1. BUDD-CHIARI SYNDROME AND SINUSOIDAL OBSTRUCTION SYNDROME
(HEPATIC VENOOCCLUSIVE DISEASE)

2. BCS is by consensus characterized by obstruction of the hepatic venous outflow tract, regardless of the mechanism and level of obstruction, but excluding cardiac and pericardial disease.
SOS is characterized by non-thrombotic obliteration of the sinusoids or central veins (or both), most often in the context of toxic exposure. Although the manifestations of these two vascular disorders may be similar, their epidemiology, cause, and therapy differ.

3. Budd-Chiari Syndrome Epidemiology
In Denmark, 0.5 per million inhabitants per year. In Japan 0.2 prevalence rate 2.4 per million inhabitants. In France 0.4 per million per year.
The level of obstruction differs according to geographic region: pure or combined obstruction of the inferior vena cava (IVC) predominated in Asian countries, whereas pure obstruction of the hepatic veins appears to predominate in Western countries.

4. Causes and Risk Factors
Primary BCS when the obstruction is the result of an endoluminal venous lesion (e.g., thrombosis, stenosis) and secondary when the obstruction is due to compression or invasion by a lesion originating outside the vein (e.g., tumor, cyst).

5. Secondary budd-chiari syndrome
Hepatocellular carcinoma (HCC).
Renal and adrenal adenocarcinoma.
Renal angiomyolipoma.
Primary hepatic hemangiosarcoma.
Epithelioid hemangioendothelioma.
Sarcoma of the IVC.
right atrial myxoma.
Intrahepatic cholangiocarcinoma.

6. Secondary budd-chiari syndrome
Alveolar hydatid disease.
Benign tumors (focal nodular hyperplasia FNH).
Abscesses and parasitic.
Compression or kinking of the hepatic veins may occur after liver transplantation or resection.
Blunt abdominal trauma may induce BCS in several ways: compression of the veins by hematoma or thrombosis of the hepatic veins or IVC.

7. Primary budd-chiari syndrome
MPDs are chronic clonal hematopoietic stem cell disorders characterized by proliferation of one or more of the myeloid lineages (i.e., granulocyte, erythroid, megakaryocyte).
In BCS patients, hemodilution and hypersplenism may mask the changes in peripheral blood cell counts that are considered essential for a diagnosis of MPD.
The combination of a platelet count higher than 200 × 109/L and marked enlargement of the spleen is highly predictive of MPD in patients with BCS.

8. A specific acquired mutation (V 617F) in the autoregulatory JH2 pseudokinase domain of the JAK2 gene can be detected in approximately 90% of patients with polycythemia vera and 50% of patients with essential thrombocythemia or myelofibrosis.
This mutation confers constitutive kinase activity, which causes enhanced hematopoiesis independent of growth factors (e.g., erythropoietin).
In patients testing negative, bone marrow biopsy should then be performed to ascertain the presence of MPD.

9. When combining the results of bone marrow biopsy and testing for the V617F JAK2 mutation MPD has been found in 40% to 50% of BCS patients.
Treatment of MPD
Hydroxyurea and low-dose aspirin).
Pegylated interferon alfa( decrease the percentage of mutated JAK2 alleles in 89% of treated patients).
New selective JAK1/JAK2 inhibitors are also very promising therapeutics, with clinical response obtained in 50% to 70% of patients with polycythemia vera and essential thrombocythemia.

10. APLS is characterized by arterial or venous thrombotic events (or both) or obstetric complications and a medium to high titer of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, or anti- β2-glycoprotein 1 antibodies).
APLS is found in 20% to 25% of patients with BCS. Among APLS patients with BCS, 40% have the secondary form of APLS which is associated with systemic lupus erythematosus or other connective tissue diseases, and 60% have the primary form, in which connective tissue disease is not present.

11. In patients with APLS, deep venous thrombosis, and no additional risk factors, the targeted (INR) for anticoagulation therapy is And (INR) 3 in patients who have recurrent thromboembolic events.
PNH is diagnosed by hemolytic anemia, marrow failure, and episodes of venous thrombosis, mainly in the cerebral and splanchnic territories. PNH is related to a somatic mutation in the phosphatidylinositol glycan class A, X-linded gene, which is responsible for a deficiency in glycosylphosphatidylinositol-anchored proteins (GPI-APs) that leads to hemolysis.

