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      Liver stiffness measurement predicted liver‐related events and all‐cause mortality: A systematic review and nonlinear dose–response meta‐analysis

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          Abstract

          Numerous studies have investigated the prognosis value of the liver stiffness measurement (LSM) by transient elastography in assessing the risk of liver‐related events (LREs) and all‐cause mortality in patients with chronic liver disease (CLD). However, the shape of the dose–response relationship between them remains unclear. We searched PubMed, Embase, the Cochrane Library, and reference lists of articles for studies published up to July 1, 2017, that assessed the LSM in predicting LREs and all‐cause mortality among subjects with CLD. Fifty‐four observational cohort studies with 35,249 participants were included. Summary relative risks (RRs) were calculated using a random‐effects model, and a restricted cubic spline function was used to model the dose–response association. LREs and all‐cause mortality were increased in subjects with a high LSM (LRE: RR, 7.90; 95% confidence interval [CI], 5.65, 11.05; I 2 = 71.6%; all‐cause mortality: RR, 4.15; 95% CI, 2.56, 6.72; I 2 = 68.5%). For each unit increment of liver stiffness, the summary RR was 1.06 (95% CI, 1.06, 1.07; I 2 = 74.6%) for LREs and 1.06 (95% CI, 1.04, 1.07; I 2 = 55.7%) for all‐cause mortality. A positive relationship with a nonlinear trend for LSM with LREs and all‐cause mortality was examined by a dose–response meta‐analysis ( P < 0.001). When stratified by etiology, a nonlinear association was also found in patients infected with hepatitis C virus and those coinfected with hepatitis C virus and human immunodeficiency virus. In contrast, there was no evidence of departure from linearity among patients with hepatitis B virus infection ( P nonlinearity = 0.072). Conclusion: LSM is useful in screening LREs and all‐cause mortality in patients with CLD. Further studies are warranted in assessing the application of LSM in monitoring the risk of LREs and all‐cause mortality in clinical practice. ( Hepatology Communications 2018;2:467‐476)

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          Flexible meta-regression functions for modeling aggregate dose-response data, with an application to alcohol and mortality.

          In this paper, the authors describe fractional polynomials and cubic splines with which to represent smooth dose-response relations in summarizing meta-analytical aggregate data. Use of these two curve-fitting families can help prevent the problems arising from inappropriate linearity assumptions. These methods are illustrated in the problem of estimating the shape of the dose-response curve between alcohol consumption and all-cause mortality risk. The authors considered aggregate data from 29 cohort studies investigating this issue (1966-2000). J-shaped curves with a nadir at approximately 5-7 g/day of alcohol consumption and a last protective dose of 47-60 g/day were consistently obtained from fractional polynomials and cubic splines. The authors conclude that both of the curve-fitting families are useful tools with which to explore dose-response epidemiologic questions by means of meta-analytical approaches, especially when important nonlinearity is anticipated.
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            Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases.

            A proper diagnosis of cirrhosis is essential for the management of patients with chronic liver diseases. We assessed the accuracy of liver stiffness measurement by Fibroscan for the diagnosis of cirrhosis in 1,257 patients with chronic liver diseases of various causes enrolled in a prospective multicenter study as well as clarified causes of discrepancies between liver histology and Fibroscan. One hundred thirty-two patients had unsuitable biopsy specimens, and 118 had unreliable liver stiffness measurements. Because 232 patients overlapped with a previous study, analysis was performed in the 775 new patients then derived in the whole population (1,007; 165 cirrhosis). Diagnostic accuracy was assessed by receiver operator curve (ROC) analysis. Liver samples were re-analyzed in case of discrepancies. The area under the ROC (AUROC) was 0.95 (95% CI, 0.93-0.96) for the diagnosis of cirrhosis in either 775 or 1,007 patients. The cutoff value with optimal diagnosis accuracy was 14.6 kPa in 1,007 patients (positive and negative predictive values, 74% and 96%) with discrepancies among the etiological groups. Eighty patients were misclassified: (1) among 45 patients without cirrhosis with liver stiffness 14.6 kPa or greater, 27 (60%) had extensive fibrosis and 10 (22%) significant perisinusoidal fibrosis; and (2) among 35 patients with cirrhosis and liver stiffness less than 14.6 kPa, 10 (29%) had a macronodular pattern and 25 (71%) either none or mild activity. In conclusion, Fibroscan is a reliable method for the diagnosis of cirrhosis in patients with chronic liver diseases, better at excluding than at predicting cirrhosis using a threshold of 14.6 kPa. False-negatives are mainly attributable to inactive or macronodular cirrhosis.
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              Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta-analysis.

