3-Fr steerable microcatheter system via the upper limb artery in RADPLAT for right maxillary cancer.

BACKGROUND: To evaluate the efficacy of a catheter system using a 3-Fr sheath with a steerable microcatheter through right upper limb artery access for superselective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) to treat right maxillary sinus squamous cell carcinoma (MS-SCC). MATERIAL AND METHODS: We retrospectively studied 46 sessions in eight patients treated between November 2020 and February 2023 using the catheter system briefly described below. A 3-Fr sheath was inserted into the distal radial, conventional radial, or brachial arteries. A coaxial catheter system with a 2.9-Fr steerable microcatheter and a 1.9-Fr microcatheter was advanced into the brachiocephalic artery. The right common carotid artery was selected by bending the tip of the steerable microcatheter. Coil embolization and intra-arterial cisplatin infusion after selecting each external carotid artery branch were achieved using this catheter system. RESULTS: Cisplatin infusion and coil embolization were successful in all sessions. Arterial occlusion at the sheath insertion sites was found in 29.4% (5/17) of the distal radial arteries and 33.3% (3/9) of the conventional radial arteries. No other major complications were observed during the procedure. CONCLUSION: Using a 3-Fr catheter system with a steerable microcatheter through right upper limb artery access is a feasible method for RADPLAT in treating right MS-SCC.

Apolipoprotein E-containing lipoproteins and their extracellular interactions with LRP1 affect LPS-induced inflammation.

The linkage between low-density lipoprotein receptor-related protein (LRP)1-mediated metabolism of apolipoprotein (apo) E-containing lipoproteins (apoE-LP) and the lipopolysaccharide (LPS)-induced inflammatory response contributes to the pathogenesis of sepsis; however, the underlying mechanisms are unclear. Therefore, in this study, the effects of apoE-LP and their constituents on the mRNA expression of interleukin (IL)-6 and LRP1 were evaluated using a culture system of human fibroblasts supplemented with LPS and apoE-containing emulsion particles (apoE-EP). The affinity of apoE-LP for LPS was examined using the interaction between fluorescence-labeled LPS and serum lipoprotein fractions. LPS-induced inflammation significantly upregulated the mRNA expression of IL-6 and LRP1. This upregulation was markedly suppressed by pre-incubation of LPS with apoE-EP or its constituents (apoE or EP). The suppressive effect of apoE-EP on IL-6 upregulation was attenuated in the presence of lactoferrin, an inhibitor of LRP1. The prepared apoE-EP and serum triglyceride-rich lipoproteins showed significant affinity for LPS. However, these affinities appeared to be lower than expected based on the extent to which IL-6 upregulation was suppressed by pre-incubation of LPS with apoE-EP. Overall, these results indicate that LPS-induced inflammation may be regulated by 1) the LPS-neutralizing effect of apoE-LP, 2) anti-inflammatory effect of apoE, and 3) LRP1-mediated metabolic pathways.

Thyrolinguofacial trunk arising from the common carotid artery and diagnosed by computed tomography angiography.

PURPOSE: Various variations in the head and neck vasculature have been reported. The purpose of this report is to describe an extremely rare case of thyrolinguofacial trunk (TLFT) arising from the common carotid artery (CCA). METHODS: A 66-year-old woman with vertigo, dizziness, and heaviness in the head underwent computed tomography (CT) angiography of the neck and head region for evaluation of cerebrovascular diseases. RESULTS: The TLFT originated from the anterior wall of the right CCA and was divided into the superior thyroid artery and linguofacial trunk (LFT). The LFT was divided into lingual and facial arteries. In addition, we observed fusiform dilatation of the intracranial right vertebral artery, which might have caused these symptoms. CONCLUSION: The presence of a common trunk of the external carotid artery (ECA) branches increases the risk of complications such as bleeding and ischemia during treatment of the head and neck region, including chemoradiotherapy for oral bleeding and tongue cancer. Therefore, this is an area of significant interest across various medical specialties, including surgery, otolaryngology, and radiology. Understanding the diverse variations in the neck vasculature is expected to lead to a reduction in complications associated with various procedures.

