Search Results (19)

Background: The relationship between spleen and bone marrow stiffness, and other features of abnormal myeloproliferation has long been described. However, the scientific knowledge in this area remains very superficial. This review evaluated the diagnostic effectiveness of various ultrasound (US) methods in the assessment of neoplastic myeloproliferation using spleen stiffness measurement (SSM). Aim: To explore the diagnostic accuracy of US techniques in assessing spleen stiffness, determining which of them may be suitable for the diagnosis of myeloproliferative diseases in adults. Methods: The review included original retrospective or prospective studies published in the last five years (2019–2024) in peer-reviewed medical journals that reported receiver operating characteristics (ROCs) for SSM and the articles concerning the relation between SSM values and neoplastic myeloproliferation. The studies were identified through PubMed searches on 1 July and 1 December 2024. Quality was assessed using the QUADAS-2 tool. Results were tabulated according to the diagnostic method separately for myeloproliferative neoplasms (MNs) and for other clinical findings. Results: The review included 52 studies providing ROCs for SSM or compatibility between operators, and five studies covering the relation between SSM values and MNs. Conclusions: Acoustic radiation force impulse (ARFI), two-dimensional shear wave elastography (2D-SWE), transient elastography (TE), and point shear wave elastography (p-SWE) are promising methods for measuring SSM that can be incorporated into the diagnosis, screening, and monitoring system in MNs. Full article

Background and Aims: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease frequently associated with fatigue and mild cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays key roles in neuroplasticity, immune regulation, and metabolism. This study aimed to evaluate plasma BDNF levels in early-stage PBC and examine their clinical and biochemical associations. Methods: In this observational study, plasma BDNF, IL-6, and IL-18 concentrations were measured by ELISA in 45 patients with early-stage PBC and 31 age- and sex-matched healthy controls (mean age 60.5 years; 96% women). All participants underwent liver elastography using point shear wave elastography (ElastPQ), Doppler ultrasound, laboratory testing, and assessment of cognitive function (PHES) and fatigue severity (MFIS). Non-invasive fibrosis scores (APRI, FIB-4) were calculated. Results: Median plasma BDNF concentrations were significantly higher in PBC patients than in controls [median: 21.04 ng/mL (IQR: 10.68–38.07) vs. 5.80 ng/mL (IQR: 4.58–7.54); p < 0.0001]. In PBC patients, higher BDNF levels correlated inversely with liver stiffness measured by ElastPQ (R = −0.39, p = 0.0258), spleen dimensions, splenic vein flow volume (R = −0.49, p = 0.0018), suggesting an association with milder liver fibrosis and early hemodynamic alterations. A trend toward association between BDNF and IL-6 levels was observed in multivariate analysis. No significant associations were found between BDNF concentrations and markers of hepatocellular injury, cognitive performance, or fatigue severity. Conclusions: Plasma BDNF concentrations are elevated in early-stage PBC and inversely correlate with liver fibrosis severity. No significant associations were found with hepatocellular injury, cognitive function, or fatigue. These findings suggest that BDNF may play a protective role against hepatic fibrogenesis, or alternatively, that BDNF concentrations may decline with advancing liver disease. Further studies are needed to clarify its significance in PBC. Full article

