[Application Values of New Ultrasound Technologies in the Diagnosis of Hepatic Sinusoidal Obstruction Syndrome].

Hepatic sinusoidal obstruction syndrome (HSOS),a toxic liver injury,can lead to multiple organ failure in severe cases and is even fatal.Early diagnosis is of great significance for the selection of treatment regimens and prognosis.Currently,ultrasound,as the preferred diagnostic method for liver diseases,has been recommended in expert consensus and criteria for the diagnosis of HSOS.However,there are no definitive imaging diagnostic standards.This paper summarizes the sonographic features of ultrasound and new ultrasound technologies in HSOS research.Analyzing the characteristic sonographic images from gray-scale ultrasonography,Doppler ultrasonography,ultrasound elastography,and contrast-enhanced ultrasonography at different stages of the disease enables the establishment and refining of the corresponding imaging diagnostic standards and provides effective auxiliary examination methods for the early diagnosis and differential diagnosis of HSOS.

Hepatic Sinusoidal Disorders.

Hepatic sinusoids are highly specialized microcirculatory conduits within the hepatic lobules that facilitate liver functions. The sinusoids can be affected by various disorders, including sinusoidal dilatation, sinusoidal obstruction syndrome (SOS), sinusoidal cellular infiltration, perisinusoidal infiltration, and endothelial neoplasms, such as hemangioendothelioma and angiosarcoma. While these disorders, particularly SOS and neoplasms, can be life threatening, their clinical manifestation is often nonspecific. Patients may present with right upper quadrant pain, jaundice, hepatomegaly, ascites, splenomegaly, and unexplained weight gain, although the exact manifestation depends on the cause, severity, and duration of the disease. Ultimately, invasive tests may be necessary to establish the diagnosis. A comprehensive understanding of imaging manifestations of various sinusoidal disorders contributes to early diagnosis and can help radiologists detect subclinical disease. Additionally, specific imaging features may assist in identifying the cause of the disorder, leading to a more focused and quicker workup. For example, a mosaic pattern of enhancement of the liver parenchyma is suggestive of sinusoidal dilatation; peripheral and patchy reticular hypointensity of the liver parenchyma on hepatobiliary MR images is characteristic of SOS; and associated diffuse multiple hyperintensities on diffusion-weighted images may be specific for malignant sinusoidal cellular infiltration. The authors provide an overview of the pathogenesis, clinical features, and imaging appearances of various hepatic sinusoidal disorders, with a special emphasis on SOS. ©RSNA, 2024 Supplemental material is available for this article.

Review of imaging findings in hepatic veno-occlusive disease.

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation. Patients present with right upper-quadrant abdominal pain, jaundice, weight gain, and conjugated hyperbilirubinemia. Early diagnosis of VOD is essential to promptly initiate defibrotide therapy, which has been demonstrated to enhance survival and achieve complete resolution of disease in some patients. Historically, VOD was diagnosed by the modified Seattle or Baltimore criteria, which are both based on clinical symptoms. Alongside advancements in medical imaging over the last 40 years, the diagnosis of VOD has evolved to include the use of ultrasound, elastography, cross-sectional imaging, and image guided biopsy. Identification and interpretation of findings of VOD across imaging modalities is now a critical aspect of post-HSCT care. This review will outline the imaging findings and recommendations for the use of imaging in the management of VOD including gray-scale, color and spectral Doppler ultrasound, ultrasound elastography, CT, MRI, and liver biopsy.

Shear wave elastography and dispersion imaging for hepatic veno-occlusive disease prediction after pediatric hematopoietic stem cell transplantation: a feasibility study.