12. Flow cytometry allows direct quantification of GPI- AP-deficient cells with the use of anti-CD59 and anti- CD55 antibodies.
Risk factors for thrombosis include older age, thrombosis at diagnosis, and transfusions. The risk for fatal hemorrhage in patients with PNH is substantial and is mainly due to the frequent occurrence of thrombocytopenia.

13. The prevalence of BCS in PNH is approximately 10% to 15%. Therapy:
Anticoagulation therapy.
(TIPS).
Allogeneic stem cell transplantation.
Exulizumab is a humanized monoclonal antibody against terminal complement protein C5 that inhibits activation of the terminal complement. It has been shown to decrease hemolysis and thrombosis

14. Behçet disease accounts for less than 5% of cases of BCS in Western countries. More than 80% of affected patients have IVC involvement with or without extension to the hepatic veins. Treatment includes anticoagulation and immunosuppressive therapy.
Celiac disease, and Crohn disease (ulcerative colitis) have been associated with BCS in small case series.
An association between BCS with hypereosinophilic syndrome. Endothelial toxicity of eosinophil constituents has been incriminated.

15. Idiopathic granulomatous venulitis
Idiopathic granulomatous venulitis . The criteria for a diagnosis of sarcoidosis were fulfilled in some but not all cases. Therapy: corticosteroids.
Factor V Leiden and the prothrombin gene mutation are gain-of-function mutations that are cured by liver transplantation. The consequence of heterozygous or homozygous factor V Leiden mutation is resistance to activated protein C, which is found in about 25% of patients with BCS.

16. Diagnosis of factor V Leiden mutation is ruled out by a normal result on a test for activated protein C resistance.
Confirmation of an abnormal test result is obtained by molecular biology.
The G20210A mutation in the prothrombin gene is responsible for increased plasma levels of prothrombin and a moderate increase in the risk for venous thrombosis.
The diagnosis is made by molecular biology.

17. Antithrombin, protein C, and protein S are produced by the liver, and their plasma levels are nonspecifically decreased in many patients with BCS. These three inherited thrombophilias are cured by transplantation of a liver from an unaffected donor.
Impaired fibrinolysis and increased plasma levels of factor VII, factor VIII, or homocysteine are established risk factors for venous thrombosis. Genetic variations in the thrombin-activatable fibrinolysis inhibitor (TAFI) were shown to be associated with increased risk for hepatic or portal venous thrombosis, t Hyperhomocysteinemia was more prevalent in patients with BCS than in controls (37% vs. 18%).

18. The role of oral contraceptives are a risk factor for BCS is still controversial.
There is evidence in Nepal that extreme poverty is a strong risk factor for the development of BCS related to obstruction of the IVC. The mechanisms that underlie this association are still unknown

19. Screening for causes
Patients with newly recognized BCS should undergo appropriate investigations.
First to rule out a cause of secondary BCS.
Second to seek clinical evidence of systemic or gastrointestinal disease.
Third to routinely check for risk factors for thrombosis

20. Pathophsiology and histopathology of liver damage
Obstruction of a single main hepatic vein is clinically silent. Obstruction of two or three main hepatic veins produces two types of hemodynamic change: increased sinusoidal blood pressure and reduced sinusoidal blood flow.
Raised sinusoidal pressure is responsible for the liver enlargement, pain, and ascites via several mechanisms.
Sinusoidal dilation and congestion occur predominately in the central area of the hepatic lobules, where it is almost constant.

21. The filtration of interstitial fluid increases, which leads to passage of this fluid through the liver capsule when the capacity for hepatic lymph drainage is exceeded. Usually, the filtrated fluid has a high protein content because of the high permeability of the sinusoidal wall to proteins.
Portal pressure increases.

22. Changes in total hepatic blood flow
Indirect evidence suggests that in the microcirculation of the areas with impaired outflow, perfusion with portal blood decreases whereas perfusion with arterial blood increases.
Reperfusion injury may participate in the damage to liver cells.
Centrilobular necrosis is probably potentiated by congestion.

23. Within a few weeks after obstruction of the hepatic veins, fibrosis develops and can predominate either in the centrilobular area (when there is pure hepatic vein obstruction) or in the periportal area (when there is associated obstruction of the portal veins).
Within a few months, nodular regeneration may take place, predominantly in the periportal area. Cirrhosis can eventually develop but is found in only 10% to 20% of patients undergoing transplantation.

