Diagnosis of sinusoidal obstruction syndrome by positron emission tomography/computed tomography: Report of two cases treated by defibrotide


  • Mathieu Gauthé,

    Corresponding author
    1. Institut Curie, Service de Médecine Nucléaire, Department of Nuclear Medicine, Saint-Cloud, France
    • Address reprint requests to: Mathieu Gauthé, Institut Curie, Service de Médecine Nucléaire, 35 rue Dailly, Saint-Cloud, F-92210, France. E-mail: mathieu.gauthe@curie.fr; fax: +33147113378.

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  • Laurence Bozec,

    1. Institut Curie, Service d'Oncologie Médicale, Department of Medical Oncology, Saint-Cloud, France
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  • Pierre Bedossa

    1. Départment d'Anatomie Pathologique Beaujon-Bichat, Inserm U773, Université Paris-Diderot, Hôpital Beaujon, Clichy, France
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  • Potential conflict of interest: Nothing to report.


Sinusoidal obstruction syndrome (SOS) is a potentially fatal liver injury that mainly occurs after myeloablative chemotherapy. We report two cases of SOS investigated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and treated with defibrotide. (Hepatology 2014;60:1789–1791)


18F-fluorodeoxyglucose positron emission tomography / computed tomography


hematopoietic stem cell transplantation


sinusoidal obstruction syndrome


standardized uptake value


transjugular liver biopsy

Sinusoidal obstruction syndrome (SOS) generally occurs within 3 weeks after myeloablative chemotherapy.[1, 2] The reported incidence ranges from 5% to 70% depending on the conditioning regimen and risk factors such as previous exposure to cytotoxic agents.[1, 2] We report two patients with SOS treated with defibrotide in whom 18F-fluorodeoxyglucose positron emission tomography / computed tomography (FDG-PET/CT) demonstrated interesting findings.

Case Reports

Case 1

A 36-year-old man with brain tumor previously treated with chemotherapy followed by hematopoietic stem cell transplantation (HSCT) was investigated 2 months later by PET/CT scan, which revealed numerous disseminated lesions with increased FDG uptake in the liver corresponding to multiple hypodense lesions on CT, suggestive of metastases (standardized uptake value [SUV] peak = 2.7) (Fig. 1A). Clinical examination was normal. Laboratory work-up showed thrombocytopenia and slightly elevated transaminases (Table 1). Transjugular liver biopsy (TJLB) revealed SOS with moderate injury of sinusoidal endothelium and dilatation of the sinusoids, no hepatocyte necrosis, and only mild fibrin deposition in hepatic venules. Treatment with defibrotide was initiated, according to the protocol recommended by our national multidisciplinary meeting for vascular disorders of the liver: defibrotide is available through a strictly regulated compassionate-use program. Once approved, treatment is authorized for 2 weeks at a dose of 6.25 mg per kg body weight, with the possibility to apply for longer use if treatment is effective. No improvement of laboratory parameters was observed after 1 month of treatment. Follow-up PET/CT did not demonstrate any significant changes (Fig. 1B). Defibrotide was stopped and transaminases remained stable and slightly elevated. Thrombocytopenia did not improve and was attributed to chemotherapy-induced dysmyelopoiesis. The patient died from brain herniation due to progression of the primary tumor 3 months after completion of defibrotide therapy.

Figure 1.

PET (maximum intensity projection images) focused on the abdomen showing disseminated FDG hot spots in the liver before defibrotide (A) with no significant improvement after defibrotide (B) in case 1 (top); and diffusely increased hepatic activity before defibrotide (C) with complete normalization after defibrotide (D) in case 2 (bottom).

Case 2

A 51-year-old man with a Hodgkin's lymphoma presented with dyspnea and jaundice 2 weeks after HSCT. Clinical examination revealed significant hepatomegaly and anasarca. Laboratory work-up showed marked elevation of transaminases and bilirubin, thrombocytopenia and decreased clotting factors (Table 1). PET/CT showed diffusely increased hepatic activity (SUV peak = 3.3) (Fig. 1C). TJLB demonstrated SOS with severe destruction of sinusoidal endothelium, dilatation of the sinusoids (Fig. 2), hepatocyte necrosis, and obliterated hepatic venules. Treatment with defibrotide was initiated. Liver FDG uptake returned to normal after 1 month of treatment (SUV peak = 2.4, Fig. 1D), associated with complete clinical recovery and normalization of laboratory parameters.

Table 1. Comparison of Clinical, Laboratory, and Histologic Findings Between the Two Cases
 Case 1Case 2
Previous chemotherapy2 cycles of carboplatin and etoposide4 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD)
4 cycles of docosahexaenoic acid-oxaliplatin
HSCT conditioning regimenHigh-dose thiotepaHigh-dose carmustine, etoposide, cytarabine, and melphalan (BEAM)
Clinical examinationNormalDyspnea, Jaundice, Hepatomegaly, Generalized edema
Laboratory parameters  
AST/ALT (N: 6-40 IU/L)2-3xULN20xULN
Bilirubin (N<17)Normal190 micromol/l
Platelets (N>150,000/L)16,000/L16,000/L
Prothrombin time (N>70%)100%40%
Proconvertin (FVII) (N>70%)Normal22%
Sinusoidal endotheliumModerate alterationSevere destruction
Dilatation of sinusoidsModerate dilatationMajor dilatation
Appearance of hepatocytesNormalSevere necrosis
Hepatic venulesMild fibrin depositionObliterated
Figure 2.

Transjugular liver biopsy from patient 2 showing dilated sinusoids (black arrow). Hematoxylin-eosin-safran staining (magnification ×4).


SOS should be suspected in postmyeloablative chemotherapy patients who develop hepatomegaly, jaundice, and weight gain.[1, 2] While 70% of patients with mild/moderate SOS recover spontaneously, severe SOS usually leads to multiorgan failure and is associated with a high mortality rate.[1] No specific treatment for SOS is currently available. Defibrotide is an antithrombotic agent reported to improve symptoms and signs of SOS in 42% of patients.[3]

The diagnosis of SOS is established by liver biopsy, with histologic findings including endothelial cell damage, dilatation of the sinusoids, hepatocyte necrosis, and collagen deposition in the sinusoids, with subsequent liver fibrosis.[4] In hepatocytes, FDG is taken up by surface glucose transporter-2 expressed by the sinusoidal endothelium. The prevailing hypothesis of SOS pathophysiology focuses on damage to the hepatic venular and sinusoidal endothelium as an initial event that activates the coagulation cascade. The venular and sinusoidal lumen is reduced due to concentric subendothelial zone edema.[1, 5]

We suggest that PET findings in the liver could be explained by trapping of FDG in dilated sinusoids; FDG cannot enter hepatocytes due to destruction of the sinusoidal endothelium. An inflammatory reaction is a less likely hypothesis, as no inflammatory cells were observed on liver biopsy.

Interestingly, patient 2 presented more severe clinical features and histologic findings, but obtained complete recovery in response to treatment, while patient 1 had no significant clinical findings, only moderate damage on liver biopsy, and derived no benefit from treatment. Differences in sinusoidal injuries may be predictive of response to defibrotide, but this aspect requires further investigation.

In conclusion, FDG-PET/CT imaging may be a useful tool to assess the prognosis of SOS and the therapeutic efficacy of defibrotide, but further data need to be generated and validated by larger studies.