BACKGROUND: Non-invasive imaging modalities are warranted for diagnosing and monitoring veno-occlusive disease because early diagnosis and treatment improve the prognosis. OBJECTIVE: To evaluate the usefulness of liver shear wave elastography (SWE) and shear wave dispersion (SWD) imaging in diagnosing and monitoring veno-occlusive disease in pediatric patients. MATERIALS AND METHODS: We conducted a prospective cohort study at a single tertiary hospital from March 2021 to April 2022. The study protocol included four ultrasound (US) sessions: a baseline US and three follow-up US after hematopoietic stem cell transplantation. Clinical criteria, including the European Society for Blood and Marrow Transplantation criteria, were used to diagnose veno-occlusive disease. We compared clinical factors and US parameters between the veno-occlusive disease and non-veno-occlusive disease groups. The diagnostic performance of US parameters for veno-occlusive disease was assessed by plotting receiver operating characteristic (ROC) curves. We describe temporal changes in US parameters before and after veno-occlusive disease diagnosis. RESULTS: Among the 38 participants (mean age 10.7 years), eight developed veno-occlusive disease occurring 17.0 ± 5.2 days after hematopoietic stem cell transplantation. Liver stiffness, as measured by SWE (15.0 ± 6.2 kPa vs. 5.8 ± 1.8 kPa; P<0.001), and viscosity, as assessed with SWD (17.7 ± 3.1 m/s/kHz vs. 14.3 ± 2.8 m/s/kHz; P=0.015), were significantly higher in the veno-occlusive disease group compared to the non-veno-occlusive disease group at the time of diagnosis. Liver stiffness demonstrated the highest area under the ROC (AUROC) curves at 0.960, with an optimal predictive value of >6.5 kPa, resulting in sensitivity and specificity of 100% and 83.3%, respectively. Viscosity demonstrated an AUROC of 0.783, with an optimal cutoff value of 13.9 m/s/kHz for predicting veno-occlusive disease, with a sensitivity of 100% and specificity of 53.3%, respectively. Liver stiffness increased with disease severity and decreased during post-treatment follow-up. CONCLUSION: SWE may be a promising technique for early diagnosis and severity prediction of veno-occlusive disease. Furthermore, liver viscosity assessed by SWD may serve as an additional marker of veno-occlusive disease.

Utility of liver stiffness measurement in the diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease after hematopoietic stem cell transplantation.

PURPOSE: We aimed to assess the role of liver stiffness measurement (LSM), evaluated using transient elastography (TE), for the diagnosis of sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD), a complication of hematopoietic stem cell transplantation (HSCT). METHODS: In this retrospective study, ultrasonography (US) and LSM were performed on 86 adult patients (55 men and 31 women) undergoing HSCT between January 2016 and December 2022. Characteristics and changes in liver stiffness (LS) were compared between patients with and without SOS/VOD. RESULTS: Of the 86 patients, 14 were diagnosed with SOS/VOD. A significant increase in LS (ranging from 12.6 to 55.1 kPa, median 23.8 kPa) compared to pre-HSCT values was observed in all patients who developed SOS/VOD. The area under the receiver operating characteristic curve (AUROC) for the diagnosis of SOS/VOD was 0.9663 (0.933-0.995) for LS ≥ 17.4 kPa after HSCT. Post-transplant LS exceeded 17.4 kPa in all 14 patients in the SOS/VOD group (100%) and in seven patients in the non-SOS/VOD group (9.7%). The sensitivity and specificity were 100% and 90.3%, respectively. AUROC for the diagnosis of SOS/VOD was 0.973 (0.943-1.000) for LS increase ≥ + 12.6 kPa from baseline after HSCT. The change of ≥ + 12.6 kPa from baseline was observed in all 14 patients in the SOS/VOD group (100%) and in four patients in the non-SOS/VOD group (5.6%). The sensitivity and specificity were 100% and 94.4%, respectively. CONCLUSION: LSM using TE may contribute to establishing the diagnosis of SOS/VOD after HSCT.

Prospective Assessment of Treatment-Induced Liver Injury as a Cause of Diffuse Pathologic Hepatic Enhancement in Contrast-Enhanced Ultrasound.