24. Doppler ultrasound images of Budd-Chiari syndrome
Doppler ultrasound images of Budd-Chiari syndrome. A, short stenosis of the left hepatic vein (arrow). B, Collateral circulation in the caudate lobe (arrow). C, Fibrous cord of the right hepatic vein (arrow). D, Venovenous circulation (arrow)

25. Although there is evidence that increased sinusoidal pressure is permanent state, decreased hepatic perfusion appears to be inconstant.
Natural mechanisms that are able to compensate for the decreased perfusion includes.
The development of venous collateral channels.
Redistribution of portal flow from areas where outflow is impaired toward areas where outflow is preserver.
Increased portal pressure.
Increased arterial flow.

26. Superimposed thrombosis of the intrahepatic portal veins appears to be common at an advanced stage, due to the combination of stagnant flow and an underlying thrombophilis state.
Obstruction of the extrahepatic portal vein is present in 10% to 20% of patients.
Areas where the portal and hepatic veins are simultaneously obstructed undergo infarction.
Depending on whether only the hepatic veins or both the hepatic veins and portal vein are obstructed, bridging fibrosis can be found.

27. Because obstruction of the hepatic veins is usually asynchronous, atrophy of the liver areas affected early may coexist with congestive or hyperplastic enlargement of the areas affected late. In 80% of cases, the caudate lobe is hypertrophied and thereby causes IVC stenosis.
Enlargement of the caudate lobe is due to its veins draining directly into the IVC caudal to the ostia of the main hepatic veins; the veins are preserved for a considerable time from the thrombotic process affecting the main hepatic veins.

28. Preservation of this drainage allows compensatory hypertrophy and also serves as an outflow for the intrahepatic venous collaterals.
Conversely, obstruction of these veins usually causes severe liver disease.

29. Focal nodular regenerative hyperplasia-like lesions in a liver with Budd-Chiari syndrome. A, T1-weighed magnetic resonance imaging (MRI) showing multiple hyperintense nodules (arrowhead). B, T2-weighed MRI showing that the nodules are hyperintense, some of them with a central scar (arrowhead); the inhomogeneous area of hyperintensity is congestive (arrow). C, Hepatic arteriography showing arterialization. The hepatic artery (arrow) is larger than the splenic artery, and there are multiple hypervascular areas. D, A sliced native liver at transplantation shows multiple nodules (arrow) in an otherwise congestive parenchyma. E, A fixed liver slice shows multiple pale nodules, some of them harboring a central scar (arrow). F, Low-power view of a nodule showing the central scar devoid of the portal vein (arrow); the neighboring liver parenchyma is congestive with two thrombosed hepatic veins

30. A frequent of long-standing BCS is the development of multiple large regenerative nodules.
These nodules due to focal loss of portal perfusion and hyperarterialization in areas with preserved hepatic venous outflow.
The cumulative incidence of HCC during follow-up was 4%.

31. Manifestations and course
Patients with BCS are 39 years old on average, and mostly females. The cardinal features of BCS are:
Ascites (80%), protein content higher than 3g/dl (or a serumascites albumin gradient >1.1 g/dl) is suggestive of BCS in the absence of cardiac or SOS.
Upper abdominal pain (60%).
Hepatic encephalopathy (10%).
Upper gastrointestinal bleeding.
Marked dilation of subcutaneous collaterals on the trunk is highly suggestive of vena cava obstruction.

32. Disease presentation
Acute: characterized by a short illness, abdominal pain and fever, ascites, marked elevation in serum aminotransferases, and markedly decreased coagulation factors.
Chronic: characterized by the indolent development of ascites or portal hypertensive bleeding with normal or mildly increased serum aminotransferases (less than five times the upper limit of normal values) and moderately decreased plasma coagulation factors; jaundice is uncommon.

33. Acute-on-chronic: is associated with a poorer outcome than is solely acute or chronic disease.
The clinical findings depends on the extent and on the speed of the obstructive process:
Obstruction of only one major hepatic vein usually develops without symptoms.
Slow obstruction of two or three major veins produces a chronic course but when accompanied by extensive collaterals, no symptoms at all.

34. Diagnosis
A diagnosis of BCS should be suspected when ascites, liver enlargement, and upper abdominal pain are simultaneously present or when intractable ascites contrasts with moderate alterations in liver function test results, when liver disease occurs in a patient with known risk factors for thrombosis, or when the liver disease remains unexplained after other common or uncommon causes have been excluded.