Characterization of novel truncated apolipoprotein A-I in human high-density lipoprotein generated by sequential treatment with myeloperoxidase and chymase.

High-density lipoprotein (HDL) cholesterol is a well-known biomarker, which has been associated with reduction in the risk of cardiovascular diseases (CVD). However, some HDL anti-atherosclerotic functions may be impaired without altered HDL-cholesterol (HDL-C) level via its dysfunctional proteins or other physiological reactions in vivo. We previously showed that activated mast cell-derived chymase could modestly cleave apolipoprotein A-I (apoA-I) in HDL3, and further easily cleave lipid-free apoA-I. In contrast, myeloperoxidase (MPO) secreted by macrophages, the main cell type in atherosclerotic plaques, could oxidize HDL proteins, which might modify their tertiary structures, increasing their susceptibility to other enzymes. Here we focused on the co-modification and impact of chymase and MPO, usually secreted during inflammation from cells with possible co-existence in atheromas, on HDL. Only after sequential treatment with MPO and then chymase, two novel truncated apoA-I fragments were generated from HDL. One fragment was 16.5 kDa, and the cleavage site by chymase after MPO modification was the C-terminal of Tyr100 in apoA-I, cross-validated by three different mass spectrometry methods. This novel apoA-I fragment can be trapped in HDL particles to avoid kidney glomerular filtration and has a specific site for antibody generation for ELISA tests. As such, its quantification can be useful in predicting patients with CVD having normal HDL-C levels.

Neuroendocrine tumor of the breast showing invasive micropapillary features and multiple lymph node metastases.

BACKGROUND: Herein, for the first time, we present a case with mixed invasive micropapillary and neuroendocrine mammary neoplasm. CASE: The patient, a 65-year-old postmenopausal woman, had become aware of a tumor in her right breast 11 months prior to presentation at our hospital. The cut surface of the mastectomy specimen contained a well-circumscribed, multinodular, red-brown tumor, measuring 15x15x15 cm. Histopathologically, this solid cystic lesion consisted of medullary growth of cancer cells accompanied by a well-developed vascular network as well as conspicuous hemorrhage. Cancer cell nests of various sizes displayed an "inside-out" structure surrounded by empty spaces. Most cancer cells were polygonal, though a few were short fusiform-shaped, and possessed finely granular, eosinophilic cytoplasm and ovoid, fine-granular nuclei. Eighteen mitotic figures were observed in 10 high-power fields. Macrometastases, up to 13x8 mm in size, with the same morphological features as the original tumor site, were identified in 3 of 15 dissected right axillary nodes. Immunohistochemically, primary and metastatic cancer cells were diffusely positive for chromogranin A and the estrogen receptor (Allred's total score: 8) and focally reactive for synaptophysin and the progesterone receptor (total score: 5). HER2 and cytokeratin 5/6 were negative, and the MIB-1 labelling index was 36.2%. MUC1 and EMA lined the stroma-facing surfaces of the cell membranes, indicating reversed polarity. CONCLUSION: Our current patient, who had an invasive breast carcinoma with concomitant neuroendocrine and micropapillary features, developed multiple nodal metastases in association with a large-diameter tumor showing a luminal B-like immuno-profile. Accordingly, meticulous clinical follow-up remains essential for this uncommon case.

Basophil activation test for allergic and febrile non-haemolytic transfusion reactions among paediatric patients with haematological or oncological disease.

BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are common, although their mechanisms remain unclear. Immunoglobulin E (IgE)-mediated type I hypersensitivity may be involved in the pathogenesis of ATR. A basophil activation test (BAT) may help elucidate this process. MATERIALS AND METHODS: The BAT was based on peripheral blood samples from paediatric patients with a haematological or oncological disease and on samples of residual blood products transfused in each case. Dasatinib was used to evaluate whether basophil activation was mediated by an IgE-dependent pathway. RESULTS: Twenty-seven patients with and 19 patients without ATR/FNHTR were included in this study, respectively. The median BAT values associated with ATR- (n = 41) and FNHTR-causing (n = 5) blood products were 22.1% (range = 6.1%-77.0%) and 27.8% (range = 15.2%-47.8%), respectively, which were higher than the median value of 8.5% (range = 1.1%-40.9%) observed in blood products without a transfusion reaction. Dasatinib suppressed basophil activity. BAT values were comparable in patients with ATR regardless of severity. Meanwhile, BAT values analysed with blood products non-causal for ATR/FNHTR were higher in patients with ATR/FNHTR than in those without. CONCLUSION: The IgE-mediated type I hypersensitivity may be involved in the pathogenesis of ATR and FNHTR. BAT analyses may help elucidate the underlying mechanisms and identify patients at risk.

Impact of Cytoreductive Nephrectomy Following Nivolumab Plus Ipilimumab Therapy for Patients With Advanced Renal Cell Carcinoma.

BACKGROUND/AIM: CheckMate 214 study revealed that nivolumab plus ipilimumab combination therapy showed a strong and durable effect compared to sunitinib for patients with advanced renal cell carcinoma (aRCC). Most of the patients underwent previous nephrectomy before systemic treatment. We retrospectively investigated the clinical outcomes of Japanese patients treated with cytoreductive nephrectomy following nivolumab plus ipilimumab for aRCC. PATIENTS AND METHODS: Seventy-nine patients were treated with systemic therapy for aRCC between October 2018 and August 2021 at the Saitama Medical University International Medical Center. Ten of 61 patients treated with nivolumab plus ipilimumab underwent cytoreductive nephrectomy after the combined immunotherapy. RESULTS: The median overall survival and progression-free survival were 24.3 and 15.9 months, respectively. The objective response rate was 50.8%; 9.8% of patients had a complete response, and the median time to objective response was 3.2 (range=1.3-19.7) months. The estimated percentage of patients who sustained an objective response at 30 months was 73.0%. Twenty-three patients (74%) in the complete or partial response (CR/PR) group, 11 patients (52%) in the stable disease (SD) group, and two patients (22%) in the progressive disease (PD) group had immune-related adverse events of grade 3 or higher, respectively. For all 10 patients, cytoreductive nephrectomy following nivolumab plus ipilimumab treatment were completed safely. Three patients achieved a pathological complete response without viable cancer cells. Only two patients had residual lesions on images after deferred cytoreductive nephrectomy; the remaining patients achieved radiological CR. CONCLUSION: Cytoreductive nephrectomy after nivolumab plus ipilimumab treatment could be useful in a limited number of cases, possibly resulting in curative nephrectomy due to the durable therapeutic effect of immunotherapy.

Stiff coils enhance shape retention and pressure resistance in an aneurysm model even at low volume.

PURPOSE: To elucidate the characteristics of 3 D frame coils and identify the optimal coil for visceral aneurysms. MATERIAL AND METHODS: Using a vascular model, we compared the postembolization coil distribution and repulsive force of three coils: Guglielmi detachable coil (GDC; stock wire diameter, 0.004 in; primary diameter, 0.015 in), Target XL (0.003, 0.014), and Target XXL (0.003, 0.017). Additionally, the coil area, roundness, and center of gravity were quantitatively compared. The coil repulsive force was measured by compressing the postembolization vessel model with a digital force gauge. RESULTS: There were no significant differences in the coil area and roundness among the three coil types. Compared with the Target coils, the GDC deployed evenly along the vessel wall, its center of gravity was less displaced, and although it had the lowest embolic density, its repulsive force was greater regardless of the number of coils used. CONCLUSIONS: GDC coils with a larger stock wire diameter and a smaller primary diameter unfolded evenly along the wall and had a greater repulsive force. Coil stiffness contributes to coil stability and shape retention, indicating the possibility of preventing recurrence by selecting a frame coil with a focus on coil stiffness.

