goodness-of-fit index =.947, adjusted goodness-of-fit index =.917, comparative fit index =.967, root mean square error of approximation = 0.023). Conclusions: Nurses need to work closely with NAFLD patients as consultants, providing adequate information about the causes, treatments, and dietary habits, and focusing on the individual's perception of health. This could reduce illness uncertainty and contribute to the improvement of QOL.

DOI： 10.1111/jjns.12415

Quality of Life in patients with nonalcoholic fatty liver disease: Structure and related factors focusing on illness uncertainty

Ozawa, N; Sato, K; Sugimura, A; Maki, S; Tanaka, T; Yamamoto, K; Ito, T; Ishizu, Y; Kuzuya, T; Honda, T; Ishigami, M; Fujishiro, M; Ishikawa, T; Ando, S

JAPAN JOURNAL OF NURSING SCIENCE 18 巻 ( 3 ) 2021年7月

Quality of Life in patients with nonalcoholic fatty liver disease: Structure and related factors focusing on illness uncertainty

Ozawa Naoki, Sato Kazuki, Sugimura Ayumi, Maki Shigeyoshi, Tanaka Taku, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Ishigami Masatoshi, Fujishiro Mitsuhiro, Ishikawa Tetsuya, Ando Shoko

JAPAN JOURNAL OF NURSING SCIENCE 18 巻 ( 3 ) 2021年7月

Tolerability of Molecular-targeted Agents for Hepatocellular Carcinoma Treatment in Haemophiliacs. Open Access

Yamamoto T, Imai N, Yamamoto K, Ito T, Ishizu Y, Honda T, Okamoto S, Kanematsu T, Suzuki N, Matsushita T, Ishigami M, Fujishiro M

Anticancer research 41 巻 ( 5 ) 頁： 2569 - 2573 2021年5月

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

Background: Hepatocellular carcinoma (HCC) is considered a leading cause of death in patients with haemophilia. Recent advances in the treatment of unresectable HCC with molecular-Targeted agents (MTAs) have led to better clinical outcomes. However, the tolerability of MTAs by haemophilic patients with HCC remains unclear. Aim: This study aimed to compare the tolerability of MTAs in such patients. Patients and Methods: From January 2011 to October 2020, five haemophilic patients with HCC were treated with MTAs. Adverse events were assessed in comparison with 265 non-haemophilic patients with HCC. Results: The prevalence of hand foot skin reaction was not higher in the haemophiliacs than in the non-haemophiliacs, whereas the rate of haemorrhagic events was higher in the haemophiliacs (6.0% versus 40.0%, p=0.037). Conclusion: Haemophiliacs tolerate long-Term MTA use, without the occurrence of life-Threatening complications. However, careful observation and prevention are needed for MTA-related gastrointestinal bleeding in haemophiliacs.

DOI： 10.21873/anticanres.15035

Prediction of Hepatocellular Carcinoma by Liver Stiffness Measurements Using Magnetic Resonance Elastography After Eradicating Hepatitis C Virus. Open Access

Kumada T, Toyoda H, Yasuda S, Sone Y, Ogawa S, Takeshima K, Tada T, Ito T, Sumida Y, Tanaka J

Clinical and translational gastroenterology 12 巻 ( 4 ) 頁： e00337 2021年4月

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 and Translational Gastroenterology

INTRODUCTION:Liver fibrosis stage is one of the most important factors in stratifying the risk of developing hepatocellular carcinoma (HCC). We evaluated the usefulness of liver stiffness measured by magnetic resonance elastography (MRE) to stratify the risk of developing HCC in patients who underwent MRE before receiving direct-acting antivirals (DAAs) and subsequently achieved sustained virological response (SVR).METHODS:A total of 537 consecutive patients with persistent hepatitis C virus who underwent initial MRE before DAA therapy and achieved SVR were enrolled. Factors associated with HCC development were analyzed by univariate and multivariate Cox proportional hazards models.RESULTS:Albumin-bilirubin score ≥ -2.60 (adjusted hazard ratio [aHR] 6.303), fibrosis-4 (FIB-4) score >3.25 (aHR 7.676), and MRE value ≥4.5 kPa (aHR 13.190) were associated with HCC development according to a univariate Cox proportional hazards model. A multivariate Cox proportional hazards model showed that an MRE value ≥4.5 kPa (aHR 7.301) was the only factor independently associated with HCC development. Even in patients with an FIB-4 score >3.25, the cumulative incidence rate of HCC development in those with an MRE value <4.5 kPa was significantly lower than that in patients with an MRE value ≥4.5 kPa.DISCUSSION:Liver stiffness measured by MRE before DAA therapy was an excellent marker for predicting subsequent HCC development in patients with hepatitis C virus infection who achieved SVR. The same results were observed in patients with high FIB-4 scores.

DOI： 10.14309/ctg.0000000000000337

Filtrated Adipose Tissue-Derived Mesenchymal Stem Cell Lysate Ameliorates Experimental Acute Colitis in Mice.