35. Hepatic venous outflow tract imaging
Diagnosis by: ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI).
Liver biopsy is indicated only in patients in whom the large hepatic veins and IVC are shown to be clearly patent on all imaging procedures.
Ultrasonography must combine color Doppler imaging and has become the first choice for the noninvasive diagnosis of BCS.

36. Diagnostic features
A large hepatic vein appearing to be void of flow signal or with reversed or turbulent flow.
large intrahepatic or subcapsular collaterals with continuous flow connecting the hepatic veins or the diaphragmatic or intercostal veins.
A spiderweb appearance, usually located in the vicinity of the hepatic vein ostia, together with the absence of a normal hepatic vein in the area.
An absent or flat hepatic vein waveform without fluttering.
A hyperechoic cord replacing a normal vein.

37. Absence of visualization or tortuosity of the hepatic veins on gray-scale real-time sonography, albeit with the presence of flow signals on Doppler imaging, is common but not specific in that it is also observed in patients with advanced cirrhosis of other origin.
A distinctive feature, however, is the association with intrahepatic or subcapsular venous collaterals. This collateral circulation is the most sensitive feature for the diagnosis of BCS because it is found in more than 80% of patients.

38. MRI with intravenous gadolinium enhancement allows visualization of the obstructed hepatic veins and IVC, intrahepatic of subcapsular collaterals, and the spiderweb pattern. MRI, however, is not as effective as sonography in demonstrating the intrahepatic collaterals.
On CT a striplike appearance or failure to visualize the hepatic veins suggests hepatic vein obstruction.
However, false-positive and indeterminate results occur in approximately 50% of patients.

39. Venography is recommended when the diagnosis remains uncertain after the previously described imaging procedures or during a therapeutic procedure.
Three patterns of opacification are regarded as specific during retrograde catheterization
A fine spiderweb network pattern spreading out from the catheter tip wedged into a blocked vein without filling of venous radicals.

40. When there is incomplete occlusion of the hepatic veins, a coarse network of collateral veins that arch autward from the catheter tip and then come together again near the site of entry of the hepatic vein into the IVC.
A patent vein upstream from a hepatic vein ostia and a distorted appearance of the hepatic veins. Direct percutaneous venography can show a localized obstruction in the vicinity of the ostia when the hepatic veins cannot be entered via retrograde cannuloation.

41. Computed tomographic images of Budd-Chiari syndrome
Computed tomographic images of Budd-Chiari syndrome. A, Hepatic veins and paravertebral collaterals (arrows). B, In the same patient 2 months later, thrombosis of the vein collaterals and the inferior vena cava (arrow) is apparent. Compensatory paravertebral circulation has developed, and ascites is visible. V, Diffuse distal hepatic vein thrombosis (arrow). D, Venovenous collateral circulatin (arrow)

42. Simultaneous hepatic and caval vein obstruction
Simultaneous hepatic and caval vein obstruction. A, Venography showing the hepatic vein and cavocaval collaterals (arrow). B, Venousphase computed tomography showing obstruction of the inferior vena cava (arrow) associated with thrombosis of the hepatic vein stump

43. Spiderweb on venography

44. Diagnostic features
Particular features can be highly suggestive of BCS. An enlarged caudate lobe is found in about 80% of patients. This hypertrophy is explained by preservation of the multiple hepatic veins draining this lobe directly into the IVC.
However, caudate lobe enlargement is also common in many cases of cirrhosis of other origin. Visibility and dilation (> 3 mm in diameter) of the hepatic caudate veins on MRI or Doppler ultrasound may help differentiate BCS from cirrhosis.

45. An altered parenchymal perfusion pattern is seen on CT or MRI after bolus intravenous injection of contrast material.
The most characteristic pattern is early homogeneous central enhancement (particularly at the level of the caudate lobe), together with delayed patchy enhancement and prolonged retention of contrast medium in the periphery of the liver. This pattern is suggestive but neither sensitive nor specific, as it is observed in many other situations in which portal venous perfusion is compromised. Among the latter conditions, constrictive pericarditis.