Quantitative and qualitative lipid improvement with chronic hepatitis C virus eradication using direct-acting antivirals.

AIM: Direct-acting antivirals have revolutionized hepatitis C virus (HCV) therapy by providing a high sustained virological response (SVR) rate and subsequent favorable lipid increases. Proprotein convertase subtilisin-kexin like-9 (PCSK9) plays an important role in regulating quantitative lipid levels. This study examined the interactions between quantitative PCSK9 and lipid changes, as well as qualitative lipid changes in terms of lectin-like oxidized low-density lipoprotein (LDL) receptor-1 ligand containing apolipoprotein B (LAB) and high-density lipoprotein (HDL) cholesterol uptake capacity (HDL-CUC). METHODS: Patients with chronic HCV infection (N = 231) who achieved an SVR by direct-acting antivirals without lipid-lowering therapy were included for comparisons of PCSK9, LAB, HDL-CUC, and other clinical indices between pretreatment and SVR12 time points. RESULTS: LDL (LDL) cholesterol and HDL cholesterol levels were quantitatively increased at SVR12, along with higher PCSK9 (all p < 0.0001). PCSK9 was significantly correlated with LDL cholesterol (r = 0.244, p = 0.0003) and apolipoprotein B (r = 0.222, p = 0.0009) at SVR12. Regarding qualitative LDL changes, LAB was significantly decreased and LAB/LDL cholesterol and LAB/apolipoprotein B proportions were improved at SVR12 (all p < 0.0001). In terms of qualitative HDL changes, HDL-CUC was significantly ameliorated, along with HDL-CUC/HDL cholesterol, HDL-CUC/ apolipoprotein A1, and HDL-CUC/ apolipoprotein A2 at SVR12 (all p < 0.0001). CONCLUSIONS: HCV eradication by direct-acting antivirals may produce quantitative lipid profile changes, along with PCSK9 production recovery in addition to qualitative lipid improvement, which possibly confers the additional secondary benefits of atherosclerosis improvement and cardiovascular disease event reduction.

Cut-off values of serum IgG4 among three reagents, including a novel IgG4 reagent: a multicenter study.

Elevated serum IgG4 is a useful marker of IgG4-related disease (IgG4-RD) activity. However, there is no uniformity in the cut-off values of IgG4 among the various reagents. The aim of this study was to compare the measured and cut-off values of IgG4 assessed using three different reagents. This study enrolled 466 IgG4-RD and non-IgG4-RD patients who required measurement of serum IgG4 levels to diagnose or treat IgG4-RD. Serum IgG4 was measured using three reagents: N-assay LA IgG4 Nittobo (Nittobo), BS-NIA IgG4 (TBS), and N Latex IgG4 (Siemens). The values obtained using the three reagents were compared, and cut-off values were calculated for each. Although there was good correlation among the results with the three reagents, the measured and cut-off values were all different. The Nittobo values were 1.4 times the TBS values and the TBS values were almost half those of the Siemens values. ROC curve analysis showed cut-off values for the Nittobo, TBS, and Siemens reagents of 1.42, 1.31, and 2.38 g/L, respectively. The measured and cut-off values of serum IgG4 vary depending on the reagents used for the assay, although there is good correlation among the values measured by the three reagents.

Changes in serum citrullinated fibrinogen concentration associated with the phase of bacteremia patients.

