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  • 1
    Online Resource
    Online Resource
    Validation of albumin, bilirubin, and platelet criteria for avoiding screening endoscopy in patients with advanced fibrosis
    Wiley ; 2020
    In:  Hepatology Research Vol. 50, No. 8 ( 2020-08), p. 996-999
    Details
    In: Hepatology Research, Wiley, Vol. 50, No. 8 ( 2020-08), p. 996-999
    Abstract: The albumin, bilirubin, and platelet (ABP) criteria was proposed to avoid screening endoscopy for detecting high‐risk varices (HRV) and it has high diagnostic accuracy. We carried out a retrospective cross‐sectional study to verify the diagnostic accuracy. Methods A total of 610 patients with advanced fibrosis were enrolled in the study. ABP criteria are defined as follows: albumin 〉 4.0 g/dL, bilirubin 〈 22 μmol/L, and platelets 〉 114 000/μL. Results Background liver disease were hepatitis C/hepatitis B/non‐alcoholic fatty liver disease/others:405 (66.4%)/67 (10.5%)/78 (12.8%)/60 (10.3%). A total of 105 patients (17.2%) had HRV. In multivariate analysis, serum bilirubin 〈 22 μmol/L (HR 2.00, 95% CI 1.2–3.4), albumin 〉 4.0 g/dL (HR 2.56, 95% CI 1.7–3.8), and platelets 〉 114 000/μL (HR 3.52, 95% CI 2.1–5.8) levels were independently associated with no presence of HRV. When the ABP criteria were examined, 200 patients (32.8%) fulfilled the criteria, and 194 patients had no HRV (positive predictive value 97.0%) When classified by etiologies (hepatitis C/hepatitis B/non‐alcoholic fatty liver disease), positive predictive value were 97.7/100/92.0%, respectively. Conclusions The ABP criteria are easy to examine, because they use only standard laboratory tests, and they are available for screening patients who might avoid endoscopy regardless of etiologies.
    Type of Medium: Online Resource
    ISSN: 1386-6346 , 1872-034X
    URL: Issue
    URL: Article
    DOI: 10.1111/hepr.v50.8
    DOI: 10.1111/hepr.13533
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2006439-1
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  • 2
    Online Resource
    Online Resource
    Longitudinal association of magnetic resonance elastography‐associated liver stiffness with complications and mortality
    Wiley ; 2022
    In:  Alimentary Pharmacology & Therapeutics Vol. 55, No. 3 ( 2022-02), p. 292-301
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 55, No. 3 ( 2022-02), p. 292-301
    Abstract: Magnetic resonance elastography (MRE) has the highest diagnostic accuracy for liver fibrosis; however, the association between MRE‐associated liver stiffness and the development of hepatic and extrahepatic complications as well as mortality remains unclear. Aim In this study, we investigated the longitudinal association between MRE‐associated liver stiffness and complications and mortality. Methods This retrospective study included 2373 consecutive patients with chronic liver disease. All patients received standard of care and the development of complications was assessed every 1‐6 months. Results Newly diagnosed hepatocellular carcinoma (HCC), decompensation, major adverse cardiovascular events (MACE), extrahepatic cancer and death were observed in 99, 117, 73, 77 and 170 patients respectively. In multivariable analysis, the adjusted hazard ratios (aHR) (95% confidence interval [CI]) for HCC, decompensation, MACE, extrahepatic cancer and mortality were 1.28 (1.2‐1.4), 1.34 (1.3‐1.4), 0.96 (0.9‐1.1), 1.00 (0.9‐1.1) and 1.17 (1.1‐1.2), respectively, with each 1‐kPa increase in liver stiffness. Similarly, the aHR (95% CI) for HCC, decompensation, MACE, extrahepatic cancer and mortality were 4.20 (2.2‐8.2), 67.5 (9.2‐492), 0.83 (0.4‐1.7), 0.90 (0.5‐1.7) and 2.90 (1.6‐5.4), respectively, in patients with cirrhosis ( 〉 4.7 kPa) compared to those with minimal fibrosis ( 〈 3 kPa). Conclusions Increased MRE‐associated liver stiffness was associated with increased risk for HCC, decompensation and mortality in a dose‐dependent fashion but not with MACE or extrahepatic cancer, implicating a significant role for MRE in liver‐related events and mortality; however, further studies are warranted to explore its role in MACE and extrahepatic cancer.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.v55.3
    DOI: 10.1111/apt.16745
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2003094-0
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    Clinical utility of comprehensive genomic profiling in patients with unresectable primary liver cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. 542-542
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 542-542