46. Large regenerative hypervascular nodules are frequently seen in patients with BCS.
They are usually multiple, with a typical diameter of 0.5 to 3 cm.
On multipasic helical CT, hyperattenuating on arterial phase images and remain slightly hyperattenuating on portal venous phase images.
In view of the risk for bleeding in patients who are likely to receive anticoagulation or thrombolytic therapy, liver biopsy should be performed for a diagnosis of BCS only when an obstructed hepatic venous outflow tract has not been demonstrated on noninvasive imaging. Liver.

47. Treatment Treatment of the cause
Screening for all possible causes and risk factors present to identify conditions that require a specific therapy:
Immunosuppressive therapy for behçet disease.
Hematopoietic stem cell transplantation for PNH.
Oral contraceptive use should generally be stopped.
In patients with known BCS that is well controlled, pregnancy should not be contraindicated because maternal outcome and fetal outcome beyond the 20th week of gestation are good.

48. A) Anticoagulation therapy
According to recent recommendations:
Anticoagulation therapy with low-molecular- weight heparin should be initiated immediately, with a target anti-xa activity of 0.5 to 0.8 IU/ml, and be changed to an oral anticoagulation agent when clinically appropriate, with an INR target of between 2 and 3.
anticoagulation therapy should be used long-term unless a major contraindication is present or a complication of anticoagulation therapyoccurs.

49. These recommendations have been based on the following circumstantial evidence:
an improved outcome since the introduction of systematic anticoagulation.
Reports of recanalization of thrombosed hepatic veins.
Efficacy of anticoagulation for recanalization of recent thrombosis of the portal vein or other deep veins.
reports of recurrent occlusion of the hepatic veins following angioplasty in patients not receiving anticoagulation

50. B) Pharmacologic and endoscopic treatment of portal hypertension
C) Recanalization of the hepatic venous outflow tract by thrombolysis, angiplasty, or stenting
1) Pharmacologic thrombolysis
By local or systemic administration has been performed in patients with BCS.
Local administration appears to cause more efficacious than systemic administration.
Thrombolysis is more effective when: thrombus is relatively recent (hours to weeks), with angioplasty of a stenosis, and with local infusion.

51. IVC obstruction are good candidates for thrombolysis
IVC obstruction are good candidates for thrombolysis. Thrombolysis exposes patients to risk for hemorrhage pulmonary embolism, and stroke.
2) Percutaneous angioplasty with stenting
Recanalization have been made via the IVC or by combining a transhepatic transvenous rendezvous approach for longer stenoses.
Combined angioplasty and stenting could be done.

52. Results
Recanalization in 80% to 90% of patients, but reocclusion occurs frequently.
Repeated assessment of patency and, when necessary, dilation improve secondary patency rates. Anticoagulation appears to be helpful in preventing complete reocclusion.

53. Complications
Are rare with the transvenous approach but more frequent with the transhepatic rendezvous technique.
Mortality seems to be low and not related to the procedure.

54. 3) Porto systemic shunting for liver decompression
Surgical
Mesocaval shunting with autologous jugular or prosthetic grafts and side-to-side portocaval shunting.
IVC obstruction precludes the use of these surgical shunts.
A mesoatrial shunt or cavoatrial shunt followed by side-to-side portocaval shunts or IVC stenting has been proposed in this situation. The overall mortality rate has been 25% to 30%.

55. TIPS
The 1- and 5- year liver transplantation-free survival rates of 88% and 78%, respectively.
Factors associated with a poor prognosis were suggested to be age, high bilirubin, and high INR. Patients with latter characteristics might benefit from directly undergoing liver transplantation.

56. Transcaval transjugular intrahepatic portosystemic (TIPS) for Budd-Chiari syndrome. A, transcaval portal vein cannulation. B, balloon dilation of the portovenous tract. C, expansion of the stent. D, Doppler ultrasound control of TIPS patency

57. 4) Liver transplantation
The overall actuarial survival rate was 76% at 1 year 71% at 5 years, and 68% at 10 years.
Most of the patients died within the first 3 months because of infection, multiorgan failure, graft failure, or hepatic artery thrombosis.
Renal failure, high bilirubin, and a previous surgical shunt or TIPS were associated with poor survival.

58. Treatment algorithm
Therapies that should be successively implemented include the following:
Anticoagulation, treatment of the underlying condition, and symptomatic treatment of the complications of portal hypertension in all patients with complications or portal hypertension in all patients with primary BCS.

