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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.

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OBJECTIVE AND BACKGROUND: Sinusoidal obstruction syndrome (SOS) is a life-threatening complication in hematopoietic stem cell transplantation (HSCT) patients. However, the related risk factors in pediatric and young adult HSCT recipients remain unclear. Thus, we conducted this meta-analysis to identify potential risk factors for SOS in children and young adults undergoing HSCT. METHOD: We acquired related articles through searching PubMed, EMBASE, and the Cochrane Library up to May 31, 2024. We calculated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to identify potential risk factors. RESULTS: A total of 12 studies with 7644 HSCT recipients were included. Bone marrow transplantation (OR = 1.35, 95% CI: 1.03-1.77, I2 = 0%), busulfan (BU) (OR = 3.63, 95% CI: 1.78-7.38, I2 = 70%), and fludarabine (FLU) (OR = 1.55, 95% CI: 1.09-2.21, I2 = 16%) were risk factors for SOS after HSCT in children and young adults. CONCLUSION: Bone marrow transplantation and the use of BU or FLU might be risk factors for SOS after HSCT in children and young adults.

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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.

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BACKGROUND: Liver injury post allogeneic hematopoietic stem cell transplantation (Allo-HSCT), particularly first-time occurrences, is a prevalent and severe complication. METHODS: Clinical data from 262 patients treated at 3 medical centers in Shenzhen, China, between January 2018 and December 2021 were retrospectively collected. Risk factors and outcomes of initial liver injury post allo-HSCT were analyzed. RESULTS: Liver injury occurred in 70.8% of patients, with drug-induced liver injury (DILI) being the most common cause. Other causes included graft-versus-host disease (GVHD) and veno-occlusive disease (VOD). Pre-transplant HBsAg positivity was a significant risk factor. Differences in the timing and survival outcomes were observed among patients with different causes and types of liver injury. Patients with VOD or hepatic aGVHD had lower overall survival compared to those with DILI or hepatic cGVHD. Patients with isolated enzyme elevation had a more favorable prognosis than those with isolated bilirubin elevation or simultaneous enzyme and bilirubin elevation. CONCLUSION: Findings of our study serve as a crucial resource for clinicians, assisting in the challenging task of diagnosing and managing liver injuries after allo-HSCT, especially when it occurs for the first time, which may ultimately help to reduce early treatment-related mortality and enhance the long-term survival of transplant recipients.

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BACKGROUND: The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options. METHODS: The HSOS murine model was induced by gavage of monocrotaline (MCT). An analysis of 16S ribosomal DNA (16S rDNA) of the feces was conducted to determine the composition of the fecal microbiota. Macrophage clearance, fecal microbiota transplantation (FMT), and butyrate supplementation experiments were used to assess the role of intestinal flora, gut barrier, and macrophage activation and to explore the relationships among these three variables. RESULTS: Activated macrophages and low microflora diversity were observed in HSOS patients and murine models. Depletion of macrophages attenuated inflammatory reactions and apoptosis in the mouse liver. Moreover, compared with control-FMT mice, the exacerbation of severe liver injury was detected in HSOS-FMT mice. Specifically, butyrate fecal concentrations were significantly reduced in HSOS mice, and administration of butyrate could partially alleviated liver damage and improved the intestinal barrier in vitro and in vivo. Furthermore, elevated lipopolysaccharides in the portal vein and high proportions of M1 macrophages in the liver were also detected in HSOS-FMT mice and mice without butyrate treatment, which resulted in severe inflammatory responses and further accelerated HSOS progression. CONCLUSIONS: These results suggested that the gut microbiota exacerbated HSOS progression by regulating macrophage M1 polarization via altered intestinal barrier function mediated by butyrate. Our study has identified new strategies for the clinical treatment of HSOS.

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Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication which can develop after haemopoietic stem cell transplantation (HSCT) and some antibody-drug conjugates. Several SOS/VOD diagnostic and management guidelines exist, with the most recent and refined being the European Society for Blood and Marrow Transplantation adult and paediatric guidelines. Timely diagnosis and effective management (including the availability of therapeutic options) significantly contribute to improved patient outcomes. In Australia and New Zealand, there is variability in clinical practice and access to SOS/VOD therapies. This review aims to summarise the current evidence for SOS/VOD diagnosis, prevention and treatment and to provide recommendations for SOS/VOD in the context of contemporary Australasian HSCT clinical practice.