    Abstract: 542 Background: Comprehensive genomic profiling (CGP) using tissue and blood specimens is covered by national health insurance for patients who have already received standard systemic therapy in Japan. We investigated the clinical utility of CGP in patients with unresectable primary liver cancer in real-world practice. Methods: We retrospectively investigated the clinical outcome of the patients with unresectable primary liver cancer. All patients received CGP between February 2021 and May 2022 at our institution. Results: 17 patients with unresectable primary liver cancer were included. 10 patients had hepatocellular carcinoma (HCC) and seven had intrahepatic cholangiocarcinoma (ICC). In HCC patients, the treatment line at CGP was 4th (n=5), 5th (n=4), and 6th-line (n=1). The samples were from liver tumor biopsy (n=2), surgical specimens of bone metastases (n=2), and blood (n=6). Clinically meaningful oncogene mutations were detected in all HCC cases. Seven of 10 patients were candidates for clinical trials, and 1 patient showed TMB-high. Six of the 7 patients could not participate in clinical trials due to renal dysfunction, low platelet counts, the immune-related adverse event of past therapy, or HBV infection. One patient with TMB high started pembrolizumab. In ICC patients, the treatment line at CGP was 1st (n=6), and 2nd -line (n=1). The samples were from liver tumor biopsy (n=5), blood (n=1) and surgical specimens of lung metastases (n=1). Clinically meaningful oncogene mutations were detected in all ICC cases. Six of 7 patients were candidates for clinical trials, and 1 patient showed MSI-high. One patient with MSI high started pembrolizumab, and one patient with FGFR2 fusion could use pemigatinib as 3rd line. The Overall survival duration of this patient with ICC (StageⅣB) was 26 months. In total, 13 of 17 patients were candidates for clinical trials, and 4 of 17 patients could receive personalized therapy according to the results of CGP. Conclusions: CGP in patients with unresectable primary liver cancer was useful in real-world practice. However, most patients could not participate in clinical trials because of adverse events associated with previous therapies. The best timing of CGP should be discussed in the future to provide more personalized therapies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.542
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    The impact of relative dose intensity on overall and progression-free survival during cabozantinib therapy for unresectable hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. 569-569
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 569-569
    Abstract: 569 Background: Cabozantinib (CAB) has been approved as 2 nd or later-line worldwide in patients with unresectable hepatocellular carcinoma (u-HCC). There is no data about the relationship between the relative dose intensity (RDI) of CAB and clinical outcome. We investigated the impact of RDI on overall survival (OS) and progression-free survival (PFS) during CAB in real-world practice. Methods: A total of 38 u-HCC patients who received CAB between Jan 2021 and Sep 2022 at our institution were enrolled. Tumor assessments in accordance with RECIST ver1.1 were done using dynamic CT or MRI within 4-8 weeks and every 8-10 weeks thereafter. The RDI of CAB for the first month (1M-RDI) was calculated. Results: The median age was 74 years, and 30 patients were Child-Pugh A. BCLC stage A/B/C were 0/ 11/ 27 patients, and 34 patients were previously received atezolizumab plus bevacizumab. As 2 nd or 3 rd -line, 20 patients received CAB. The median follow-up duration was 7.2 months, and the median PFS was 4.4 months in all patients. The median overall survival (OS) was 16.2 months from the administration of CAB. The objective response rate (ORR) and disease control rate (DCR) was 13.8% and 89.7%. Adverse events (AEs) were observed in all patients, requiring dose reduction in 26 patients (68%) and interruption of CAB in 21 patients (55%). The median 1M-RDI was 35%, and there was no significant difference in PFS between 1M-RDI ≧40% (high 1M-RDI, n=13) and 〈 40% (n=16) (4.1 months vs. 4.7 months, p=0.89). There were no significant differences in age, pretreatment ALBI score, AFP, and major vascular invasion (MVI) between the patients with and without a high RDI. The induction rate of molecular targeted therapies after CAB was 60%. The only significant factor associated with PFS was MVI (HR 0.10, 95%CI 0.02-0.65, p=0.02). In a multivariate analysis, pretreatment ALBI score (HR 5.8, 95% CI 1.2-27.8, P=0.03) and hypertension as AE during CAB (HR 0.29, 95% CI 0.09-0.87, P=0.03) were the significant factors associated with OS. Conclusions: Maintaining a high 1M-RDI of CAB was not associated with OS and PFS in real-world practice. Dose modification is essential for CAB therapy in u-HCC patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.569
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Farside Gravity Field of the Moon from Four-Way Doppler Measurements of SELENE (Kaguya)
    American Association for the Advancement of Science (AAAS) ; 2009
    In:  Science Vol. 323, No. 5916 ( 2009-02-13), p. 900-905
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 323, No. 5916 ( 2009-02-13), p. 900-905