BACKGROUND: Citrullinated fibrinogen (C-Fbg) has been detected in rheumatoid arthritis; however, few studies have reported the role of C-Fbg in other inflammatory diseases. This study aimed to clarify the changes in serum C-Fbg associated with the bacteremia phase. METHODS: We measured serum C-Fbg concentration in bacteremia patients. C-Fbg levels at each phase of bacteremia, classified by white blood cell (WBC) count and neutrophil left shift change, were compared with those of healthy control (HC). The correlation between C-Fbg concentration and certain inflammatory markers, or citrullinated histone H3 concentration was assessed. Multiple linear regression (MLR) analysis was used to examine the association of log C-Fbg with certain inflammatory markers. RESULT: Serum C-Fbg levels were significantly higher in bacteremia patients than in HC (p < 0.001) and positively correlated with WBC and neutrophil count. Further, C-Fbg levels were significantly higher in phases III and IV of bacteremia than in HC (p < 0.001). MLR analysis indicated that log C-Fbg had a stronger relationship with log neutrophil counts than other certain inflammatory markers (p < 0.01). CONCLUSION: Serum C-Fbg levels increased in bacteremia patients, and this was consistent with an influx of neutrophils into the blood stream in accordance with the bacteremia phase.

The relationship between serum levels of LOX-1 ligand containing ApoAI as a novel marker of dysfunctional HDL and coronary artery calcification in middle-aged Japanese men.

BACKGROUND AND AIMS: Dysfunctional high-density lipoprotein (HDL) is a risk factor for cardiovascular disease (CVD) beyond HDL concentrations. Recently, a novel method has been introduced to measure LOX-1 ligand containing apolipoprotein AI (LAA), which is an indicator of various types of modified HDL with binding capacity to LOX-1 and related to impaired anti-atherogenic functions of HDL. This study aimed to examine the relationship between LAA as a novel marker of dysfunctional HDL and coronary artery calcification (CAC). METHODS: We selected 910 community-dwelling Japanese men aged 40-79 years without a history of CVD. The odds ratios per 1SD of LAA for the presence of CAC (Agatston score >10) were estimated using logistic regression model adjusted for confounders, including HDL-C or HDL particle (HDL-P) concentration. In addition, we performed further analysis stratified by age (<65 and ≥ 65 years). RESULTS: The mean age of the participants was 63.6 years, and the median LAA was 187.0 ng/mL. The prevalent CAC was 46.2%. The multivariable adjusted odds ratio (95% confidence interval) per 1SD of LAA for CAC was 1.14 (0.96-1.36) for all participants. After stratification by age, multivariable adjusted odds ratios per 1SD of LAA were 1.34 (1.02-1.76) and 0.97 (0.77-1.23) in men aged <65 and ≥ 65 years, respectively. CONCLUSIONS: The present study showed that LAA was associated with CAC independent of HDL-C or HDL-P in middle-aged Japanese men. This finding suggests that LAA might be an early marker for CVD events. Future longitudinal studies are warranted.

Highly oxidized low-density lipoprotein does not facilitate platelet aggregation.

OBJECTIVE: This study aimed to examine whether oxidized low-density lipoprotein (oxLDL) facilitates platelet aggregation, which is one cause for development of cardiovascular disease. METHODS: The susceptibility of platelets to aggregation was monitored by light transmittance aggregometry and a laser light scattering method using low-density lipoprotein (LDL) and oxLDL as agonists. ß-thromboglobulin (ß-TG) levels released from platelets were also measured after incubation with or without oxLDL. RESULTS: Platelet aggregation was suppressed by oxLDL as estimated by maximum light transmission. Additionally, adenosine diphosphate-induced further aggregation was slightly reduced by the presence of oxLDL. Aggregation levels of a low number of platelets, which was determined by the laser light scattering method, were lower upon addition of oxLDL compared with unoxidized LDL. After a short time of incubation, oxLDL increased secreted ß-TG levels in platelet-rich plasma. However, further incubation with oxLDL caused relatively lower secreted ß-TG levels compared with incubation with unoxidized LDL. This fluctuation was not due to ß-TG degradation by oxLDL. CONCLUSIONS: Levels of oxLDL in vitro weakly activate platelets at an early stage, but then inhibit platelet function, such as aggregation and ß-TG secretion.