Nishikawa T, Maeda K, Nakamura M, Yamamura T, Sawada T, Mizutani Y, Ito T, Ishikawa T, Furukawa K, Ohno E, Miyahara R, Kawashima H, Honda T, Ishigami M, Yamamoto T, Matsumoto S, Hotta Y, Fujishiro M

Digestive diseases and sciences 66 巻 ( 4 ) 頁： 1034 - 1044 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Digestive Diseases and Sciences

Background: Inflammatory bowel disease (IBD) is a chronic, persistent, and intractable enteritis; however, an effective treatment strategy is yet to be established. Mesenchymal stem cells (MSCs) and their paracrine factors exhibit anti-inflammatory actions and have been proposed as a new therapeutic candidate for IBD treatment, although the efficacy of MSC lysate on enteritis is unclear. Aims: Here, we examined the efficacy and appropriate regimen of filtrated murine adipose-derived mesenchymal stem cell lysate (FADSTL) in an acute colitis mouse model as a novel cell-free MSC therapy. Methods: To confirm the clinical effects of FADSTL, survival rate, body weight, and disease activity index (DAI) were investigated in the DSS-induced colitis mouse model. Further, differences in efficacy with dosing frequency were assessed to optimize the proper regimen. Colon length, histological findings, gene expression of inflammatory mediators and tight junction proteins in colon tissues, and anti-apoptotic effects were also compared in 3-day continuous FADSTL administration and PBS groups. Results: Three-day continuous FADSTL administration significantly improved weight loss and DAI score compared to those in the PBS-treated group, whereas the effect was not observed with single administration. Additionally, colon shortening and histological inflammation were suppressed in the FADSTL-treated group. Further, this treatment decreased gene expression of inflammatory mediators, maintained expression of tight junction proteins in the colon, and showed anti-apoptotic effects. Conclusions: FADSTL effects were dependent on its administration frequency, suggesting the requirement of continuous FADSTL administration. FADSTL improved colitis by maintaining the intestinal barrier function through its anti-inflammatory and anti-apoptotic actions.

DOI： 10.1007/s10620-020-06359-3

Impact of visceral fat accumulation on the prognosis of patients with cirrhosis.

Ishizu Y, Ishigami M, Honda T, Imai N, Ito T, Yamamoto K, Fujishiro M

Clinical nutrition ESPEN 42 巻頁： 354 - 360 2021年4月

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 Nutrition Espen

Background & aims: The impact of obesity, evaluated using body mass index (BMI), on mortality in patients with cirrhosis is controversial. The prognostic impact of visceral fat accumulation, which is recommended as an indicator of obesity-related mortality, is still unknown. This study aimed to clarify the impact of visceral fat accumulation on mortality in patients with cirrhosis. Methods: A total of 335 cirrhotic patients without hepatocellular carcinoma were retrospectively evaluated. The impact of obesity, defined as a visceral fat area ≥100 cm2 at the umbilical level or BMI ≥25 kg/m2 on mortality, was evaluated using competing risk analysis. Results: Of 355 patients, visceral fat accumulation was seen in 147 patients. During the observation period (1340 ± 980 days), 84 patients died, and 17 received liver transplantation. Visceral fat accumulation was not found to be associated with mortality (hazard ratio [HR] 1.423, P = 0.180) in any of the patients. After stratification of the patients, visceral fat accumulation was observed to be associated with a poor prognosis in patients with skeletal muscle depletion (HR 3.804, P = 0.003), but not in those without (HR 1.147, P = 0.660). On the other hand, obesity defined by BMI ≥25 kg/m2 was not found to be associated with mortality in patients with (HR 0.341, P = 0.390) or without skeletal muscle depletion (HR 1.227, P = 0.500). Conclusions: Visceral fat accumulation is a useful index for evaluating obesity and aggravates mortality in cirrhotic patients with skeletal muscle depletion, but not in those without.

DOI： 10.1016/j.clnesp.2021.01.008

The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040. 国際共著

Ito T, Ishigami M, Zou B, Tanaka T, Takahashi H, Kurosaki M, Maeda M, Thin KN, Tanaka K, Takahashi Y, Itoh Y, Oniki K, Seko Y, Saruwatari J, Kawanaka M, Atsukawa M, Hyogo H, Ono M, Ogawa E, Barnett SD, Stave CD, Cheung RC, Fujishiro M, Eguchi Y, Toyoda H, Nguyen MH

Hepatology international 15 巻 ( 2 ) 頁： 366 - 379 2021年4月

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: NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD. Methods: We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD—8 studies) patients. Results: The overall NAFLD prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001), and increased over time (p = 0.015), but not by per-person income or gross prefectural productivity, which increased by 0.64% per year (1983–2012) and is forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC, and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively. Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the NAFLD population, with lean NAFLD persons being older and with a higher all-cause mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02). Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality, but not lean NAFLD. Conclusion: NAFLD prevalence has increased in Japan and may affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the NAFLD population, were older, and had higher mortality.

DOI： 10.1007/s12072-021-10143-4