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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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.864550/full |
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| author | Daniel V. DiGiacomo Jessica E. Shay Rory Crotty Nancy Yang Patricia Bloom Kathleen Corey Sara Barmettler Jocelyn R. Farmer |
| author_facet | Daniel V. DiGiacomo Jessica E. Shay Rory Crotty Nancy Yang Patricia Bloom Kathleen Corey Sara Barmettler Jocelyn R. Farmer |
| author_sort | Daniel V. DiGiacomo |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T22:50:29Z |
| format | Article |
| id | doaj.art-0d9e33d9a729440095958794f613249e |
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| language | English |
| last_indexed | 2024-12-11T22:50:29Z |
| publishDate | 2022-05-01 |
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| spelling | doaj.art-0d9e33d9a729440095958794f613249e2022-12-22T00:47:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.864550864550Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative HyperplasiaDaniel V. DiGiacomo0Jessica E. Shay1Rory Crotty2Nancy Yang3Patricia Bloom4Kathleen Corey5Sara Barmettler6Jocelyn R. Farmer7Department of Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Pathology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, United StatesDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, United StatesNodular 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.864550/fullcommon variable immunodeficiency (CVID)nodular regenerative hyperplasia (NRH)transient elastography (TE)fibroscan©liver diseaseliver biopsy |
| spellingShingle | Daniel V. DiGiacomo Jessica E. Shay Rory Crotty Nancy Yang Patricia Bloom Kathleen Corey Sara Barmettler Jocelyn R. Farmer Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia Frontiers in Immunology common variable immunodeficiency (CVID) nodular regenerative hyperplasia (NRH) transient elastography (TE) fibroscan© liver disease liver biopsy |
| 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 | common variable immunodeficiency (CVID) nodular regenerative hyperplasia (NRH) transient elastography (TE) fibroscan© liver disease liver biopsy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.864550/full |
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