Clinical impact of normal alanine aminotransferase on direct-acting antiviral outcome in patients with chronic hepatitis C virus infection.

BACKGROUND AND AIMS: This study aimed to clarify the clinical picture of hepatitis C virus (HCV) carriers with normal alanine aminotransferase (CNALT) and those with ALT elevation (non-CNALT) under direct-acting antivirals (DAAs). METHODS: We enrolled 1002 patients with HCV (427 men, median age: 69 years) who had received DAAs for comparisons between CNALT (ALT ≤33 U/L in males and ≤25 U/L in females; n = 374) and non-CNALT (n = 628) groups. RESULTS: CNALT patients displayed a higher platelet count (PLT) (170 000 vs 146 000/µL, P < 0.0001) and albumin (4.1 vs 4.1 g/dL, P = 0.0006) but lower AST (25 vs 51 U/L, P < 0.0001), alpha fetoprotein (3.2 vs 5.4 ng/mL, P < 0.0001), and liver fibrosis marker scores (all P < 0.0001). The sustained virologic response rate was comparable between the CNALT and non-CNALT groups (97.8 vs 95.3%, P = 0.106). The cumulative incidence of hepatocellular carcinoma (HCC) after DAA treatment was comparable between the CNALT and non-CNALT groups (P = 0.117, log-rank test). In CNALT patients with HCC history, PLT ≥150 000/µL was an independent risk factor of HCC recurrence (P = 0.019). In non-CNALT patients without HCC history, male gender (P = 0.021) and albumin <4.0 g/dL (P = 0.007) were independent risk factors, while PLT < 150 000/µL (P = 0.081) was a marginal risk factor of HCC occurrence. CONCLUSION: CNALT patients displayed a milder degree of liver fibrosis. Combinations of CNALT and PLT status might be useful as markers for HCC occurrence or recurrence surveillance.

Correlation of Pancreatic T1 Values Using Modified Look-Locker Inversion Recovery Sequence (MOLLI) with Pancreatic Exocrine and Endocrine Function.

Quantifying myocardial T1 values has been useful for detecting and characterizing fibrotic appearance in myocardial infarction, focal scars, and non-ischemic cardiomyopathies. Since pancreatic exocrine function decreases with chronic pancreatic fibrosis advancement, this study examined the correlation between pancreatic T1 values and pancreatic exocrine and endocrine insufficiency. METHODS: Thirty-two patients underwent abdominal contrast-enhanced MRI in our department between October 2017 and February 2019. We evaluated the T1 values of the pancreas using a modified Look-Locker inversion recovery sequence (MOLLI), pancreatic exocrine insufficiency (PEI) by fecal elastase 1 (FE1) values, and pancreatic endocrine insufficiency using fasting insulin and blood glucose levels to calculate the HOMA-ß. This trial is registered in the UMIN Clinical Trials Registry as UMIN 000030067. RESULTS: The median cohort (9 males and 23 females) age was 71 (range: 49-84) years. Eighteen patients had pancreatic cysts, three had alcohol-induced chronic pancreatitis, three had pancreatic cancer, and eight possessed other pancreatic features (two patients each with autoimmune pancreatitis, acute pancreatitis, or a bile duct tumor, one with idiopathic chronic pancreatitis, and one healthy control with negative findings). The median pancreatic T1 value measured by the MOLLI was 857.5 ms (597-2569). A significant negative correlation was found between the T1 mapping and FE1 values (r = 0.69, p < 0.01), with none for the T1 with HOMA-ß or serum albumin, triglycerides, or body mass index. CONCLUSIONS: the pancreatic T1 values correlated significantly with pancreatic exocrine function and might be useful in PEI diagnosis.

Cerebrospinal fluid biomarkers implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis.