    Abstract: The farside gravity field of the Moon is improved from the tracking data of the Selenological and Engineering Explorer (SELENE) via a relay subsatellite. The new gravity field model reveals that the farside has negative anomaly rings unlike positive anomalies on the nearside. Several basins have large central gravity highs, likely due to super-isostatic, dynamic uplift of the mantle. Other basins with highs are associated with mare fill, implying basalt eruption facilitated by developed faults. Basin topography and mantle uplift on the farside are supported by a rigid lithosphere, whereas basins on the nearside deformed substantially with eruption. Variable styles of compensation on the near- and farsides suggest that reheating and weakening of the lithosphere on the nearside was more extensive than previously considered.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1168029
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2009
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 6
    Online Resource
    Online Resource
    Effect of co-administered inducer or inhibitor on omeprazole pharmacokinetics based on CYP2C19 genotype
    Elsevier BV ; 2019
    In:  Journal of Pharmacological Sciences Vol. 139, No. 4 ( 2019-04), p. 361-366
    Details
    In: Journal of Pharmacological Sciences, Elsevier BV, Vol. 139, No. 4 ( 2019-04), p. 361-366
    Type of Medium: Online Resource
    ISSN: 1347-8613
    URL: Article
    DOI: 10.1016/j.jphs.2019.03.001
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 2136872-7
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  • 7
    Online Resource
    Online Resource
    Clinical Utility of Comprehensive Genomic Profiling in Patients with Unresectable Hepatocellular Carcinoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 3 ( 2023-01-24), p. 719-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-24), p. 719-
    Abstract: This study aimed to investigate the clinical usefulness of comprehensive genomic profiling (CGP) in patients with unresectable hepatocellular carcinoma who received multiple systemic therapies in real-world practice. In this study, all nine patients had gene alterations, and seven were candidates eligible for clinical trials based on the results of CGP. The median number of alterations per patient was four, and the blood sample was used in five patients with extrahepatic metastasis. We revealed the genomic information of the patients who received multiple systemic therapies and reported the utility of blood samples in patients with extrahepatic metastasis. Furthermore, the genomic status in patients treated with multiple molecular-targeted agents, including checkpoint inhibitors, would contribute to developing newer systemic agents. The molecular mechanism of hepatocellular carcinoma (HCC) is partially demonstrated. Moreover, in the patients receiving multiple molecular-targeted therapies, the gene alternations are still unknown. Six molecular-targeted therapies of unresectable HCC (uHCC) and comprehensive genomic profiling (CGP) have been approved in clinical practice. Hence, the utility of CGP in patients with uHCC treated with multiple molecular-targeted agents is investigated. The data of the patients with uHCC who received CGP tests were collected, retrospectively, between February 2021 and May 2022. Gene alterations detected by foundation testing, excluding variants of unknown significance, were reported in all nine patients. The samples for CGP were derived from liver tumor biopsy (n = 2), surgical specimens of bone metastases (n = 2), and blood (n = 5). The median number of systemic therapies was four. Seven patients were candidates eligible for clinical trials. One patient with a high tumor mutation burden (TMB) could receive pembrolizumab after CGP. This study presented genomic alternations after receiving multiple molecular-targeted therapies. However, further investigation needs to be conducted to develop personalized therapies and invent newer agents for treating HCC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15030719
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 8
    Online Resource
    Online Resource
    Impaired brain function improved by l-carnitine in patients with cirrhosis: evaluation using near-infrared spectroscopy
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-08-11)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-08-11)
    Abstract: To evaluate the effects of l -carnitine on impaired brain function in patients with liver cirrhosis. We conducted a retrospective cohort study that included sequential 80 liver cirrhosis patients with impaired brain function evaluated using near-infrared spectroscopy (NIRS). Among them, l -carnitine was administered to 48 patients. The NIRS data and blood ammonia level at baseline and after 8 weeks of treatment were compared between patients administered with l -carnitine ( l -carnitine group) and those who were not (control group). The NIRS data at baseline were similar between the l -carnitine and control groups (0.04 ± 0.04 vs. 0.04 ± 0.05 mMmm, p = n.s), whereas those in the l -carnitine group (n = 48) were significantly better than that of the control group at 8 weeks of treatment (n = 32) (0.103 ± 0.081 vs. 0.040 ± 0.048 mMmm, p  〈  0.001). In the l -carnitine group, 35.4% (17/48) of patients had hyperammonemia. The NIRS data of the l -carnitine group at 8 weeks of treatment were significantly improved than that of the control group, irrespective of baseline ammonia levels (0.11 ± 0.09 vs. 0.04 ± 0.05 mMmm, p = 0.005, and 0.10 ± 0.06 vs. 0.02 ± 0.03 mMmm, p = 0.003, for normal baseline ammonia and elevated ammonia levels, respectively). In the multivariate analysis, l -carnitine administration (odds ratio [OR] 3.51, 95% confidence interval [CI] 1.23–9.99, p = 0.019) and baseline NIRS data of ≤ 0.07 mMmm (OR 5.21, 95% CI 1.69–16.0, p = 0.0041) were found as independent significant factors. l -carnitine improves impaired brain function in patients with liver cirrhosis.