OBJECTIVE: A hypo-enhancement of the liver in contrast-enhanced ultrasound (CEUS), pathologic one-minute hepatic enhancement (pOMHE), was recently observed in 70% of allogeneic hematopoietic stem cell transplantation patients with a high-risk profile for veno-occlusive disease (VOD). Whether pOMHE was a pre-clinical sign of VOD or an unspecific feature of liver damage secondary to intensive chemotherapy is unclear. METHODS: To investigate this, we studied CEUS patterns in patients receiving high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation (auto-HSCT) or intensive induction therapy (IT) for the treatment of acute leukemia. From April 2020 to May 2021, patients undergoing auto-HSCT (n = 20) or acute leukemia patients prior to IT (n = 20) were included. All patients underwent a B-mode ultrasound and CEUS of the liver and spleen before treatment (d0) and on day 10 (d10) after therapy start. The one-minute hepatic enhancement was quantified. An optical density of liver enhancement less than 90% compared with the spleen was considered pathologic (pOMHE). Clinical and laboratory parameters used to assess a drug-induced liver injury (DILI) were documented. RESULTS: The OMHE was normal (d0 and d10) in 36 (90%) patients. After IT, 2 of 20 patients had a pOMHE. A DILI grade IV was diagnosed in one case and hyperfibrinolysis in the second case. In 2 of 20 (5%) auto-HSCT patients a pOMHE was observed at d10 without clinical symptoms. CONCLUSION: Chemotherapy-induced effects are not the cause of a pathologic liver enhancement. In contrast, severe DILI or hyperfibrinolysis can be associated with pOMHE.

HokUS-10 scoring system predicts the treatment outcome for sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation.

Hepatic sinusoidal obstruction syndrome (SOS) is a severe and life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a multi-center retrospective study to evaluate the utility of our ultrasonographic scoring system for the diagnosis of SOS (HokUS-10) in predicting SOS-related mortality (SOS-RM). We analyzed a total of 42 patients who developed SOS after HSCT. The cumulative incidences of SOS-RM, non-relapse mortality (NRM), and overall survival at day 180 after the diagnosis of SOS were 26.4%, 28.8% and 54.5%, respectively. The area under the receiver operating characteristic curve analysis showed that the optimal cut-off value of HokUS-10 total score to predict SOS-RM was 8 points after the treatment of SOS. In the individual HokUS-10 score, ascites and portal vein flow-related scores (PV mean velocity and PV flow direction) after the treatment of SOS were shown as significant risk factors for SOS-RM. Our study suggested that US findings after the treatment can predict the treatment outcomes for SOS.

Assessment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome using different scanning approaches for the ultrasonographic evaluation of portal vein blood flow and hepatic artery resistive index in hematopoietic stem cell transplant recipients.

PURPOSE: Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Previously, we established a scoring system (Hokkaido ultrasound-based scoring system-10; HokUS-10) comprising 10 ultrasound parameters for SOS diagnosis. In HokUS-10, the portal vein time-averaged flow velocity (PV TAV) and hepatic artery resistive index (HA RI) are measured using subcostal scanning. However, measurement errors and delineation difficulties occur. Therefore, we aimed to prospectively evaluate PV TAV and HA RI measurements obtained via intercostal scanning as an alternative method to subcostal scanning and determine their cutoff values. METHODS: HokUS-10 was administered before and after HSCT. PV TAV and HA RI were measured on subcostal and right intercostal scans. RESULTS: We performed 366 scans on 74 patients. The median value (range) of PV TAV in the main and right portal veins was 15.0 cm/s (2.2-49.6 cm/s) and 10.5 cm/s (1.6-22.0 cm/s), respectively. A low correlation was observed between the two values (r = 0.39, p < 0.01). The highest diagnostic value of the right portal vein was less than 8.0 cm/s. The median value (range) of HA RI in the proper and right hepatic arteries was 0.72 (0.52-1.00) and 0.70 (0.51-1.00), respectively. A strong correlation was observed between the two values (r = 0.65, p < 0.01). The highest diagnostic value of the right HA RI was 0.72 or higher. CONCLUSION: Quantitative measurement of PV TAV and HA RI using intercostal scanning can be appropriately performed as an alternative method to using subcostal scanning.

Point shear-wave elastography for the diagnosis of veno-occlusive disease in children and young adults.

BACKGROUND: Hepatic veno-occlusive disease or sinusoidal obstruction syndrome is a potentially life-threatening complication of hematopoietic stem cell transplantation. OBJECTIVE: To assess the usefulness of point shear-wave elastography (pSWE) for the early diagnosis of sinusoidal obstruction syndrome (SOS) in children. MATERIALS AND METHODS: A retrospective study was carried out in 43 patients with suspected SOS assessed between March 2018 and November 2021. Diagnosis of SOS was confirmed in 28 patients based on the European Society for Blood and Marrow Transplantation diagnostic criteria. Abdominal ultrasound and pSWE of the liver were performed before and after hematopoietic stem cell transplantation on first suspicion of SOS. RESULTS: Liver stiffness on initial suspicion was higher in patients diagnosed with SOS and these values increased compared to the pre-transplantation values. A cutoff value of 1.37 m/s was found for the diagnosis of SOS, with an area under the curve of 0.779 (95% CI 0.61-0.93). CONCLUSION: Point shear wave elastography of the liver is a promising technique for the early diagnosis of pediatric SOS.

