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Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia

Nodular regenerative hyperplasia (NRH) is associated with high morbidity and mortality in patients with common variable immunodeficiency (CVID). While liver biopsy is the gold standard for NRH diagnosis, a non-invasive technique could facilitate early disease recognition, monitoring, and/or immune i...

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Autores principales: DiGiacomo, Daniel V., Shay, Jessica E., Crotty, Rory, Yang, Nancy, Bloom, Patricia, Corey, Kathleen, Barmettler, Sara, Farmer, Jocelyn R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121126/
https://www.ncbi.nlm.nih.gov/pubmed/35603209
http://dx.doi.org/10.3389/fimmu.2022.864550
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author DiGiacomo, Daniel V.
Shay, Jessica E.
Crotty, Rory
Yang, Nancy
Bloom, Patricia
Corey, Kathleen
Barmettler, Sara
Farmer, Jocelyn R.
author_facet DiGiacomo, Daniel V.
Shay, Jessica E.
Crotty, Rory
Yang, Nancy
Bloom, Patricia
Corey, Kathleen
Barmettler, Sara
Farmer, Jocelyn R.
author_sort DiGiacomo, Daniel V.
collection PubMed
description Nodular regenerative hyperplasia (NRH) is associated with high morbidity and mortality in patients with common variable immunodeficiency (CVID). While liver biopsy is the gold standard for NRH diagnosis, a non-invasive technique could facilitate early disease recognition, monitoring, and/or immune intervention. We performed a cross-sectional analysis of ultrasound-based transient elastography (TE) in patients with CVID to evaluate liver stiffness and compared this between patients with (N = 12) and without (N = 6) biopsy-proven NRH. Additionally, these data were compared to a cohort followed at our institution for non-alcoholic fatty liver disease (NAFLD) (N = 527), a disease for which TE has routine diagnostic use. Clinical and pathologic features of NRH were evaluated as correlates of liver stiffness, and receiver operating characteristic curves were used to define a liver stiffness cutoff with diagnostic utility for NRH among CVID patients. CVID patients with NRH had a more severe disease presentation compared to those without. This included increased autoinflammatory disease comorbidities, combined B-cell and T-cell dysfunction, and abnormal liver biochemistries (specifically an increased mean alkaline phosphatase level [proximal to TE, 250 vs. 100 U/L; p = 0.03; peak, 314 vs. 114 U/L; p = 0.02). Results of TE demonstrated a significantly elevated liver stiffness in CVID patients with NRH (mean 13.2 ± 6.2 kPa) as compared to both CVID patients without NRH (mean 4.6 ± 0.9 kPa) and non-CVID patients with NAFLD (mean 6.9 ± 5.5 kPa) (p < 0.01). No single or composite histopathologic feature of NRH correlated with liver stiffness including nodule size, nodule density, sinusoidal dilation, fibrosis, and/or lymphocytosis. In contrast, liver stiffness by TE was significantly correlated with clinical parameters of portal hypertension, including an elevated hepatic venous pressure gradient, an increased splenic longitudinal diameter, presence of varices, and presence of peripheral edema. A liver stiffness of greater than or equal to 6.2 kPa was a clinically significant cutoff for NRH in CVID patients. We propose that TE has diagnostic utility in CVID, particularly in the presence of immunophenotypic features such as combined B-cell and T-cell dysfunction, autoinflammatory comorbidities, and/or abnormal liver tests. Elevated liver stiffness by TE should raise suspicion for NRH in patients with CVID and prompt expedited evaluation by hepatology.
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spelling pubmed-91211262022-05-21 Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia DiGiacomo, Daniel V. Shay, Jessica E. Crotty, Rory Yang, Nancy Bloom, Patricia Corey, Kathleen Barmettler, Sara Farmer, Jocelyn R. Front Immunol Immunology Nodular regenerative hyperplasia (NRH) is associated with high morbidity and mortality in patients with common variable immunodeficiency (CVID). While liver biopsy is the gold standard for NRH diagnosis, a non-invasive technique could facilitate early disease recognition, monitoring, and/or immune intervention. We performed a cross-sectional analysis of ultrasound-based transient elastography (TE) in patients with CVID to evaluate liver stiffness and compared this between patients with (N = 12) and without (N = 6) biopsy-proven NRH. Additionally, these data were compared to a cohort followed at our institution for non-alcoholic fatty liver disease (NAFLD) (N = 527), a disease for which TE has routine diagnostic use. Clinical and pathologic features of NRH were evaluated as correlates of liver stiffness, and receiver operating characteristic curves were used to define a liver stiffness cutoff with diagnostic utility for NRH among CVID patients. CVID patients with NRH had a more severe disease presentation compared to those without. This included increased autoinflammatory disease comorbidities, combined B-cell and T-cell dysfunction, and abnormal liver biochemistries (specifically an increased mean alkaline phosphatase level [proximal to TE, 250 vs. 100 U/L; p = 0.03; peak, 314 vs. 114 U/L; p = 0.02). Results of TE demonstrated a significantly elevated liver stiffness in CVID patients with NRH (mean 13.2 ± 6.2 kPa) as compared to both CVID patients without NRH (mean 4.6 ± 0.9 kPa) and non-CVID patients with NAFLD (mean 6.9 ± 5.5 kPa) (p < 0.01). No single or composite histopathologic feature of NRH correlated with liver stiffness including nodule size, nodule density, sinusoidal dilation, fibrosis, and/or lymphocytosis. In contrast, liver stiffness by TE was significantly correlated with clinical parameters of portal hypertension, including an elevated hepatic venous pressure gradient, an increased splenic longitudinal diameter, presence of varices, and presence of peripheral edema. A liver stiffness of greater than or equal to 6.2 kPa was a clinically significant cutoff for NRH in CVID patients. We propose that TE has diagnostic utility in CVID, particularly in the presence of immunophenotypic features such as combined B-cell and T-cell dysfunction, autoinflammatory comorbidities, and/or abnormal liver tests. Elevated liver stiffness by TE should raise suspicion for NRH in patients with CVID and prompt expedited evaluation by hepatology. Frontiers Media S.A. 2022-05-06 /pmc/articles/PMC9121126/ /pubmed/35603209 http://dx.doi.org/10.3389/fimmu.2022.864550 Text en Copyright © 2022 DiGiacomo, Shay, Crotty, Yang, Bloom, Corey, Barmettler and Farmer https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
DiGiacomo, Daniel V.
Shay, Jessica E.
Crotty, Rory
Yang, Nancy
Bloom, Patricia
Corey, Kathleen
Barmettler, Sara
Farmer, Jocelyn R.
Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia
title Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia
title_full Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia
title_fullStr Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia
title_full_unstemmed Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia
title_short Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia
title_sort liver stiffness by transient elastography correlates with degree of portal hypertension in common variable immunodeficiency patients with nodular regenerative hyperplasia
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121126/
https://www.ncbi.nlm.nih.gov/pubmed/35603209
http://dx.doi.org/10.3389/fimmu.2022.864550
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