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-020-70585-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 9
    Online Resource
    Online Resource
    Conversion surgery for hepatocellular carcinoma after tyrosine kinase inhibitor treatment
    Wiley ; 2022
    In:  JGH Open Vol. 6, No. 5 ( 2022-05), p. 301-308
    Details
    In: JGH Open, Wiley, Vol. 6, No. 5 ( 2022-05), p. 301-308
    Abstract: Conversion surgery (CS), which aims to cure after systematic therapy, is only scarcely reported in the field of hepatocellular carcinoma (HCC). However, advancements in systemic therapy for HCC are expected to increase the candidates eligible for CS because of the higher response rate. The aim of this study was to clarify the characteristics of patients who underwent CS after tyrosine kinase inhibitor (TKI) therapy. Methods In all, 364 patients who were treated with first‐line sorafenib (SOR; n  = 292) and lenvatinib (LEN; n  = 72) from July 2009 to October 2020 were retrospectively enrolled. The endpoint of this analysis was overall survival (OS), and factors associated with CS are revealed. Results Six patients underwent CS after TKI therapy, and of these four (1.4%) and two (2.7%) patients received SOR and LEN, respectively. At baseline, patients who underwent CS were significantly younger (median 52 [range, 46–83] years of age, P  = 0.019), and their etiology included viral hepatitis, especially hepatitis B virus (HBV) ( P  = 0.049). Improvements or maintenance of preoperative modified albumin–bilirubin grade from baseline were observed in five (83.3%) patients, and partial radiologic response was observed in four (66.7%) patients. The median OS and 3‐year survival rate of patients treated with CS were “not reached” and 80.0%, respectively. Conclusion The patients who underwent CS after TKI therapy for HCC experienced long survival, were relatively young, and exhibited radiologic response to TKIs, and their liver function was either maintained or improved. Therefore, CS may lead to a better prognosis in patients with advanced HCC.
    Type of Medium: Online Resource
    ISSN: 2397-9070 , 2397-9070
    URL: Issue
    URL: Article
    DOI: 10.1002/jgh3.v6.5
    DOI: 10.1002/jgh3.12735
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2919809-4
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  • 10
    Online Resource
    Online Resource
    Switching from entecavir to tenofovir alafenamide for maintaining complete virological response in chronic hepatitis B
    Wiley ; 2023
    In:  JGH Open Vol. 7, No. 8 ( 2023-08), p. 567-571
    Details
    In: JGH Open, Wiley, Vol. 7, No. 8 ( 2023-08), p. 567-571
    Abstract: Hepatocellular carcinoma development can be decreased by achieving and maintaining complete virological response (CVR) in chronic hepatitis B. However, it is unclear whether switching from entecavir (ETV) to tenofovir alafenamide (TAF) could achieve and maintain CVR in patients with low‐level viremia (LLV; HBV DNA ≤ 3.3 log IU/mL) or occasional detectable HBV DNA during ETV treatment. Therefore, we aimed to examine whether the switching from ETV to TAF is effective in achieving CVR in patients with LLV or occasional detectable HBV DNA. Methods This study comprised 45 patients who switched from ETV to TAF. All patients received ETV and TAF for 〉 2 years, and the HBV DNA levels were measured every 3 months. Maintaining undetectable HBV DNA during 2‐year period is defined as CVR. The primary endpoint is the CVR rate during ETV and TAF treatment. Results The CVR rate for each of the 2 years of ETV and TAF therapy was 33.3% (15/45) and 68.9% (31/45, P   〈  0.01), respectively, and the CVR rate increased by switching from ETV to TAF. In patients with occasional detectable HBV DNA during ETV treatment (22 patients), 15 achieved CVR and 7 maintained occasional detectable HBV DNA. In patients with LLV during ETV treatment (eight patients), three achieved CVR and five had occasional detectable HBV DNA. Conclusion Switching from ETV to TAF increases the CVR rate in patients with LLV or occasional detectable HBV DNA and could be an alternative treatment option.
    Type of Medium: Online Resource
    ISSN: 2397-9070 , 2397-9070
    URL: Issue
    URL: Article
    DOI: 10.1002/jgh3.v7.8
    DOI: 10.1002/jgh3.12950
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2919809-4
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