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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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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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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 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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Sinusoidal obstructive syndrome (SOS), or veno-occlusive disease, of the liver has been recognized as a complex, life-threatening complication in the posthematopoietic stem cell transplant (HSCT) setting. The diagnostic criteria for SOS have evolved over the last several decades with a greater understanding of the underlying pathophysiology, with 2 recent diagnostic criteria introduced in 2018 (European Society of Bone Marrow Transplant [EBMT] criteria) and 2020 (Cairo criteria). We sought out to evaluate the performance characteristics in diagnosing and grading SOS in pediatric patients of the 4 different diagnostic criteria (Baltimore, Modified Seattle, EBMT, and Cairo) and severity grading systems (defined by the EBMT and Cairo criteria). Retrospective chart review of children, adolescent, and young adults who underwent conditioned autologous and allogeneic HSCT between 2017 and 2021 at a single pediatric institution. A total of 250 consecutive patients underwent at least 1 HSCT at UCSF Benioff Children's Hospital San Francisco for a total of 307 HSCT. The day 100 cumulative incidence of SOS was 12.1%, 21.1%, 28.4%, and 28.4% per the Baltimore, Modified Seattle, EBMT, and Cairo criteria, respectively (P < .001). We found that patients diagnosed with grade ≥4 SOS per the Cairo criteria were more likely to be admitted to the Pediatric Intensive Care Unit (92% versus 58%, P = .035) and intubated (85% versus 32%, P = .002) than those diagnosed with grade ≥4 per EBMT criteria. Age <3 years-old (HR 1.76, 95% [1.04 to 2.98], P = .036), an abnormal body mass index (HR 1.69, 95% [1.06 to 2.68], P = .027), and high-risk patients per our institutional guidelines (HR 1.68, 95% [1.02 to 2.76], P = .041) were significantly associated with SOS per the Cairo criteria. We demonstrate that age <3 years, abnormal body mass index, and other high-risk criteria associate strongly with subsequent SOS development. Patients with moderate to severe SOS based on Cairo severity grading system may correlate better with clinical course based on ICU admissions and intubations when compared to the EBMT severity grading system.

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Hepatic veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS) is a severe complication that can occur following haematopoietic stem cell transplant (HSCT) with high-intensity conditioning chemotherapy regimens. Severe VOD/SOS, often characterised by multiorgan failure, is associated with a high mortality rate. This case report details the complex clinical course of a male patient in his mid-20s, recently diagnosed with B cell acute lymphoblastic leukaemia, who underwent allogeneic HSCT. Based on the 2023 European Society for Blood and Marrow Transplantation (EBMT) criteria, the patient developed very severe VOD/SOS, prompting immediate treatment with defibrotide. Unexpectedly, he developed profound hyperammonaemia exceeding 900 µmol/L, leading to encephalopathy and cerebral oedema. Despite aggressive interventions including defibrotide, lactulose, rifampin and haemodialysis, the patient passed away due to cerebral oedema and pulseless electrical activity arrest. We theorise the hyperammonaemia is disproportionate to his hepatic dysfunction and is possibly secondary to an acquired defect of the urea synthesis consistent with idiopathic hyperammonaemia, a rare complication in patients receiving intense conditioning chemotherapy.

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RATIONALE: Hepatic sinusoidal obstruction syndrome (HSOS), which includes hepatic stasis and portal hypertension, is a rare vascular disorder of the liver. It is often associated with hematopoietic stem cell transplantation. It is also possible to treat this disease using Chinese herbal medicines that contain pyrrolizidine alkaloids (PAs). This disease is extremely rare in children and poses a serious threat to their health. To our knowledge, this is the first case of HSOS in a child with PAs. PATIENT CONCERNS: We report a 4-year-old boy suffering from abdominal pain, hepatomegaly, massive ascites, elevated liver enzyme level, and severe portal hypertension as a result of the consumption of Gynura segetum (also known as Tusanqi in Chinese, a traditional herbal medicine containing PAs). DIAGNOSES: The child was finally diagnosed with PA-HSOS based on pathological diagnosis and imaging examination. INTERVENTION: With active symptomatic and supportive care and sequential anticoagulation therapy, the abdominal distension and liver function improved in the patient. OUTCOMES: The patient was eventually recovered. The levels of liver enzymes, hemoglobin, and bilirubin were normal, and the international normalized ratio fluctuated between 2.0 and 3.0 during 1-year follow-up after discharge. LESSONS: This case report emphasizes the prevention of Chinese herb-induced liver injury in children and the importance of active long-term sequential anticoagulant therapy to reduce the progressive damage of PA-HSOS in the liver.

