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      Impact of M2BPGi on the Hepatocarcinogenesis after the Combination Therapy with Daclatasvir and Asunaprevir for Hepatitis C

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          Abstract

          The clinical significance of mac-2 binding protein glycosylation isomer (M2BPGi) levels based on virological responses due to antiviral therapy has not been fully evaluated. We compared the change before and 24 weeks after the therapy with daclatasvir and asunaprevir (DCV+ASV) of M2BPGi levels with those of other fibrosis markers in 73 chronic hepatitis C cases. Moreover, we examined the association between M2BPGi levels and hepatocarcinogenesis in sustained virological response (SVR) and non-SVR cases. M2BPGi levels were significantly improved at post-treatment week 24 (PTW24) in SVR but not non-SVR cases, whereas the changes of other fibrosis markers showed the same tendency in both SVR and non-SVR cases. M2BPGi levels were well correlated with other fibrosis markers at baseline but not PTW24. The incidence of hepatocellular carcinoma (HCC) was significantly associated with M2BPGi levels at PTW24. The achievement of SVR significantly affected the improvement of M2BPGi levels that best reflected the effect of direct-acting antivirals among the fibrosis markers. Furthermore, M2BPGi levels at PTW24 were also associated with the incidence of HCC in only SVR cases. However, the rapid decrease of M2BPGi levels might reflect the amelioration of liver inflammation rather than the improvement of liver fibrosis, which should be further elucidated.

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          Most cited references31

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          Investigation of the freely available easy-to-use software ‘EZR' for medical statistics

          Y Kanda (2012)
          Although there are many commercially available statistical software packages, only a few implement a competing risk analysis or a proportional hazards regression model with time-dependent covariates, which are necessary in studies on hematopoietic SCT. In addition, most packages are not clinician friendly, as they require that commands be written based on statistical languages. This report describes the statistical software ‘EZR' (Easy R), which is based on R and R commander. EZR enables the application of statistical functions that are frequently used in clinical studies, such as survival analyses, including competing risk analyses and the use of time-dependent covariates, receiver operating characteristics analyses, meta-analyses, sample size calculation and so on, by point-and-click access. EZR is freely available on our website (http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmed.html) and runs on both Windows (Microsoft Corporation, USA) and Mac OS X (Apple, USA). This report provides instructions for the installation and operation of EZR.
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            A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.

            Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment-naive CHC patients who underwent liver biopsy over a 25-month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score > or = 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut-off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients.
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              FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest.

              To optimize the management of patients with chronic hepatitis C virus (HCV) infection, noninvasive tests to determine the degree of hepatic fibrosis have been developed. The aims of this study were (1) to validate a simple, inexpensive, noninvasive test called FIB-4, which combines standard biochemical values (platelets, ALT, AST) and age, in a series of 847 liver biopsies performed in HCV-monoinfected patients; and (2) to compare the results of 780 FIB-4 and FibroTests performed the same day in a series of 592 HCV-infected patients. The FIB-4 index enabled the correct identification of patients with severe fibrosis (F3-F4) and cirrhosis with an area under the receiver operating characteristic curve of 0.85 (95% CI 0.82-0.89) and 0.91 (95% CI 0.86-0.93), respectively. An FIB-4 index 3.25 (kappa = 0.561, P 3.25 (64.6% of the cases) was concordant with FibroTest results in 92.1% and 76%, respectively. For values outside 1.45-3.25, the FIB-4 index is a simple, accurate, and inexpensive method for assessing liver fibrosis and proved to be concordant with FibroTest results.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Biomedicines
                Biomedicines
                biomedicines
                Biomedicines
                MDPI
                2227-9059
                08 June 2021
                June 2021
                : 9
                : 6
                : 660
                Affiliations
                [1 ]Department of Gastroenterology and Hepatology, Kusunoki Hospital, Fujioka, Gunma 375-0024, Japan; satoshi.takakusagi@ 123456gmail.com (S.T.); mrbs1970kyoko@ 123456gmail.com (K.M.); kazukodr8715@ 123456yahoo.co.jp (K.K.); takashikosone@ 123456gmail.com (T.K.); htakagi@ 123456kusunoki-hp.com (H.T.)
                [2 ]Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan; kakizaki@ 123456gunma-u.ac.jp (S.K.); uraoka@ 123456gunma-u.ac.jp (T.U.)
                Author notes
                [* ]Correspondence: satoken@ 123456gunma-u.ac.jp
                Author information
                https://orcid.org/0000-0002-4366-1699
                https://orcid.org/0000-0002-3202-7983
                https://orcid.org/0000-0003-0224-7093
                https://orcid.org/0000-0002-4425-4331
                Article
                biomedicines-09-00660
                10.3390/biomedicines9060660
                8227298
                fc03c085-f67c-4592-bb1c-8e36a254261b
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 20 April 2021
                : 03 June 2021
                Categories
                Article

                mac-2 binding protein glycosylation isomer,direct acting antivirals,liver fibrosis,hepatocarcinogenesis,sustained virological response

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