Liver fibrosis is associated with arterial calcification (AC). Since the liver is a source of inorganic pyrophosphate (PPi), an anti-calcifying compound, we investigated the relationship between plasma PPi ([PPi]pl), liver fibrosis, liver function, AC, and the hepatic expression of genes regulating PPi homeostasis. To that aim, we compared [PPi]pl before liver transplantation (LT) and 3 months after LT. We also assessed the expression of four key regulators of PPi in liver tissues and established correlations between AC, and scores of liver fibrosis and liver failure in these patients. LT candidates with various liver diseases were included. AC scores were assessed in coronary arteries, abdominal aorta, and aortic valves. Liver fibrosis was evaluated on liver biopsies and from non-invasive tests (FIB-4 and APRI scores). Liver functions were assessed by measuring serum albumin, ALBI, MELD, and Pugh–Child scores. An enzymatic assay was used to dose [PPi]pl. A group of patients without liver alterations from a previous cohort provided a control group. Gene expression assays were performed with mRNA extracted from liver biopsies and compared between LT recipients and the control individuals. [PPi]pl negatively correlated with APRI (r = −0.57, p = 0.001, n = 29) and FIB-4 (r = −0.47, p = 0.006, n = 29) but not with interstitial fibrosis index from liver biopsies (r = 0.07, p = 0.40, n = 16). Serum albumin positively correlated with [PPi]pl (r = 0.71; p < 0.0001, n = 20). ALBI, MELD, and Pugh–Child scores correlated negatively with [PPi]pl (r = −0.60, p = 0.0005; r = −0.56, p = 0.002; r = −0.41, p = 0.02, respectively, with n = 20). Liver fibrosis assessed on liver biopsies by FIB-4 and by APRI positively correlated with coronary AC (r = 0.51, p = 0.02, n = 16; r = 0.58, p = 0.009, n = 20; r = 0.41, p = 0.04, n = 20, respectively) and with abdominal aorta AC (r = 0.50, p = 0.02, n = 16; r = 0.67, p = 0.002, n = 20; r = 0.61, p = 0.04, n = 20, respectively). FIB-4 also positively correlated with aortic valve calcification (r = 0.40, p = 0.046, n = 20). The key regulator genes of PPi production in liver were lower in patients undergoing liver transplantation as compared to controls. Three months after surgery, serum albumin levels were restored to physiological levels (40 [37–44] vs. 35 [30–40], p = 0.009) and [PPi]pl was normalized (1.40 [1.07–1.86] vs. 0.68 [0.53–0.80] µmol/L, p = 0.0005, n = 12). Liver failure and/or fibrosis correlated with AC in several arterial beds and were associated with low plasma PPi and dysregulation of key proteins involved in PPi homeostasis. Liver transplantation normalized these parameters.

Purpose: In coronavirus disease 2019 (COVID-19) patients, clinical manifestations as well as chest CT lesions are variable. Lung scintigraphy allows to assess and compare the regional distribution of ventilation and perfusion throughout the lungs. Our main objective was to describe ventilation and perfusion injury by type of chest CT lesions of COVID-19 infection using V/Q SPECT/CT imaging. Patients and Methods: We explored a national registry including V/Q SPECT/CT performed during a proven acute SARS-CoV-2 infection. Chest CT findings of COVID-19 disease were classified in 3 elementary lesions: ground-glass opacities, crazy-paving (CP), and consolidation. For each type of chest CT lesions, a semiquantitative evaluation of ventilation and perfusion was visually performed using a 5-point scale score (0 = normal to 4 = absent function). Results: V/Q SPECT/CT was performed in 145 patients recruited in 9 nuclear medicine departments. Parenchymal lesions were visible in 126 patients (86.9%). Ground-glass opacities were visible in 33 patients (22.8%) and were responsible for minimal perfusion impairment (perfusion score [mean ± SD], 0.9 ± 0.6) and moderate ventilation impairment (ventilation score, 1.7 ± 1); CP was visible in 43 patients (29.7%) and caused moderate perfusion impairment (2.1 ± 1.1) and moderate-to-severe ventilation impairment (2.5 ± 1.1); consolidation was visible in 89 patients (61.4%) and was associated with moderate perfusion impairment (2.1 ± 1) and severe ventilation impairment (3.0 ± 0.9). Conclusions: In COVID-19 patients assessed with V/Q SPECT/CT, a large proportion demonstrated parenchymal lung lesions on CT, responsible for ventilation and perfusion injury. COVID-19–related pulmonary lesions were, in order of frequency and functional impairment, consolidations, CP, and ground-glass opacity, with typically a reverse mismatched or matched pattern.

Purpose: The COVID-19 pandemic has left many survivors with persistent respiratory symptoms such as dyspnea, chronic cough, and reduced exercise capacity. Fibrosis-like abnormalities on high-resolution CT are frequently reported in theses patient. This study aimed to describe the morphological pulmonary abnormalities identified on V/Q SPECT/CT after COVID-19 infection and to evaluate their functional consequences on regional ventilation and perfusion. We also sought to identify clinical predictors of abnormal V/Q SPECT/CT findings. Methods: This retrospective multicenter study was based on a national registry of patients referred for V/Q SPECT/CT because of persistent respiratory symptoms after COVID-19 infection. CT abnormalities were characterized using standard radiological criteria. Ventilation and perfusion were visually graded using a five-point scale. Clinical, demographic, and acute COVID-19 characteristics were analyzed to identify predictors of abnormal imaging. Results: Among the 217 included patients (mean age 58 ± 15 years), 122 (56%) presented pulmonary abnormalities on V/Q SPECT or CT. The most frequent parenchymal abnormalities were reticulations, consolidations, atelectasis, emphysema, and ground-glass opacities. Emphysema, consolidations, and fibrosis were associated with the most severe impairments of both ventilation and perfusion. Age and pre-existing chronic lung disease were the strongest predictors of abnormal imaging, while a mild acute COVID-19 course without oxygen therapy was protective. Conclusion: V/Q SPECT/CT provides a comprehensive structural and functional assessment of long COVID pulmonary sequelae. It allows the differentiation between reversible inflammatory lesions and persistent structural abnormalities with lasting functional consequences.