Usefulness of ultrasonography and elastography in diagnosing oxaliplatin-induced sinusoidal obstruction syndrome.

BACKGROUND: Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early. METHODS: In this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT. RESULTS: Of the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32-0.41). The change in rate of LSM by SWE was correlated with an SV increase ≥ 30% (r = 0.40). CONCLUSIONS: The usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS.

Imaging features of hepatic sinusoidal obstruction syndrome or veno-occlusive disease in children.

Hepatic sinusoidal obstruction syndrome, also known as veno-occlusive disease, can occur as a complication of myeloablative chemotherapy, as a result of low-intensity chemotherapy-related liver toxicity or radiotherapy of the liver. Symptoms of sinusoidal obstruction syndrome can range from asymptomatic to liver dysfunction or severe disease with life-threatening acute multi-organ failure. Imaging features can suggest or support this clinical diagnosis. Familiarity with the imaging spectrum of sinusoidal obstruction syndrome is therefore important for both radiologists and clinical oncologists. Here, multi-modality radiologic appearances of sinusoidal obstruction syndrome in pediatric patients are illustrated, including outcome after follow-up.

Grayscale and Spectral Doppler Ultrasound in the Diagnosis of Hepatic Veno-occlusive Disease/Sinusoidal Obstruction Syndrome After Hematopoietic Stem Cell Transplantation in Children.

The aim of this study is to determine the ultrasound criteria in the diagnosis of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after hematopoietic stem cell transplantation (HSCT) in children. A total of 158 pediatric patients underwent HSCT between January 2016 and January 2018. In all, 71 patients with clinically suspicious hepatic VOD/SOS have been followed with serial ultrasound examinations. Hepatomegaly, gallbladder wall thickening, ascites, pleural effusion, reverse flow in the portal vein, and diameter and peak systolic velocity of the hepatic artery were evaluated. Patients were divided into 2 groups retrospectively: VOD/SOS and non-VOD/SOS. The predictive value of all findings was determined, respectively. Gallbladder wall thickening, increase of diameter and peak systolic velocity of the hepatic artery, and the presence of ascites are highly predictive for VOD/SOS (P=0.001 and < 0.05). The reversed portal venous flow was developed in 3 patients in the VOD/SOS group, no significant difference was found between the 2 groups (P>0.05). Hepatomegaly was recorded in 29 (70.7%) patients in the VOD/SOS group, 13 of them was presented related to a primary disease. Pleural effusion is not associated with the diagnosis of VOD/SOS (P>0.05). Gallbladder wall edema, an increase of peak systolic velocity of the hepatic artery, and the presence of ascites are highly related to the diagnosis of VOD/SOS in children after HSCT. Ultrasound findings must be correlated with clinical criteria.

Refined ultrasonographic criteria for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.

Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS.

Quantitative CT assessment by histogram and volume ratio in pyrrolizidines alkaloids-induced hepatic sinusoidal obstruction syndrome.

OBJECTIVE: To quantitatively assess hypoattenuation volume ratio and hepatic parenchymal hypoattenuation on contrast enhanced computed tomography (CECT) in patients with pyrrolizidines alkaloids (PAs)-induced hepatic sinusoidal obstruction syndrome (HSOS), and evaluate the correlations of the CT-based quantitative values with clinical factors. METHODS: Thirty-five patients with PAs-induced HSOS who underwent CECT were retrospectively enrolled. The ratio of hypoattenuation volume to total liver volume, and changes in damaged area-to-normal liver density ratio (ΔDR) derived from histogram on portal venous phase were quantitatively measured. Heterogeneous hypoattenuation (CT score) scored by hypoattenuation volume ratio and ΔDR were calculated. The correlation between imaging findings and clinical factors was analyzed using Pearson correlation test. RESULTS: Liver function tests were abnormal in most patients, the mean Hounsfield unit (HU) of damaged area (58.68 ± 17.3) was significantly lower (P < 0.001) than the corresponding normal liver (82.27 ± 23.97). Heterogeneous hypoattenuation were mild in 13 patients (37 %), moderate in 16 patients (46 %), and severe in 6 patients (17 %). ΔDR derived from histogram was positively correlated (weakly to moderately) with total bilirubin (r = 0.341, P = 0.045), direct bilirubin (r = 0.385, P = 0.022), and alkaline phosphatase (r = 0.491, P = 0.003), while such correlation was not observed in hypoattenuation volume ratio. The severity of heterogeneous hypoattenuation scored by hypoattenuation volume ratio and ΔDR was positively correlated (weakly) with prothrombin time (r = 0.357, P = 0.035), international normalized ratio (r = 0.363, P = 0.032), alkaline phosphatase (r = 0.359, P = 0.034), and model for end-stage liver disease (MELD) score (r = 0.347, P = 0.041). CONCLUSION: Heterogeneous hypoattenuation scored by volume ratio and ΔDR on CECT provides a non-invasive approach in evaluating the severity of PAs-induced HSOS.