59. Angioplasty/Stenting of short venous stenoses in symptomatic patients.
TIPS placement in patients not suited for or unresponsive to angioplasty/stenting.
Liver transplantation in patients unresponsive to TIPS or with fulminant hepatic failure.

60. Using this strategy the overall 5-year survival approaching 90%
Prognosis
Using this strategy the overall 5-year survival approaching 90%

61. Sinusoidal Obstruction Syndrome / Venoocclusive
Disease
SOS (previously called venoocclusive disease [VOD]) is characterized by nonthrombotic obstruction of the sinusoids, which may extend to the central veins, in the absence of thrombosis or other underlying disorder of the hepatic veins.
The initial lesion is a toxic injury to the sinusoids. Because central vein lesions are not required for recognition of the syndrome, the name has been changed from VOD to SOS.

62. Sinusoidal Obstruction Syndrome / Venoocclusive
Pathogenesis
Sinusoidal cells are more sensitive to drug or toxin injury than hepatocytes are.
In animal model with SOS, sinusoidal cells round up, and red cells penetrate into the space of Disse and dissect the sinusoidal lining.
Kupffer cells, sinusoidal cells, and stellate cells will then embolize downstream and obstruct sinusoidal flow.

63. Depletion of glutathione by drugs or toxins, increased metalloproteinase activity, and depletion of nitric oxide (NO) play important roles in inducing experimental SOS/VOD.
Bone marrow-derived progenitors replaced sinusoidal endothelial cells after injury, which suggested that toxicity to bone marrow progenitors impairs repair whereas timely infusion of bone marrow has therapeutic benefit.
Thus SOS/VOD might not be just a liver disease but a combined liver-bone marrow disease.

64. 1) Pyrrolizidine Alkaloid-Containing Plants
Causes
1) Pyrrolizidine Alkaloid-Containing Plants
It has been estimated that 3% of the flowering plants in the world contain pyrrolizidine alkaloids, as Senecio, Crotalaria, Heliotropium, and Symphytum .
The alkaloids are metabolized to toxic pyrrole metabolites.

65. 2) Chemotherapeutic agents myeloablative regimens before hematopoietic stem cell transplantation
The incidence ranges from 20% to 50%, with regimens including cyclophosphamide in combination with either busulfan, total-body irradiation, BCNU, carboplatin, or cytarabine.
Finally, avoiding these regimens cyclophosphamide regimens, excluding patients with chronic hepatitis, and using lower doses of radiation have contributed to reducing the incidence of SOS/VOD after stem cell transplantation.

66. 3) Other agents in the absence of stem cell transplantation
Agents such as gemtuzumab ozogamicin, 6-thioguanine, urethane 6-mercaptopurine, actinomycin D, dacarbazine, and azathioprine prine have been implicated.
Oxaliplatin, for colorectal liver metastases or pancreatic cancer.

67. Azathioprine and tacrolimus have both been implicated Following lung, kidney, and liver transplantation.
The incidence after OLT was 2%.
SOS/VOD was associated with a high incidence of acute rejection, thus suggesting an immunologic role.
SOS/VOD has developed in patients with Crohn disease or APLS who were treated with azathioprine.

68. 5) Alterations in Coagulation
4) Radiotherapy
SOS/VOD is seen in patients receiving 30 to 35 Gy.
5) Alterations in Coagulation
An altered intrahepatic coagulation cascade secondary to sinusoidal endothelial cell damage has been suspected in patients with SOS/VOD.

69. Manifestations and course Clinical and laboratory features
Clinical features in patients vary from an asymptomatic condition diagnosed on liver biopsy to severe disease leading to multiorgan failure with a mortality rate of 84%.
Symptoms include weight gain, ascites, right apper quadrant pain, hepatomegaly, and jaundice.

70. Grades of severity
Mild SOS/VOD Symptoms do not require specific treatment and the spontaneous course is favorable.
Moderate SOS/VOD, require treatment (mainly diuretics or water balance) but resolve with treatment.
Severe SOS, in which the symptoms require treatment but do not resolve before death or by day 100.

