Sinusoidal obstruction syndrome (SOS), first reported by Jelliffe in 1954. In 1957, Stein discovered that the pathological mechanism of SOS is hepatic venules occlusion process, namely the thickening of the vessel wall caused by endophlebitis. Unlike classic BCS, there is no thrombosis in the hepatic vein or inferior vena cava. This occlusion may be partial or complete due to a centripetal intimal filling of the vessel wall due to endophlebitis. Early on the intima is severely swollen with edema, but later connective tissue forms. Occlusion of the veins causes intense central lobular congestion, which widens the venous sinuses, ruptures and forms a blood lake. The pressure of the blood lake causes necrosis of the surrounding hepatocytes. Finally, compensatory fibrosis alters the structure of the liver and develops into a centrilobular cirrhosis. . In recent years, it has been found that SOS damages the epithelial cells of sinusoids and hepatocytes in the 3 zones of hepatic acinus, and the shedding of endothelial cells leads to the occlusion of hepatic sinuses and terminal hepatic venules, while large hepatic veins were patent and there was a nonthrombotic occlusion of central and sublobular hepatic veins by subendothelial edema and fibrosis [12, 13]. In addition to endothelial cell shedding, blood flow obstruction is promoted by the proliferation of perisinusoidal stellate cells and subendothelial fibroblasts in the terminal hepatic vein followed by the deposition of the extracellular matrix. Then perivenular fibrosis spreads into the liver parenchyma . Triggers include high-dose chemotherapy, Inflammation and cytokines released by transplantation, release of endotoxin, alloreactivity, calcineurin inhibitor and so on. In addition to the above triggers, SOS risk also depends on the genetic predisposition of the patient and that development of SOS may be rapid and unpredictable .
In Western countries, SOS is now recognised as a complication most commonly associated with high-dose chemotherapy and stem cell transplantation . In recent years, more and more literature has been published on Gynura segetum induction of SOS, a kind of pyrrolizidine alkaloids containing herbal medicine widely used in China and some Asian countries [17, 18]. The parenchyma of this disease is blocked outflow from the sinusoidal and centrilobular vein, leading to liver congestion and enlargement, and is one of the three most common causes of death in bone marrow transplant patients. The current diagnosis is by reference to Seattle and Baltimore criteria and is based on clinical features including painful hepatomegaly, hyperbilirubinemia and fluid retention [1, 6]. The reported mortality of SOS varies from 20 to 50%. While there is a gradual resolution of symptoms in mild and moderate patients, the mortality of severe patients approaches 100%, often involving multiple organ failure (MOF). The patients who develop hyperbilirubinaemia and significant fluid retention earlier and worsen faster are at high risk of severe SOS . Clinical diagnosis needs to be rapid and accurate, because some patients will progress to MOF before diagnosis is clear, and the best opportunity for intervention will be lost. Although liver biopsy is the gold standard for diagnosis, it is often limited by thrombocytopenia, abnormal coagulation function and massive ascites . In addition, the heterogeneity distribution of lesions also affects the accuracy of biopsy . The decrease rate of total protein and albumin in SOS patients was higher than that of BCS, indicating that SOS patients suffered more serious liver function damage.
Liu et al. observed that different pathological features upon different stages by animal models of PAs-induced HSOS. In acute stage, sinusoidal congestion and dilation, the hepatocyte necrosis and the extravasation of erythrocytes in zone 3. In addition, macrophages infiltrated into the space of Disse, and engulfed erythrocytes. In sub-acute stage, pathologic examination showed complete loss of pericentral hepatocytes, sinusoidal dilatation, deposition of pigment granules . The varieties of pathological manifestations depend on age, the PAs dose, the period, and individual variation . BCS and congestive liver disease can also show sinusoidal congestion and hepatocyte necrosis, which are sometimes difficult to distinguish from histologically . Imaging techniques have experienced major progress since the 1980s and the initial definition of the criteria for diagnosis of SOS/VOD, raising the possibility that they may contribute to refining such diagnosis today . CT and MRI showed hepatomegaly, ascites, hepatic vein narrowing, gallbladder wall thickening, periportal edema, patchy signal enhancement of the liver. Zhou et al. reported that liver parenchyma surrounding the main hepatic veins demonstrated relatively normal enhancement compared to the rest of the patchy enhanced area of liver. This interesting finding is called "clover sign", suggest that the venules adjacent to the hepatic main vein are more likely to keep patent; the extent of abnormal patchy liver enhancement reflect the severity of the disease [20–24]. In present study, the SOS images showed that the enhancement distribution around the main hepatic vein was obvious, while the patchy enhancement was dominant in the BCS patients, which was related to the different pathogenesis, location and degree of liver parenchymal injury of the two diseases.
In practice, SOS is not only be distinguished from other rare cases of diffuse liver diseases, such as amyloidosis, glycogen storage disease, Wilson's disease and α-1antitrypsin deficiency, but also from the relatively rare BCS. BCS is a group of diseases characterized by partial or total hepatic veins outflow obstruction, with elevated sinusoidal pressure, portal hypertension, liver congestion, eventually hepatic fibrosis and cirrhosis [25, 26]. The clinical manifestation depends on the degree of venous obstruction and the patency of Intra- and extrahepatic collaterals. One quarter of patients have no underlying disease [27, 28]. Imaging findings included occlusion or compression of hepatic veins and/or inferior vena cava, formation of collateral circulation, caudate lobe enlargement, and delayed enhanced nodules formation . This study showed that there was a statistical difference between the two diseases in the Intra- and extrahepatic collaterals circulation, hepatic venous obstruction, parenchyma enhancement pattern, delayed phase enhances uniformity, and SOS caused more serious liver damage. In addition, SOS showed heterogeneous enhancement in the delayed phase of enhanced CT and/or MR, this is caused by sinusoidal or hepatic venule obstruction that is not or poorly enhanced. This kind of imaging manifestation also conforms to the pathological mechanism of the two diseases and can be used as one of the important imaging differentiation point of the two diseases.
It is difficult to obtain timely and reliable diagnosis by using the current clinical diagnostic criteria. Noninvasive imaging is becoming more and more important in SOS diagnosis and differential diagnosis. Combined with liver hemodynamic changes, liver parenchymal heterogeneity, damaged hepatocyte function, and portal hypertension imaging features provide important information for the identification of these diseases. The limitation of this study is that there are few subjects. Secondly, some patients presented thrombocytopenia and coagulation abnormalities and massive ascites, so histological evidence could not be obtained, which also limited the inclusion of more cases.