              Liver stiffness measurement (LSM), using elastography, can independently predict outcomes of patients with chronic liver diseases (CLDs). However, there is much variation in reporting and consistency of findings. We performed a systematic review and meta-analysis to evaluate the association between LSM and outcomes of patients with CLDs. We performed a systematic review of the literature, through February 2013, for studies that followed up patients with CLDs prospectively for at least 6 months and reported the association between baseline LSM and subsequent development of decompensated cirrhosis or hepatocellular carcinoma (HCC), as well as mortality. Summary relative risk (RR) estimates per unit of LSM and 95% confidence intervals (CIs) were estimated using the random effects model. Our final analysis included 17 studies, reporting on 7058 patients with CLDs. Baseline LSM was associated significantly with risk of hepatic decompensation (6 studies; RR, 1.07; 95% CI, 1.03-1.11), HCC (9 studies; RR, 1.11; 95% CI, 1.05-1.18), death (5 studies; RR, 1.22; 95% CI, 1.05-1.43), or a composite of these outcomes (7 studies; RR, 1.32; 95% CI, 1.16-1.51). We observed considerable heterogeneity among studies-primarily in the magnitude of effect, rather than the direction of effect. This heterogeneity could not be explained by variations in study locations, etiologies and stages of CLD, techniques to measure liver stiffness, adjustment for covariates, or method of imputing relationship in the meta-analysis. Based on a meta-analysis of cohort studies, the degree of liver stiffness is associated with risk of decompensated cirrhosis, HCC, and death in patients with CLDs. LSM therefore might be used in risk stratification. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                wenxiang_huang@163.com
                Journal
                Hepatol Commun
                Hepatol Commun
                10.1002/(ISSN)2471-254X
                HEP4
                Hepatology Communications
                John Wiley and Sons Inc. (Hoboken )
                2471-254X
                13 February 2018
                April 2018
                : 2
                : 4 ( doiID: 10.1002/hep4.v2.4 )
                : 467-476
                Affiliations
                [ 1 ] Department of Infectious Diseases First Affiliated Hospital of Chongqing Medical University Chongqing China
                [ 2 ] Department of Science and Education First People's Hospital of Changde City Hunan China
                [ 3 ] Department of Gerontology Second Affiliated Hospital of Chongqing Medical University Chongqing China
                [ 4 ] Department of Radiology First Affiliated Hospital of Chongqing Medical University Chongqing China
                [ 5 ] Department of Hepatobiliary Surgery Second Affiliated Hospital of Chongqing Medical University Chongqing China
                Author notes
                [*] [* ] ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:

                Wenxiang Huang, M.D.

                Department of Infectious Diseases

                First Affiliated Hospital of Chongqing Medical University

                Chongqing, 400016, China

                E‐mail: wenxiang_huang@ 123456163.com

                Tel: +86‐138‐8353‐3808

                Article
                HEP41154
                10.1002/hep4.1154
                5880200
                956bf973-3181-4caa-8e9c-6385f3913dd5
                © 2018 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 10 October 2017
                : 15 December 2017
                : 11 January 2018
                Page count
                Figures: 2, Tables: 1, Pages: 10, Words: 5303
                Funding
                Funded by: Chongqing Science Foundation
                Award ID: KJ130332
                Categories
                Special Article
                Special Article
                Custom metadata
                2.0
                hep41154
                April 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.4 mode:remove_FC converted:02.04.2018

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