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Portal hypertension (PHT) is defined as an increase in pressure at the level of the portal vein above 5 mmHg, the most common cause being liver cirrhosis. Among the presinusoidal intrahepatic causes of PHT with portal venular involvement, what was traditionally known as idiopathic non-cirrhotic portal hypertension (NCIH) is described, with the requirements of excluding those patients who did not present PHT, as well as those with the presence of liver cirrhosis and thrombosis. portal venous vein (PVT). Currently, the diagnostic criteria for this entity have been reconsidered, and its name, being known as porto-sinusoidal vascular disease (PSVD), also does not exclude patients with PHT or the presence of underlying liver disease. Liver biopsy continues to be the gold standard for diagnosis. The clinical manifestations are derived from PHT and the management is similar to the complications that occur in patients with liver cirrhosis. The case of a male patient is presented who presents with symptoms of digestive bleeding, with findings of esophageal varices in upper endoscopy in addition to a study of viral, autoimmune liver disease and negative deposits, with a conclusive liver biopsy of porto-sinusoidal vascular disease.

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Hepatic sinus obstruction syndrome (HSOS) is easy to be misdiagnosed or missed, and there is no unified and effective treatment for it. A patient was considered to have Budd-Chiari syndrome. He underwent a transjugular liver biopsy, and pathological examination revealed HSOS without liver cirrhosis. After the failure of anticoagulation therapy, he successfully received a transjugular intrahepatic portosystemic shunt (TIPS). After discharge, he was followed-up for four years with a good prognosis. G. segetum-induced HSOS can be easily overlooked, especially in patients with underlying liver diseases. When medical therapy fails, TIPS can control ascites and portal hypertension, and the long-term prognosis is optimistic.

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Advancements in surgical techniques and the optimization of immunosuppression have boosted organ transplant survival rates; however, liver transplant recipients still risk complications such as hepatic vein occlusive disease (HVOD), also called sinusoidal obstruction syndrome. Rare but potentially fatal HVOD damages endothelial cells due to factors like chemotherapy, stem cell transplantation, and certain medications such as azathioprine and tacrolimus. Typically, HVOD presents with distinct clinical symptoms, including ascites, jaundice, and significant weight gain. Herein, we present the case of a 66-year-old male with decompensated liver cirrhosis due to hepatitis C virus infection. The patient underwent a deceased donor liver transplantation at our center. Unfortunately, 4 months after the transplant, he experienced progressive dyspnea and developed right pleural effusion. Abdominal computed tomography and a liver biopsy confirmed the diagnosis of HVOD, likely induced by tacrolimus. After stopping tacrolimus, we observed a significant decrease in ascites and remission of the patient's clinical symptoms of abdominal distention and dyspnea; subsequently, we introduced cyclosporine. In this report, we describe this specific patient's case and discuss HVOD, including its diagnosis and management.

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Porto-sinusoidal vascular disease (PSVD) is the medical diagnosis for a patient who has portal hypertension in the absence of cirrhosis on liver biopsy. There are several specific histologic findings for PSVD, including obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. Epidemiologic reports vary widely among regions; PSVD comprises less than 10% of causes of portal hypertension in Western countries but incidence has been found to be as high as 48% in India. There is an expansive list of etiologies that have been reported to cause PSVD.

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Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT). However, its characterization after haploidentical HSCT (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) is scarce. This study aimed to describe characteristics and outcomes of patients with SOS/VOD after haplo-HSCT with PT-Cy. We conducted a retrospective study of 797 patients undergoing a haplo-HSCT with PT-Cy between 2007 and 2019 in 9 centers in Spain. SOS/VOD was defined according to modified Seattle, Baltimore, or revised European Society for Blood and Marrow Transplantation (EBMT) criteria. Severity was graded retrospectively according to revised EBMT severity criteria into 4 categories: mild, moderate, severe, and very severe. From a total of 797 haplo-HSCTs performed, 46 patients (5.77%) were diagnosed with SOS/VOD at a median of 19 days (range, 4 to 84 days) after transplantation. Based on revised EBMT severity criteria, the SOS/VOD cases were classified as mild (n = 4; 8.7%), moderate (n = 10; 21.7%), severe (n = 12; 26.1%), and very severe (n = 20; 43.5%). Overall, 30 patients (65%) achieved SOS/VOD complete response, 25 (83%) of whom were treated with defibrotide. Twenty patients (43%) died before day +100 post-HSCT. Death was attributed to SOS/VOD in 11 patients, and 5 patients died of other causes without resolution of SOS/VOD. The incidence of SOS/VOD after haplo-HSCT with PT-Cy was comparable to those reported after HLA-identical HSCT series. Most of the patients developed very severe SOS/VOD according to revised EBMT severity criteria. Despite a promising SOS/VOD complete response (CR) rate (65%), 100-day mortality remained high (43%), indicating that further improvement in the management of this potentially fatal complication is needed.