OBJECTIVE: Hypertrophic pachymeningitis (HP) related to anti-neutrophil cytoplasmic antibody (ANCA) is the most frequently seen immune-mediated HP. We investigated cerebrospinal fluid (CSF) biomarkers related to the pathogenesis of ANCA-related HP (ANCA-HP). METHODS: The levels of B cell activation factor of the tumor necrosis factor family (BAFF), a proliferation-inducing ligand (APRIL), and transforming growth factor beta 1 (TGF-ß1) in the CSF were compared between patients with ANCA-HP (n = 12), other types of immune-mediated HP (other HP; n = 12), multiple sclerosis (MS; n = 14), and non-inflammatory neurological disorders (NIND; n = 10). In addition, we evaluated whether ANCA would be detected in CSF. RESULTS: CSF levels of BAFF, APRIL, and TGF-ß1 were significantly increased in ANCA-HP and other HP. In particular, BAFF and APRIL levels were significantly correlated with the IgG index in ANCA-HP. In other HP, BAFF and APRIL levels were significantly correlated with cell counts and protein levels in CSF. Of 12 patients with ANCA-HP, the CSF of 7 patients (58%) tested positive for myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA, while none of the CSF samples from other HP, MS, or NIND patients tested positive. CONCLUSION: The levels of BAFF, APRIL, and TGF-ß1 may serve as useful CSF biomarkers for assessing the disease activity of immune-mediated HP. Moreover, BAFF and APRIL in the CSF may be implicated in the pathogenesis of ANCA-HP via promoting autoreactive B cells, while detecting MPO- or PR3-ANCA in the CSF may be found in some patients with ANCA-HP.Key Points• CSF BAFF, APRIL, and TGF-ß1 levels increase significantly in immune-mediated HP.• CSF BAFF and APRIL levels are significantly correlated with IgG index in ANCA-HP.• Detection of MPO- or PR3-ANCA in the CSF is found in some patients with ANCA-HP.• BAFF, APRIL, and ANCA in the CSF may be implicated in the pathogenesis of ANCA-HP.

Clinical utility of FibroScan as a non-invasive diagnostic test for primary biliary cholangitis.

BACKGROUND AND AIM: Primary biliary cholangitis (PBC) is a chronic, slowly progressive, autoimmune liver disease. Some PBC patients display disease progression regardless of medical treatment. Therefore, it is important to accurately diagnose the clinical stage of PBC. This study investigated clinical merits of vibration-controlled transient elastography using FibroScan for assessing disease stage in PBC. METHODS: A total of 74 treatment-naïve PBC patients (84% female, median age: 64 years), 69 of whom having undergone histological assessment and five clinically diagnosed as at the cirrhosis stage, were enrolled for clinical comparisons of liver stiffness measurement (LSM) with other established indices. RESULTS: The number of patients with Nakanuma stages 1, 2, 3, and 4 was 18, 33, 17, and 6, respectively. The median LSM values for Nakanuma stages 1, 2, 3, and 4 were 5.05, 5.90, 8.90, and 23.70 kPa, respectively, and correlated significantly with disease progression based on Nakanuma's classification (r = 0.501, P < 0.001). LSM was also significantly related to other non-invasive serological markers (Mac-2 binding protein glycosylation isomer: r = 0.606, FIB-4 index: r = 0.493, and aspartate aminotransferase-to-platelet ratio index: r = 0.577; all P < 0.001). The areas under the receiver operating characteristic curve for diagnosing Nakanuma stage ≥ 2, stage ≥ 3, and stage 4 were 0.744, 0.763, and 0.907, respectively. A combination of LSM ≥ 7.0 kPa and Mac-2 binding protein glycosylation isomer ≥ 1.00 cut-off index could predict late-stage PBC (i.e. moderate to advanced disease progression) with a sensitivity of 0.58, specificity of 0.82, and accuracy of 0.74. CONCLUSIONS: Liver stiffness measurement using FibroScan provided simple, accurate, and non-invasive assessment of disease stage in PBC patients.