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      Utility of Transient Elastography for the Screening of Liver Disease in Patients with Alpha1-Antitrypsin Deficiency

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          Abstract

          Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. A total of 148 AATD patients were included. Among these, 54.7% were Pi*ZZ and 45.3% were heterozygous for the Z allele. Between 4.9% and 16.5% of patients had abnormal liver enzymes, without differences among genotypes. Liver stiffness measurement (LSM) was significantly higher in Pi*ZZ individuals than in heterozygous Z (5.6 vs. 4.6 kPa; p = 0.001). In total, in 8 (5%) individuals LSM was >7.5 kPa, considered significant liver fibrosis, and ≥10 kPa in 3 (1.9%) all being Pi*ZZ. Elevated liver enzymes were more frequently observed in patients with LSM > 7.5 kPa, but in 5 out of 8 of these patients all liver enzymes were within normal range. In patients with AATD, the presence of abnormal liver enzymes is frequent; however, most of these patients do not present significant liver fibrosis. Transient elastography can help to identify patients with liver fibrosis even with normal liver enzymes and should be performed in all Z-allele carriers to screen for liver disease.

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          Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection.

          Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy. However, many models include tests not readily available, and there are limited data from patients with HIV/hepatitis C virus (HCV) coinfection. We aimed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection. A retrospective analysis of liver histology was performed in 832 patients. Liver fibrosis was assessed via Ishak score; patients were categorized as 0-1, 2-3, or 4-6 and were randomly assigned to training (n = 555) or validation (n = 277) sets. Multivariate logistic regression analysis revealed that platelet count (PLT), age, AST, and INR were significantly associated with fibrosis. Additional analysis revealed PLT, age, AST, and ALT as an alternative model. Based on this, a simple index (FIB-4) was developed: age ([yr] x AST [U/L]) / ((PLT [10(9)/L]) x (ALT [U/L])(1/2)). The AUROC of the index was 0.765 for differentiation between Ishak stage 0-3 and 4-6. At a cutoff of 3.25 had a positive predictive value of 65% and a specificity of 97%. Using these cutoffs, 87% of the 198 patients with FIB-4 values outside 1.45-3.25 would be correctly classified, and liver biopsy could be avoided in 71% of the validation group. In conclusion, noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients.
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            EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis.

            (2015)
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              Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.

              The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                16 April 2021
                April 2021
                : 10
                : 8
                : 1724
                Affiliations
                [1 ]Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; monica_xina@ 123456hotmail.com (M.P.); jgenesca@ 123456vhebron.net (J.G.)
                [2 ]Pneumology Department, Hospital Universitari Vall d’Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; alexagnd01@ 123456hotmail.com (A.N.); crise4@ 123456hotmail.com (C.E.); irbelmu@ 123456gmail.com (I.B.); estherod@ 123456vhebron.net (E.R.); mbarrech@ 123456vhebron.net (M.B.)
                [3 ]Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
                [4 ]Pneumology Department, University Hospital Complex of Vigo, Instituto de Investigación Biomédica Galicia Sur, 36213 Vigo, Spain; mtordur@ 123456yahoo.es (M.T.-D.); ramon.antonio.tubio.perez@ 123456sergas.es (R.T.-P.)
                [5 ]Pneumology Department, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico de San Carlos, Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain; jlrhermosa@ 123456yahoo.es (J.L.R.-H.); mcallerubio@ 123456gmail.com (M.C.)
                [6 ]Department of Clinical Biochemistry, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; frarodri@ 123456gmail.com
                [7 ]Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
                [8 ]Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
                Author notes
                [* ]Correspondence: marcm@ 123456separ.es
                [†]

                Both authors have contributed equally and should be considered first authors.

                Author information
                https://orcid.org/0000-0002-0985-3320
                https://orcid.org/0000-0003-0552-2484
                https://orcid.org/0000-0002-3890-2742
                https://orcid.org/0000-0002-1315-4514
                https://orcid.org/0000-0001-8572-5198
                https://orcid.org/0000-0002-9850-9520
                Article
                jcm-10-01724
                10.3390/jcm10081724
                8073267
                33923569
                772b04ae-5977-40a0-9f4a-72504b838be0
                © 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
                : 05 March 2021
                : 13 April 2021
                Categories
                Article

                alpha1-antitrypsin deficiency,liver disease,transient elastography

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