71. Clinical Criteria for the Diagnosis of sinusoidal obstruction syndrome after hematopoietic Cell Transplantation
EATTLE CRITERIA
Baltimore criteria
2 of 3 findings within 20 days of transplantation:
Hyperbilirubinemia plus ≥ 2 other criteria:
Bilirbin > 34.2 μmol/L (2 mg/dl)
Bilirubin 34.2 > μmol/L (2 mg/dl)
Hepatomegaly or right upper quadrant pain of liver origin
Hepatomegaly, usually painful
> 2% weight gain attributable to fluid accumulation
≥ 5% weight gain
Ascites

72. Imaging
Doppler ultrasound, MRI, and CT give no specific information for diagnosing SOS/VOD.
The presence of splenomegaly, umbilical vein recanalization, gallbladder wall thickening, enlarged portal vein, slow or reversed portal flow, and increased resistive artery index were somewhat specific but late indicators of SOS/VOD.
On contrast- enhanced CT or MRI, periportal edema is visible and the gallbladder wall is seen to be hyperattenuated.

73. Liver Biopsy
When clinical and imaging information are not sufficient a liver biopsy is recommended.
As early as 6 days after myeloabiative therapy, the subendothelial zone is widened and edematous and contains fragmented red cells, the sinusoids are enlarged and congestive, red cells extravasate through the space of Disse, and perivenular hepatocyte necrosis occurs.

74. Liver Biopsy
Next, stellate cells are activated, and fibrosis of the sinusoids and venules increases.
Later stages of fatal SOS are characterized by extensive collagenization of the sinusoids and venules. In clinically severe SOS/VOD hepatocyte necrosis and sinusoidal fibrosis, occlusion of hepatic venules .

75. Histology of sinusoidal obstruction syndrome/venoocdusive disease
Histology of sinusoidal obstruction syndrome/venoocdusive disease. A central vein is at the center of each panel. There is mar® thickening of its wall with fibrosis and edema. Hepatocytes and sinusoidal endothelial cells have disappeared in the centrilobuiar area. The sinusoid are destroyed and congestion is apparent. Upper left panel, hematoxylin and eosin stain; lower left panel, reticulin stain; right panels, Masstij| trichrome stain

76. Course and Prognosis
Predictors of a poor outcome are high serum ALT levels, high hepatic venous pressure gradient, portal vein thrombosis, and multiorgan failure.

77. Prophylaxis
Adapting the conditioning for patients with high-risk factors
High risk patients should be identified before initiating myeloablative regimens.

78. Markers of high risk are
Preexisting extensive hepatic fibrosis, viral hepatitis, myelofibrosis with extramedullar hematopoiesis, nonalcoholic or alcoholic hepatitis, recent treatment with gemtuzumab, ozogamicin, or a previous history of S VOD.
Regimens that are less liver toxic should be adopted including: reduced-intensity regimens, regimens without cyclophosphamide, and regimens with lower doses of total-body irradiation <12 Gy.

79. Medical Prophylaxis A) Defibrotide B) Throtnbomodulin
Is a single-stranded polydeoxyribonucleotide that has specific binding sites on vascular endothelium, Defibrotide up-regulates the release of prostaglandin E.
B) Throtnbomodulin
No, and tissue plasminogen activator and decreases thrombin generation, tissue factor expression, PAI-1, and endothelin activity.

80. Treatment of established sinusoidal instruction syndrome
Prostaglandin E1 reduced the overall incidence of SOS/VOD in one study, but no impact was shown on fatal SOS/VOD.
In conclusion, no benefit in the prevention of fatal SOS/VAD has thus far been shown, so no recommendation can be made for their use.
Treatment of established sinusoidal instruction syndrome
In addition to nonspecific therapy for fluid retention, sepsis, and renal, respiratory, and circulatory failure, various specific treatments have been proposed once SOS/VOD is established.

81. 1) Thrombolysis 2) Defibrotide
There is a risk for severe bleeding, in these patients, Therefore thrombolysis is not recommended.
2) Defibrotide
The AASLD practice guidelines did not recommend using defibrotide as long as randomized controlled trials have not demonstrated efficacy.

82. 3) Transjugular Intrahepatic Portosystemic Shunt
The AASLD practice guidelines did not recommend using defibrotide as long as randomized controlled trials have not demonstrated efficacy.

83. 4) Liver transplantation
There are reports of successful OLT in patients with SOS/VOD.
Based on these limited data, it has been proposed that patients who undergo hematopoietic stem cell transplantation for a benign condition or in whom the underlying malignancy has a favorable prognosis after transplantation may be considered for OLT when severe SOS / VOD develops

84. Thank You