Background/Objectives: Postmortem changes in tissue stiffness and organ morphology are critical for forensic medicine and pathology. Shear wave elastography (SWE) has emerged as a non-invasive tool to assess tissue stiffness, yet its potential for postmortem interval estimation remains underexplored. While previous studies have demonstrated early postmortem alterations in tissue elasticity, the temporal progression of these changes in different organs is not fully understood. This study aims to investigate the temporal changes in liver and spleen stiffness during the postmortem period using SWE and to evaluate the predictive potential of elastographic parameters for postmortem interval estimation. Methods: Twelve male Sprague–Dawley rats were sacrificed via cervical dislocation following deep anesthesia. Postmortem liver and spleen measurements, including longitudinal and short diameters and SWE values (kPa), were recorded at 0, 2, 4, 6, 9, 12, 18, 24, and 36 h. All elastographic measurements were obtained using a 5 mm circular region of interest (ROI) for the liver and a 3 mm ROI for the spleen. Changes over time were analyzed using repeated measures ANOVA, with post hoc Bonferroni corrections applied where necessary. Additionally, Receiver Operating Characteristic (ROC) curve analysis and binary logistic regression analysis were performed to assess the predictive accuracy of SWE parameters in estimating postmortem time. Results: Postmortem liver and spleen stiffness exhibited a significant declining trend over time (p < 0.001, η² = 0.749 and η² = 0.810, respectively). Liver and spleen dimensions initially increased, reaching peak values around 6 h, followed by a gradual reduction. ROC analysis demonstrated that spleen SWE (AUC = 0.917) and liver SWE (AUC = 0.845) were the strongest predictors of early postmortem time. Binary logistic regression further confirmed that liver and spleen SWE were statistically significant predictors of postmortem time (p = 0.006 and p = 0.020, respectively). Conclusions: This study provides evidence that postmortem liver and spleen stiffness decline progressively over time, while organ dimensions exhibit a biphasic pattern. Elastographic parameters, particularly SWE values, demonstrated strong predictive accuracy in estimating early postmortem intervals. These findings suggest that SWE may serve as a valuable imaging modality for forensic applications, providing objective insights into postmortem biomechanical changes and time-of-death estimation. Further research should explore the applicability of SWE in different tissue types and under varying environmental conditions. Full article

Background/Objectives: Esophageal varices (EVs) represent an important portal hypertension complication in patients with compensated advanced chronic liver disease (cACLD). Although upper gastrointestinal endoscopy is currently the gold standard for EV diagnosis, recent guidelines recommend non-invasive approaches to assess EV risk in cACLD patients to reduce unnecessary endoscopies. Our study aims to evaluate spleen stiffness measurement (SSM) using 2D shear-wave elastography (2D-SWE) as a non-invasive predictor of EV presence and severity in patients with cACLD. Methods: We included 73 cACLD patients referred to our liver clinic over one year. SSM and liver stiffness measurement (LSM) were performed using 2D-SWE, with specific cut-off values applied to rule in or rule out clinically significant portal hypertension (CSPH) according to Baveno VII consensus criteria. Upper gastrointestinal endoscopy was performed in all patients to confirm EV presence and grade. Results: Among all patients, 49.3% had no EV, while 50.7% presented with different EV grades (15.1% grade I, 13.7% grade II, 9.6% grade III, and 12.3% grade IV). A strong correlation was observed between elevated SSM values and EV presence, with SSM values > 32.8 kPa highly suggestive of EV (AUROC = 0.95, 95% CI: 0.909–0.995, p < 0.001). SSM values exceeding 40.4 kPa were associated with more advanced EV grades. Combining LSM and SSM improved diagnostic accuracy, effectively stratifying EV risk without invasive procedures. Conclusions: SSM via 2D-SWE is a promising, non-invasive tool for EV prediction in cACLD, aligning with Baveno VII recommendations to minimize unnecessary endoscopies. Further validation is required to refine diagnostic thresholds and expand applicability across different chronic liver disease etiologies. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer worldwide. More than 90% of cases occur in cirrhotic patients, with the degree of fibrosis being the main risk factor for the development of HCC. Liver biopsy is the gold-standard for fibrosis assessment, but it is an invasive procedure. Liver stiffness measurement (LSM) has shown high accuracy for diagnosing liver cirrhosis, as well as for predicting decompensation and HCC development. More recently, spleen stiffness measurement (SSM) has presented excellent results for ruling in/out high-risk varices and the presence of clinical significant portal hypertension. The aim of our study was to evaluate the relationship between LSM and SSM and the risk of hepatocellular carcinoma. Methods: A prospective study on cirrhotic patients was performed in a tertiary center from January 2020 to May 2024. All patients were submitted to liver and spleen elastography (with a new probe of 100 Hz) by the same blinded operator and were treated in the same institution for the development of hepatocellular carcinoma. Results: We included 299 cirrhotic patients, 75.9% male, with a mean age of 61.8 years (±10.0). The median value of LSM was 25.7 kPa [4.5–75.0] and that of SSM was 44.6 kPa [7.9–100.0]. The median follow-up time was 505 days [114.0–1541.0]. During this period, 18 patients developed HCC, with a median time to HCC diagnosis after LSM and SSM of 321 days [63.0–1227.0]. LSM was the only factor associated with the development of HCC (p = 0.002) with an AUC of 0.715. On the other hand, SSM was not associated with the development of HCC. Conclusions: We found that the risk of developing HCC is associated with liver fibrosis but not with portal hypertension (assessed using SSM). Full article