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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.

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Thiopurine-methyltransferase (TPMT) and nudix-hydrolase-15 (NUDT15) are enzymes relevant to the metabolism of thiopurine medications, used to treat immunologic disorders and malignancies. Standard dosing administered in the setting of TPMT/NUDT15 dysfunction can cause excessive cytotoxic metabolites and life-threatening complications. We describe an adolescent with high-risk B-cell acute lymphoblastic leukemia (ALL) whose TPMT/NUDT15 status was unknown due to lack of insurance approval for genetic testing. He subsequently developed myelosuppression and severe veno-occlusive disease (VOD) after receiving 6-mercaptopurine (6-MP). Our patient provides an example of a very rare 6-MP-related toxicity and the potential benefit of TPMT/NUDT15 screening before initiating thiopurine therapy.

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INTRODUCTION: Hepatic veno-occlusive disease (VOD) is a critical medical emergency with a high mortality rate of up to 90% if not promptly treated. Defibrotide is the only approved medication for VOD treatment, exhibiting anti-inflammatory, antithrombotic, and anti-ischemic properties. This report presents a case of severe VOD in a patient undergoing acute lymphoblastic leukemia (ALL) treatment. CASE PRESENTATION: We describe the successful and rapid treatment of severe VOD in an ALL patient using therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and methylprednisolone (MPZ). The patient showed significant clinical and laboratory improvement after this combined therapeutic approach. CONCLUSION: This case highlights the effectiveness of TPE, IVIG, and MPZ in the treatment of severe VOD in ALL patients, providing insights into alternative therapeutic strategies in the absence of Defibrotide.

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Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism. In present study, cholic acid species (namely, cholic acid, taurine conjugated-cholic acid, and glycine conjugated-cholic acid) were identified as the candidate biomarkers (area under the ROC curve 0.968 [95% CI 0.908-0.994], sensitivity 83.87%, specificity 96.55%) for PA-HSOS using two independent cohorts of patients with PA-HSOS. The increased primary bile acid biosynthesis and decreased liver expression of farnesoid X receptor (FXR, which is known to inhibit bile acid biosynthesis in hepatocytes) were highlighted in PA-HSOS patients. Furtherly, a murine PA-HSOS model induced by senecionine (50 mg/kg, p.o.), a hepatotoxic PA, showed increased biosynthesis of cholic acid species via inhibition of hepatic FXR-SHP singling and treatment with the FXR agonist obeticholic acid restored the cholic acid species to the normal levels and protected mice from senecionine-induced HSOS. This work elucidates that increased levels of cholic acid species can serve as diagnostic biomarkers in PA-HSOS and targeting FXR may represent a therapeutic strategy for treating PA-HSOS in clinics.

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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.

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Hepatic sinusoidal obstruction syndrome (HSOS) is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids (PAs) and hematopoietic stem cell transplantation (HSCT) treatment, resulting in severe liver dysfunction, multiple organ failure, and even death. Hepatic sinusoidal dilatation and obstruction, hepatocyte coagulative necrosis, and hepatic lobular inflammation are the main pathological manifestations of HSOS. The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells (LSECs). Currently, it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms, and secondary coagulation and fibrinolysis disorders, oxidative stress, and inflammatory responses are the occurrence contributors to HSOS; however, the mechanism has not been fully elucidated. Therefore, the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage. This article provides an overview of the epidemiology, etiology, and pathological changes of HSOS and reviews the physiological functions, common etiological damage mechanisms, and the key role of LSEC damage in the pathogenesis of HSOS, with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years. Furthermore, we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.

