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      Homeostatic Model Assessment of Insulin Resistance for Predicting the Recurrence of Hepatocellular Carcinoma after Curative Treatment

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          Abstract

          Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the impact of the disorder of glucose metabolism on the recurrence of HCC after curative treatment. Two hundred and eleven patients with HCC who received curative treatment in our hospital from 2006 to 2017 were enrolled in this study. Recurrence-free survival was estimated using the Kaplan–Meier method, and the differences between the groups partitioned by the presence or absence of DM and the values of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting immunoreactive insulin (FIRI), and homeostasis model assessment-insulin resistance (HOMA-IR) were evaluated using the log-rank test. There were no significant differences in the recurrence-free survival rate between the patients with and without DM ( p = 0.144), higher and lower levels of HbA1c (≥6.5 and <6.5%, respectively; p = 0.509), FPG (≥126 and <126 mg/dL, respectively; p = 0.143), and FIRI (≥10 and <10 μU/mL, respectively; p = 0.248). However, the higher HOMA-IR group (≥2.3) had HCC recurrence significantly earlier than the lower HOMA-IR group (<2.3, p = 0.013). Moreover, there was a significant difference between the higher and lower HOMA-IR groups without DM ( p = 0.009), and there was no significant difference between those groups with DM ( p = 0.759). A higher HOMA-IR level, particularly in non-diabetic patients, was a significant predictor for HCC recurrence after curative treatment.

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          Most cited references26

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          JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan

          The Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma proposed by the Japan Society of Hepatology was updated in June 2014 at a consensus meeting of the Liver Cancer Study Group of Japan. Three important items have been updated: the surveillance and diagnostic algorithm, the treatment algorithm, and the definition of transarterial chemoembolization (TACE) failure/refractoriness. The most important update to the diagnostic algorithm is the inclusion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a first line surveillance/diagnostic tool. Another significant update concerns removal of the term “lipiodol” from the definition of TACE failure/refractoriness.
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            Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

            Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most frequently occurring types of primary liver cancer and together are among the most common incident cancers worldwide. There are a number of modifiable and nonmodifiable HCC and ICC risk factors that have been reported. A review of the existing literature the epidemiology and risk factors for HCC and ICC was performed. There are a number of major infectious, lifestyle, metabolic, and heritable risk factors for both HCC and ICC. Some of these risk factors are either potentially preventable (eg, alcohol and tobacco use) or are currently treatable (eg hepatitis infection). In most cases, the molecular pathway or mechanism by which these etiologic factors cause primary liver cancer has not been well delineated. However, in nearly all cases, it is believed that a given risk factor causes liver injury and inflammation which results in chronic liver disease. Given the rising prevalence of several common HCC and ICC risk factors in the western world, the best opportunities for improving the care of these patients are either through the prevention of modifiable risk factors that are associated with the development of chronic liver disease or the identification of at risk patients, ensuring they are appropriately screened for the development of primary liver cancer, and initiating treatment early.
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              The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence.

              We conducted a systematic review and a meta-analysis to estimate the magnitude and determinants of association between diabetes and hepatocellular carcinoma (HCC). MEDLINE searches were conducted for published full studies (between January 1966 and February 2005) that provided risk estimates and met criteria concerning the definition of exposure and outcomes. Two investigators independently performed standardized search and data abstraction. Unadjusted and adjusted odds ratios for individual outcomes were obtained or calculated for each study and were synthesized using a random-effects model. A total of 26 studies met our inclusion and exclusion criteria. Among 13 case-control studies, diabetes was associated significantly with HCC in 9 studies (pooled odds ratio, 2.5; 95% confidence interval, 1.8-3.5). Among 13 cohort studies, diabetes was associated significantly with HCC in 7 studies (pooled risk ratio, 2.5; 95% confidence interval, 1.9-3.2). The results were relatively consistent in different populations, different geographic locations, and a variety of control groups. The significant association between HCC and diabetes was independent of alcohol use or viral hepatitis in the 10 studies that examined these factors. Few studies adjusted for diet and obesity. Diabetes is associated with an increased risk for HCC. However, more research is required to examine issues related to the duration and treatment of diabetes, and confounding by diet and obesity.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                30 January 2019
                February 2019
                : 20
                : 3
                : 605
                Affiliations
                Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan; koz@ 123456gifu-u.ac.jp (K.T.); hanai0606@ 123456yahoo.co.jp (T.H.); asue@ 123456gifu-u.ac.jp (A.S.); mshiraki-gif@ 123456umin.ac.jp (Mak.S.); shimim-gif@ 123456umin.ac.jp (Mas.S.)
                Author notes
                [* ]Correspondence: ikenji@ 123456gifu-u.ac.jp ; Tel.: +81-(58)-230-6308; Fax: +81-(58)-230-6310
                Article
                ijms-20-00605
                10.3390/ijms20030605
                6387449
                30704150
                50804697-0e2c-4ce8-8569-a0577345bc4f
                © 2019 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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 December 2018
                : 29 January 2019
                Categories
                Article

                Molecular biology
                hepatocellular carcinoma,recurrence risk,diabetes mellitus,insulin resistance,homeostasis model assessment-insulin resistance (homa-ir)

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