Vascular liver diseases (VLDs) include different pathological conditions that affect the liver vasculature at the level of the portal venous system, hepatic artery, or venous outflow system. Although serological investigations and sometimes histology might be required to clarify the underlying diagnosis, imaging has a crucial role in highlighting liver inflow or outflow obstructions and their potential causes. Cross-sectional imaging provides a panoramic view of liver vascular anatomy and parenchymal patterns of enhancement, making it extremely useful for the diagnosis and follow-up of VLDs. Nevertheless, multiparametric ultrasound analysis provides information useful for differentiating acute from chronic portal vein thrombosis, distinguishing neoplastic invasion of the portal vein from bland thrombus, and clarifying the causes of venous outflow obstruction. Color Doppler analysis measures blood flow velocity and direction, which are very important in the assessment of VLDs. Finally, liver and spleen elastography complete the assessment by providing intrahepatic and intrasplenic stiffness measurements, offering further diagnostic information. Full article

Background: Thrombotic adverse events and disease progression are crucial in Polycythemia Vera (PV), as it stands as the leading cause of mortality. The pulse wave velocity (PWV) is a valuable indicator of arterial aging and often plays a significant independent role in contributing to cardiovascular adverse events (CV-AEs). The aim of this study was to examine the relationship between PWV and critical vascular function parameters, with the goal of identifying new predictive factors of vascular damage and exploring a potential connection with disease progression. Methods: Non-invasive aortic stiffness was assessed through carotid–femoral PWV measurement. PWV was measured using the SphygmoCor device. History of arterial or venous thrombosis (TAEs) or other CV-AEs was collected at baseline. PWV measurements were repeated at baseline, at 6 and at 12 months. Results: The study involved 28 PV patients aged 27 to 77 years, with 57.1% being male. Fourteen patients (50%) reported a high-risk thrombotic score at diagnosis, and 60.7% had at least one comorbidity. Multivariable regression models showed that hemoglobin levels were independently associated with PWV (β: 0.68, SE 0.24, p < 0.01). During the follow-up period (median duration 21.3 months, range 6–33), a total of 13 events were documented. Specifically, two patients exhibited a loss of response to treatment, four patients presented an increase in spleen diameters, three patients displayed an escalation of systemic symptoms, and three patients had a clear progression to secondary myelofibrosis. PWV (per 1 m/s: OR 1.70, 95% CI 1.00–2.91, p = 0.047) and leukocyte count (per 1 × 10³/μL: OR 1.47, 95% CI: 1.04–2.09, p = 0.043) were significant predictors of events, independently of waist circumference, blood pressure, treatment, and hematocrit. Conclusions: PWV has demonstrated its potential as an effective tool for monitoring PV patients. It stands as a clinical parameter that can predict the risk of progression in PV patients. Further investigation is essential to fully explore this potential. If successful, it could offer clinicians a valuable resource for effectively managing PV patients. Full article

Clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease indicates an increased risk of decompensation and death. While invasive methods like hepatic venous–portal gradient measurement is considered the gold standard, non-invasive tests (NITs) have emerged as valuable tools for diagnosing and monitoring CSPH. This review comprehensively explores non-invasive diagnostic modalities for portal hypertension, focusing on NITs in the setting of hepatitis B and hepatitis C virus-related cirrhosis. Biochemical-based NITs can be represented by single serum biomarkers (e.g., platelet count) or by composite scores that combine different serum biomarkers with each other or with demographic characteristics (e.g., FIB-4). On the other hand, liver stiffness measurement and spleen stiffness measurement can be assessed using a variety of elastography techniques, and they can be used alone, in combination with, or as a second step after biochemical-based NITs. The incorporation of liver and spleen stiffness measurements, alone or combined with platelet count, into established and validated criteria, such as Baveno VI or Baveno VII criteria, provides useful tools for the prediction of CSPH and for ruling out high-risk varices, potentially avoiding invasive tests like upper endoscopy. Moreover, they have also been shown to be able to predict liver-related events (e.g., the occurrence of hepatic decompensation). When transient elastography is not available or not feasible, biochemical-based NITs (e.g., RESIST criteria, that are based on the combination of platelet count and albumin levels) are valid alternatives for predicting high-risk varices both in patients with untreated viral aetiology and after sustained virological response. Ongoing research should explore novel biomarkers and novel elastography techniques, but current evidence supports the utility of routine blood tests, LSM, and SSM as effective surrogates in diagnosing and staging portal hypertension and predicting patient outcomes. Full article

Spleen stiffness measurement (SSM) by transient elastography (TE) has been repeatedly demonstrated as the reliable way to rule out the presence of high-risk esophageal varices (HRV). We aimed to evaluate and compare novel vs. standard TE-SSM module performance in diagnosing HRV in patients with compensated advanced chronic liver disease (cACLD). This retrospective study included patients with cACLD; blood data, upper digestive endoscopy performed within 3 months of TE, SSM@50Hz and SSM@100Hz were collected. Overall, 112 patients with cACLD were analyzed (75.9% males, average age of 66, 43.7% alcohol-related chronic liver disease, 22.3% metabolic-associated steatotic liver disease, 6.2% viral hepatitis). Reliable SSM was possible in 80.3% and 93.8% of patients by using SSM@50Hz and SSM@100Hz probe, respectively. At the cut-off 41.8 kPa and 40.9 kPa (Youden), SSM@50Hz and SSM@100Hz had AUROCs of 0.746 and 0.752, respectively, for diagnosing HRV (p = 0.71). At the respective cut-offs, sensitivities for HRV were 92.9% and 100%, resulting in misclassification rates of 7.1% and 0% by using SSM@50Hz and SSM@100Hz. SSM reliably excludes HRV in cACLD patients, with measurements below 41 kPa potentially avoiding EGD in around 50% of cases, with minimal risk of HRV omission. SSM@100Hz demonstrated less measurement failures and no HRV misclassification. Full article

Acoustic radiation forced impulse (ARFI) is an integrated ultrasound method, measuring stiffness by point shear wave elastography. To evaluate the diagnostic performance of the ARFI of the liver and the spleen, combined with spleen dimension and platelet count, in predicting high-risk esophageal varices (HRVs) in cirrhotic patients, a prospective and cross-sectional study was conducted between February 2017 and February 2021. The following ratio scores were calculated based on ARFI measurements: ALSDP (ARFI Liver–Spleen Diameter-to-Platelet Ratio Score), ASSDP (ARFI Spleen–Spleen Diameter-to-Platelet Ratio Score), ASSAP (ARFI Spleen–Spleen Area-to-Platelet Ratio Score), and ALSAP (ARFI Liver–Spleen Area-to-Platelet Ratio Score). In 100 enrolled subjects, spleen ARFI, ASSDP, and ASSAP were significantly associated with HRVs in the prospective short- and long-term follow-ups and in the cross-sectional study (p < 0.05), while ALSDP and ALSAP were associated with HRVs only in the prospective long-term follow-up and cross-sectional study (p< 0.05). ASSAP was the best ARFI ratio score for HRVs at the long-term follow-up [value of area under curve (AUC) = 0.88], although all the ARFI ratio scores performed better than individual liver and spleen ARFI (AUC > 0.7). In our study, ARFI ratio scores can predict, in well-compensated cirrhotic patients, the risk of developing HVRs in short- and long-term periods. Full article