Reliability of an ultrasonographical scoring system for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease in patients with hematopoietic stem cell transplantation.

PURPOSE: Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a fatal complication after hematopoietic stem cell transplantation. We previously reported the usefulness of an ultrasonographical (US) scoring system, the Hokkaido US-based scoring system consisting of ten parameters (HokUS-10): (1) hepatomegaly in the left lobe and (2) right lobe, (3) dilatation of the main portal vein (PV), (4) hepatofugal flow in the main PV, (5) decreased velocity of the PV, (6) dilatation of the para-umbilical vein (PUV), (7) appearance of blood flow signal in the PUV, (8) gallbladder (GB) wall thickening, (9) ascites, and (10) increased resistive index of the hepatic artery, for the diagnosis of SOS/VOD. However, the reliability of this system among operators remains elusive. Therefore, we prospectively evaluated the reliability of HokUS-10. METHODS: Twenty-four healthy volunteers and 40 patients with liver dysfunction were enrolled. Inter- and intra-operator reliabilities were analyzed using three sonographers. RESULTS: The median concordance rate of HokUS-10 among three sonographers and intra-operator in 24 volunteers was 92% (95% CI: 73-98%) and 98% (95% CI: 92-100%), respectively. In all 64 cases, in terms of the reliability between two sonographers for three representative US parameters (amount of ascites, GB wall thickening, and appearance of PUV blood flow signal), the median concordance rate was more than 98% (95% CI: 86-106%). CONCLUSION: The inter- and intra-reliabilities of HokUS-10 were excellent. Thus, US might be a reliable tool for SOS/VOD diagnosis.

Elastography improves accuracy of early hepato-biliary complications diagnosis after allogeneic stem cell transplantation.

Significant morbidity and mortality have been associated with liver complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Causes and consequences of these hepato-biliary complications are various and might be life-threatening. A high misdiagnosis rate has been reported because of a weak correlation between clinical, laboratory and imaging data. Liver elastography, a liver stiffness measure, is able to assess liver fibrosis and portal hypertension in most liver diseases, but data after allo-HSCT are scarce. Our aim was to determine the interest of sequential liver stiffness measurements for the diagnosis of early hepatic complications after allo-HSCT. Over a two years period of time, 161 consecutive adult patients were included and 146 were analyzed. Ultrasonography and elastography measurements were performed before transplantation, at day+7 and day+14 by three different experienced radiologists unaware of patients'clinical status. Eighty-one (55%) patients had liver involvements within the first 100 days after allo-HSCT. Baseline elastography was not predictive for the occurrence of overall liver abnormalities. A significant increase in 2D real-time shearwave elastography (2D-SWE) was found in patients with sinusoidal obstruction syndrome (SOS). Fifteen patients (10%) fulfilled EBMT score criteria and twelve (8%) reached Baltimore criteria for SOS diagnosis, but only six (4%) had a confirmed SOS. 2D-SWE at day+14 allowed early detection of SOS (AUROC=0.84, p=0.004) and improved sensibility (75%), specificity (99%) and positive predictive value (60%) over the Seattle, Baltimore or EBMT scores. A 2D-SWE measurement above 8.1kPa at day+14 after allo-HSCT seems a promising, non-invasive, and reproducible tool for early and accurate diagnosis of SOS.