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Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a rare but potentially fatal complication following allogenic hematopoietic cell transplantation (allo-HCT). Timely identification of SOS/VOD to allow for prompt treatment is critical, but identifying a VOD-predictive biomarker remains challenging. Given the pivotal role of endothelial dysfunction in SOS/VOD pathophysiology, the CECinVOD study prospectively evaluated levels of circulating endothelial cells (CECs) in patients undergoing allo-HCT with a myeloablative conditioning (MAC) regimen to investigate the potential of CEC level in predicting and diagnosing SOS/VOD. A total of 150 patients from 11 Italian bone marrow transplantation units were enrolled. All participants were age >18 years and received a MAC regimen, putting them at elevated risk of developing SOS/VOD. Overall, 6 cases of SOS/VOD (4%) were recorded. CECs were detected using the Food and Drug Administration-approved CellSearch system, an immunomagnetic selection-based platform incorporating ferrofluid nanoparticles and fluorescent-labeled antibodies, and were defined as CD146+, CD105+, DAPI+, or CD45-. Blood samples were collected at the following time points: before (T0) and at the end of conditioning treatment (T1), at neutrophil engraftment (T2), and at 7 to 10 days postengraftment (T3). For patients who developed VOD, additional samples were collected at any suspected or proven VOD onset (T4) and weekly during defibrotide treatment (T5 to T8). A baseline CEC count >17/mL was associated with an elevated risk of SOS/VOD (P = .04), along with bilirubin level >1.5 mg/mL and a haploidentical donor hematopoietic stem cell source. Postconditioning regimen (T1) CEC levels were elevated (P = .02), and levels were further increased at engraftment (P < .0001). Additionally, patients developing SOS/VOD after engraftment, especially those with late-onset SOS/VOD, showed a markedly higher relative increase (>150%) in CEC count. Multivariate analysis supported these findings, along with a high Endothelial Activation and Stress Index (EASIX) score at engraftment (T2). Finally, CEC kinetics corresponded with defibrotide treatment. After the start of therapy (T4), CEC levels showed an initial increase in the first week (T5), followed by a progressive decrease during VOD treatment (T6 and T7) and a return to pre-SOS/VOD onset levels at resolution of the complication. This prospective multicenter study reveals a low incidence of SOS/VOD in high-risk patients compared to historical data, in line with recent reports. The results from the CECinVOD study collectively confirm the endothelial injury in allo-HCT and its role in in the development of SOS/VOD, suggesting that CEC level can be a valuable biomarker for diagnosing SOS/VOD and identifying patients at greater risk of this complication, especially late-onset SOS/VOD. Furthermore, CEC kinetics may support treatment strategies by providing insight into the optimal timing for discontinuing defibrotide treatment.

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Sinusoidal Obstructive Syndrome (SOS) is a life-threatening complication after hematopoietic stem-cell transplantation (HSCT), characterized by post-sinusoidal portal hypertension. FibroScan is used to assess portal hypertension non-invasively. We assessed transient elastography (TE) applicability in diagnosing SOS. The study included 27 adult patients, 11 underwent TE for high SOS risk pre-HSCT, 17 underwent TE post-HSCT due to bilirubin ≥2 mg/dl with no definite diagnosis of SOS. The first group had median Liver Stiffness Measurement (LSM) of 7.4 kPa (range, 3.3-22.5). Based on LSM results, conditioning regimen was modified for six patients and two of them developed SOS. Only one patient who did not have protocol adjustment experienced SOS. No patient with LSM < 7 kPa developed SOS. The second group had median LSM of 7.7 kPa (4.4-31.5). Median LSM after HSCT was significantly higher in patients who subsequently developed established SOS (n = 10) compared to patients who did not (n = 8), with values of 10.7 kPa (5.6-31.5) and 5.9 kPa (4.4-13.8), respectively (p = 0.02). An LSM cut-off of 7.5 kPa had a sensitivity and specificity of 75 and 80% for diagnosing SOS. In conclusion, pre-HSCT LSM can help adjustment of conditioning regimen in patients with high-risk for SOS. Post-HSCT LSM can help in early diagnosis of SOS.

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