Background and Aims: The presence of portal hypertension in cirrhotic patients is a major prognostic factor associated with the development of severe complications and increased mortality. The gold standard for diagnosing portal hypertension is the hepatic venous pressure gradient. More recently, spleen stiffness has emerged as a new and non-invasive diagnostic tool, and has already been included in the last Baveno VII guidelines. The exact prevalence of Helicobacter pylori infection, pre-malignant lesions and their relation to portal hypertension have never been described. The aim of our study was to evaluate the relationship between the presence of portal hypertension assessed via liver and spleen elastography and Helicobacter pylori infection and pre-malignant gastric lesions. Methods: An observational study was conducted, including consecutive patients admitted from December 2020 to December 2022. All patients underwent upper endoscopy and were also subjected to liver and spleen elastography (using the new probe of 100 Hz) by the same blinded operator in a tertiary center. Results: We included 155 cirrhotic patients, with a mean age of 64.1 years (±8.8), and 81.3% were male. The most common etiology was alcoholic liver disease (72.9%). The median value of liver stiffness measurement was 24.4 kPa [3.1–75.0], and the spleen stiffness measurement was 49.1 kPa [12.8–100.0]. Akin to endoscopic findings, 50.3% presented esophageal varices, 5.2% gastric atrophy, 11.6% gastric metaplasia, and 32.9% portal hypertension gastropathy. Regarding histologic findings, we found that 34.8% presented H. pylori infection, 35.5% gastric atrophy (OLGA 1—58.2%) and 38.7% gastric metaplasia (OLGIM 1—63.3%). Liver stiffness and spleen stiffness measurements were associated with the presence of portal hypertensive gastropathy (p < 0.01), but not with H. pylori infection or pre-malignant gastric lesions. Conclusions: Although present in almost one third of cirrhotic patients, H. pylori infection and pre-malignant gastric lesions are not associated with liver stiffness and spleen stiffness measurements. On the other hand, we found an association between liver stiffness and spleen stiffness measurements and portal hypertensive gastropathy. Full article

Currently, most primary hospitals cannot routinely perform liver stiffness measurements (LSMs) and spleen stiffness measurements (SSMs), which are recommended by guidelines to exclude high-risk varices (HRVs). We tried to find more convenient indicators for HRV screening. We enrolled 213 cirrhosis patients as the training cohort (TC) and 65 primary biliary cirrhosis patients as the validation cohort (VC). We included indicators such as SSM by two-dimensional shear wave elastography, LSM by transient elastography, and other imaging and laboratory tests. Variable analysis revealed SSM, platelets (PLT), and spleen thickness (ST) as independent risk indicators for HRV. In TC, ST+PLT (ST < 42.2 mm and PLT > 113.5 × 10⁹/L) could avoid 35.7% of the esophagogastroduodenoscopies (EGDs), with a 2.4% missed HRV rate. Although the proportion of EGDs spared by ST+PLT was less than SSM+PLT (SSM < 29.89 kPa + PLT > 113.5 × 10⁹/L) (35.7% vs. 44.1%), it was higher than that of the Baveno VI criteria (B6) (35.7% vs. 28.2%). We did not validate SSM+PLT in VC considering our aims. ST+PLT safely spared 24.6% of EGDs in VC, identical to B6. Conclusions: The ability of ST+PLT to exclude HRVs was superior to B6 but slightly inferior to SSM+PLT. When SSM cannot be routinely performed, ST+PLT provides an extra option for patients to exclude HRVs as a more convenient model. Full article