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This study aimed to analyze the clinical characteristics of Gynura segetum (Tusanqi)-induced hepatic sinusoidal obstruction syndrome (HSOS) and the benefits and risks of anticoagulant therapy for Tusanqi-induced HSOS. This was a retrospective analysis of 49 patients with Tusanqi-induced HSOS who were treated with anticoagulation or standard therapy between July 2006 and December 2022. Clinical manifestations included abdominal pain (n = 47) and peritoneal or pleural effusion (n = 46); 2 patients died. Nineteen patients requested standard medical treatment, while 30 were treated with anticoagulants. HSOS resolved within 6 months in 22 patients but did not resolve in 27 patients. The resolution rate was higher in the anticoagulant than standard treatment group (P = .037). Logistic regression analysis revealed that a history of chronic liver disease or treatment increased the risk of poor outcomes. Bleeding complications occurred in 6 patients in the anticoagulant treatment group. Early diagnosis and anticoagulant treatment are beneficial for rapid recovery after Tusanqi-induced HSOS. However, anticoagulant treatment is associated with the risk of multisite bleeding.

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PURPOSE: Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication following hematopoietic stem cell transplantation (HSCT) in which early diagnosis improves patient outcome. The aim of our study was to detect laboratory parameters following HSCT that can predict the occurrence of SOS. METHODS: This retrospective study included 182 children, adolescents, and young adults who underwent allogeneic or autologous HSCT for the first time (median age 7.2 years). The diagnosis of SOS was based on the pediatric criteria of European Society for Blood and Marrow Transplantation (EBMT). We investigated 15 laboratory parameters after HSCT before the onset of SOS. RESULTS: The overall incidence of SOS was 14.8%. SOS developed in 24 of 126 allogeneic (19.1%) and in 3 of 56 autologous (5.4%) HSCT patients at a median time of 13 days after HSCT. We observed a low SOS mortality rate of 11.1% within 100 days after HSCT. International normalized ratio (INR) ≥ 1.3, activated partial thromboplastin time (aPTT) ≥ 40 s, reptilase time ≥ 18.3 s, factor VIII ≤ 80%, antithrombin III ≤ 75%, protein C ≤ 48%, D-dimer ≥ 315 µg/L, bilirubin ≥ 9 µmol/L, and ferritin ≥ 3100 µg/L showed significant associations with the onset of SOS in the univariate analyses. In the multivariate analysis, INR ≥ 1.3 [odds ratio (OR) = 8.104, p = 0.006], aPTT ≥ 40 s (OR = 10.174, p = 0.001), protein C ≤ 48% (OR = 5.215, p = 0.014), and ferritin ≥ 3100 µg/L (OR = 7.472, p = 0.004) could be confirmed as independent risk factors after HSCT before SOS. If three of the four significant cut-off values were present, the probability of developing SOS was more than 70%. The probability of SOS was 96%, if all four laboratory parameters were changed according to the cut-off values. The values of factor XIII, von Willebrand factor (vWF), von Willebrand factor activity (vWF activity), protein S, fibrinogen, and alanine aminotransferase (ALT) were not relevant for the occurrence of SOS. CONCLUSION: In summary, the laboratory parameters INR, aPTT, protein C, and ferritin were very useful to predict the occurrence of SOS. In addition, this is the first report on a significant association between SOS and high values of INR and aPTT after HSCT before SOS.

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Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis of SOS/VOD is associated with improved clinical outcomes. In 2023, the refined European Society for Blood and Marrow Transplantation diagnostic and severity criteria (refined EBMT criteria 2023) have been advocated. The revision has introduced new diagnostic categories, namely; probable, clinical, and proven SOS/VOD. In addition, the Sequential Organ Failure Assessment (SOFA) score has been newly incorporated into the SOS/VOD severity grading. We performed a retrospective analysis to evaluate the utility of these criteria. We analyzed 161 cases who underwent allogeneic HSCT. We identified 53 probable, 23 clinical, and 4 proven SOS/VOD cases. Probable SOS/VOD was diagnosed a median of 5.0 days earlier (interquartile range: 2-13 days, P < 0.001) than that of clinical SOS/VOD. The development of probable SOS/VOD alone was associated with a significantly inferior survival proportion compared to non-SOS/VOD (100-day survival, 86.2% vs. 94.3%, P = 0.012). The SOFA score contributed to the prediction of prognosis. Consequently, the refined EBMT criteria 2023 demonstrated the utility of SOS/VOD diagnosis and severity grading. Further investigations and improvements in these criteria are warranted.

