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Magaz M, Alvarez-Larrán A, Colomer D, et al. Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis. J Hepatol. 2020;74(1):89-95doi: 10.1016/j.jhep.2020.06.045.
Magaz, M., Alvarez-Larrán, A., Colomer, D., López-Guerra, M., García-Criado, M. �. �., Mezzano, G., Belmonte, E., Olivas, P., Soy, G., Cervantes, F., Darnell, A., Ferrusquía-Acosta, J., Baiges, A., Turon, F., Hernández-Gea, V., & García-Pagán, J. C. (2021). Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis. Journal of hepatology, 74(1), 89-95. https://doi.org/10.1016/j.jhep.2020.06.045
Magaz, Marta, et al. "Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis." Journal of hepatology vol. 74,1 (2021): 89-95. doi: https://doi.org/10.1016/j.jhep.2020.06.045
Magaz M, Alvarez-Larrán A, Colomer D, López-Guerra M, García-Criado MÁ, Mezzano G, Belmonte E, Olivas P, Soy G, Cervantes F, Darnell A, Ferrusquía-Acosta J, Baiges A, Turon F, Hernández-Gea V, García-Pagán JC. Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis. J Hepatol. 2021 Jan;74(1):89-95. doi: 10.1016/j.jhep.2020.06.045. Epub 2020 Jul 15. PMID: 32679300.
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J Hepatol. 2021 Jan;74(1):89-95. doi: 10.1016/j.jhep.2020.06.045. Epub 2020 Jul 15.

Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis.

Journal of hepatology

Marta Magaz, Alberto Alvarez-Larrán, Dolors Colomer, Mónica López-Guerra, M Ángeles García-Criado, Gabriel Mezzano, Ernest Belmonte, Pol Olivas, Guillem Soy, Francisco Cervantes, Anna Darnell, José Ferrusquía-Acosta, Anna Baiges, Fanny Turon, Virginia Hernández-Gea, Juan Carlos García-Pagán

Affiliations

  1. Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut de Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Health Care Provider of the European Reference Network on Rare Liver Disorders, Barcelona, Spain.
  2. Hematology Department, Hospital Clinic, Institut de Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
  3. Hematopathology Section, Pathology Department, Hospital Clinic, Institut de Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red en Cancer, University of Barcelona, Barcelona, Spain.
  4. Abdominal Radiology Section, Radiology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain.
  5. Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut de Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Health Care Provider of the European Reference Network on Rare Liver Disorders, Barcelona, Spain. Electronic address: [email protected].

PMID: 32679300 DOI: 10.1016/j.jhep.2020.06.045

Abstract

BACKGROUND & AIMS: Myeloproliferative neoplasms (MPNs) are the most frequent cause of non-tumoural non-cirrhotic splanchnic vein thrombosis (NC-SVT). Diagnosis of MPN is based on blood cell count alterations, bone marrow histology, and detection of specific gene mutations. Next-generation sequencing (NGS) allows the simultaneous evaluation of multiple genes implicated in myeloid clonal pathology. The aim of this study was to evaluate the potential role of NGS in elucidating the aetiology of NC-SVT.

METHODS: DNA samples from 80 patients (75 with idiopathic or exclusively local factor [Idiop/loc-NC-SVT] and 5 with MPN and NC-SVT [SVT-MPN] negative for Janus kinase 2 gene [JAK2] [V617F and exon 12], calreticulin gene [CALR], and thrombopoietin gene [MPL] mutations by classic techniques) were analysed by NGS. Mutations involved in myeloid disorders different from JAK2, CALR, and MPL genes were categorised as high-molecular-risk (HMR) variants or variants of unknown significance.

RESULTS: In 2/5 triple-negative SVT-MPN cases (40%), a mutation in exon 12 of JAK2 was identified. JAK2-exon 12 mutation was also identified in 1/75 patients with Idiop/loc-NC-SVT. Moreover, 28/74 (37.8%) of the remaining Idiop/loc-NC-SVT had at least 1 HMR variant. Sixty-two patients with Idiop/loc-NC-SVT were not receiving long-term anticoagulation and 5 of them (8.1%) had recurrent NC-SVT. This cumulative incidence was significantly higher in patients with HMR variants than in those without.

CONCLUSIONS: NGS identified JAK2-exon12 mutations not previously detected by conventional techniques. In addition, NGS detected HMR variants in approximately one-third of patients with Idiop/loc-NC-SVT. These patients seem to have a higher risk of splanchnic rethrombosis. NGS might be a useful diagnostic tool in NC-SVT.

LAY SUMMARY: Next-generation sequencing (NGS) performs massive sequencing of DNA allowing the simultaneous evaluation of multiple genes even at very low mutational levels. Application of this technique in a cohort of patients with non-cirrhotic non-tumoral portal vein thrombosis (NC-SVT) and a negative study for thrombophilic disorders was able to identify patients with a mutation in exon 12 not previously detected by conventional techniques. Moreover, NGS detected High Molecular Risk (HMR)-variants (Mutations involved in myeloid disorders different from JAK2, CALR and MPL genes) in approximately one third of patients. These patients appear to be at increased risk of rethrombosis. All these findings supports NGS as a potential useful tool in the management of NC-SVT.

Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Keywords: Budd-Chiari syndrome; Myeloproliferative neoplasms; NGS (next-generation sequencing); Non-cirrhotic splanchnic vein thrombosis; Portal vein thrombosis

Conflict of interest statement

Conflicts of interest Virginia Hernández-Gea receives speaker fees from Gore. Juan Carlos García-Pagán reports from W. L. Gore and Associates, Cook Medical, Shionogi, and Vifor Pharma, and receives gr

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