Purpose: Magnetic resonance elastography (MRE) has been established as the most accurate noninvasive technique for diagnosing liver fibrosis. Recent publications have suggested that the measurement of splenic stiffness is useful in setting where portal hypertension may be present. The goal of the current study was to compile normative data for MRE-assessed stiffness measurements of the spleen in young adults. Materials and Methods: A total of 100 healthy young Caucasian volunteers (65 females and 35 males) in the age range of 20 to 32 years were enrolled in this study. The participants reported no history of chronic spleen and liver disease, normal alcohol consumption, and a normal diet. The MRE data were acquired by using a 1.5 T whole-body scanner and a 2D GRE pulse sequence with 60 Hz excitation. Spleen stiffness was calculated as a weighted mean of stiffness values in the regions of interest manually drawn by the radiologist on three to five spleen slices. Results: Mean spleen stiffness was 5.09 ± 0.65 kPa for the whole group. Male volunteers had slightly higher splenic stiffness compared to females: 5.28 ± 0.78 vs. 4.98 ± 0.51 kPa, however, this difference was not statistically significant (p = 0.12). Spleen stiffness did not correlate with spleen fat content and liver stiffness but a statistically significant correlation with spleen volume was found. Conclusions: The findings of this study provide normative values for 2D MRE-based measurement of spleen stiffness in young adults, a basis for assessing the value of this biomarker in young patients with portal system pathologies. Full article

Tissue engineering has emerged as an indispensable tool for the reconstruction of organ-specific environments. Organ-derived extracellular matrices (ECM) and, especially, decellularized tissues (DCL) are recognized as the most successful biomaterials in regenerative medicine, as DCL preserves the most essential organ-specific ECM properties such as composition alongside biomechanics characterized by stiffness and porosity. Expansion of the DCL technology to cancer biology research, drug development, and nanomedicine is pending refinement of the existing DCL protocols whose reproducibility remains sub-optimal varying from organ to organ. We introduce a facile decellularization protocol universally applicable to murine organs, including liver, lungs, spleen, kidneys, and ovaries, with demonstrated robustness, reproducibility, high purification from cell debris, and architecture preservation, as confirmed by the histological and SEM analysis. The biomechanical properties of as-produced DCL organs expressed in terms of the local and total stiffness were measured using our facile methodology and were found well preserved in comparison with the intact organs. To demonstrate the utility of the developed DCL model to cancer research, we engineered three-dimensional tissue constructs by recellularization representative decellularized organs and collagenous hydrogel with human breast cancer cells of pronounced mesenchymal (MDA-MB-231) or epithelial (SKBR-3) phenotypes. The biomechanical properties of the DCL organs were found pivotal to determining the cancer cell fate and progression. Our histological and scanning electron microscopy (SEM) study revealed that the larger the ECM mean pore size and the smaller the total stiffness (as in lung and ovary), the more proliferative and invasive the mesenchymal cells became. At the same time, the low local stiffness ECMs (ranged 2.8–3.6 kPa) did support the epithelial-like SKBR-3 cells’ viability (as in lung and spleen), while stiff ECMs did not. The total and local stiffness of the collagenous hydrogel was measured too low to sustain the proliferative potential of both cell lines. The observed cell proliferation patterns were easily interpretable in terms of the ECM biomechanical properties, such as binding sites, embedment facilities, and migration space. As such, our three-dimensional tissue engineering model is scalable and adaptable for pharmacological testing and cancer biology research of metastatic and primary tumors, including early metastatic colonization in native organ-specific ECM. Full article

Portal hypertension is a common manifestation in late-to-end-stage liver diseases and can cause severe complications such as ascites, hepatic encephalopathy, etc. However, an early diagnosis of portal hypertension is often difficult as it can be asymptomatic. Though the gold standard to diagnose portal hypertension is hepatic vein catheterization, ultrasound elastography is regarded as a noninvasive alternative that can be used to accurately predict portal hypertension and a few further complications such as gastro-esophageal varices. Since ultrasound elastography is available in most medical centers, and is cheaper and noninvasive, studying its function in predicting portal hypertension is of paramount importance. Therefore, this review generalized the results of recently published articles in order to establish the indicators that were related to diagnostic and prediction efficiency. Our study found that various technologies of ultrasound elastography could be used to predict portal hypertension with satisfactory diagnostic sensitivity, specificity, accuracy, and AUC. Meanwhile, we also recognized similar diagnostic efficiency of ultrasound elastography in gastro-esophageal varices. Full article