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Sinusoidal obstruction syndrome (SOS) is a serious liver disorder that occurs after liver transplantation, hematopoietic stem cell transplantation, and the administration of anticancer drugs. Since SOS is a life-threatening condition that can progress to liver failure, early detection and prompt treatment are required for the survival of patients with this condition. In this study, female CD1 mice were divided into treatment and control groups after the induction of an SOS model using monocrotaline (MCT, 270 mg/kg body weight intraperitoneally). The mice were analyzed at 0, 12, 24, and 48 h after MCT administration, and blood and liver samples were collected for assays and histopathology tests. SOS was observed in the livers 12 h after MCT injection. In addition, immunohistochemical findings demonstrated CD42b-positive platelet aggregations, positive signals for von Willebrand factor (VWF), and a disintegrin-like metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) in the MCT-exposed liver sinusoid. Although ADAMTS13's plasma concentrations peaked at 12 h, its enzyme activity continuously decreased by 75% at 48 h and, inversely and proportionally, concentrations in the VWF-A2 domain, in which the cleavage site of ADAMTS13 is located, increased after MCT injection. These findings suggest that the plasma concentration and activity of ADAMTS13 could be useful biomarkers for early detection and therapeutic intervention in patients with SOS.

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The current incidence, diagnostic policy, management, and outcome of VOD/SOS at EBMT centers were studied. All centers that had performed allogeneic HSCTs in adult patients within one defined year were invited to the study. Seventy-one centers participated with a total of 2886 allogeneic transplantations and 93 cases of VOD/SOS in 2018. The cumulative incidence of VOD/SOS at day 21 was 1.8% and at day 100 2.4%. Of 67 cases with detailed data, 52 were classical and 15 (22%) late onset (>day 21). According to the EBMT criteria, 65/67 patients had at least two VOD/SOS risk factors. The severity grades were: mild 0, moderate 3, severe 29, very severe 35. Fifty-four patients were treated with defibrotide. VOD/SOS resolved in 58% of the patients, 3/3 with moderate, 22/28 with severe, and 12/33 with very severe grade (p < 0.001). By day 100, 57% of the patients were alive; 3/3 with moderate, 22/29 with severe, and 13/35 with very severe VOD/SOS (p = 0.002). In conclusion, the incidence of VOD/SOS was low. Severe and very severe grades dominated. Very severe grade predicted poor outcome compared to severe grade further supporting the concept of early diagnosis and treatment to avoid a dismal outcome.

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Hematopoietic stem cell transplantation is used to treat a variety of hematologic malignancies and autoimmune conditions. The immunosuppressive medications as well as other therapies used both before and after transplantation leave patients susceptible to a wide spectrum of complications, including liver injury. Causes for liver damage associated with stem cell transplantation include sinusoidal obstruction syndrome, graft-versus-host disease, iron overload, and opportunistic infection. Here, the authors review the clinical and pathological findings of these etiologies of liver injury and provide a framework for diagnosis.

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PURPOSE: Pyrrolidine alkaloids-related hepatic sinusoidal obstruction syndrome (PA-HSOS) is associated with a high mortality rate without standardized therapy. The efficacy of transjugular intrahepatic portosystemic shunts (TIPS) remains controversial. The study aimed to explore the risk factors influencing the clinical response in patients with PA-HSOS related to Gynura segetum (GS) to assess the disease prognosis at an early stage and to evaluate the efficacy of TIPS in these patients. METHODS: This study retrospectively enrolled patients diagnosed with PA-HSOS between January 2014 and June 2021 with a clear history of exposure to GS. Univariate and multivariate logistic regression analyses were used to evaluate the risk factors influencing the clinical response in patients with PA-HSOS. Propensity score matched (PSM) was performed to compensate for differences in baseline characteristics between patients with and without TIPS. The primary outcome was the clinical response defined as the disappearance of ascites with normal total bilirubin levels and/or a reduction of elevated transaminase levels < 50% within 2 weeks. RESULTS: A total of 67 patients were identified in our cohort with a clinical response rate of 58.2%. Of these, thirteen patients were assigned to the TIPS group and 54 to the conservative treatment group. Logistic regression analysis revealed that TIPS treatment (P = 0.047), serum globulin levels (P = 0.043), and prothrombin time (P = 0.001) were independent factors influencing clinical response. After PSM, there was a higher long-term survival rate of patients (92.3% vs. 51.3%, P = 0.021) and a shorter hospital stay (P = 0.043), but a high trend in hospital costs (P = 0.070) in the TIPS group. The 6-month survival probability in patients undergoing TIPS therapy was more than ninefold higher than in patients without receiving that treatment [hazard ratio (95% CI) = 9.304 (4.250, 13.262), P < 0.05]. CONCLUSIONS: TIPS therapy may be an effective treatment option for patients with GS-related PA-HSOS.

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