What Is Sinusoidal Obstruction Syndrome?
The liver is the largest complex vital organ of the human body. The obstruction in the small veins of the liver is called obstruction syndrome. A sinusoidal obstructive syndrome is an immunodeficiency disease, a rare complication of stem cell transplantation. It happens due to chemotherapy and bone marrow transplantation and can present in acute, subacute, and chronic forms.
What Leads to Sinusoidal Obstruction Syndrome?
Sinusoidal obstruction syndrome typically starts within 10 to 20 days after transplantation. From chemotherapy sessions, it can arise as soon as 3 to 6 weeks after starting the therapy. Acute sinusoidal syndrome it presents within 1 to 3 weeks of exposure to the medication, while chronic, takes weeks, months, to years from the start of the condition. Due to toxic liver injury, the sinusoidal cells of the liver cause sloughing of the endothelial layer around and symbolizes hepatic venules, causing gradual fibrosis of the venules, resulting in hepatic congestion, the same as in Budd-Chiari syndrome and post-sinusoidal portal hypertension.
How Does the Mechanism of Injured Cells Lead to Sinusoidal Obstruction Syndrome?
Damage to the endothelial cells in the liver is followed by necrosis and extrusion into the sinusoids leading to congestion and obstruction. Stellate cells (star-shaped cells) become activated and produce collagen and extracellular matrix. Hepatocellular necrosis occurs due to the loss of endothelial cells. Irradiation of the liver with antineoplastic agents causes this syndrome.
What Are the Signs and Symptoms of Sinusoidal Obstruction Syndrome?
The signs and symptoms of this condition are:
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Rapid weight gain.
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Fatigue.
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Malaise.
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Muscle weakness.
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Hepatic encephalopathy (a neurological disorder caused by liver disease).
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Right upper quadrant pain.
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Hyperbilirubinemia (increase in levels of bilirubin in the blood).
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Abnormal liver function.
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Acute renal failure.
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Painful hepatomegaly (swelling of the liver).
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Jaundice (yellowish discoloration of mucous membrane, skin, and whites of the eye).
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Ascites (fluid-filled in the abdominal cavity).
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Unexplained thrombocytopenia (deficiency of platelets in the blood).
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Abdominal bloating.
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Serum enzyme elevations.
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Portal hypertension.
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Clinical presentation of cirrhosis.
What Are the Agents That Cause Sinusoidal Obstruction Syndrome?
Agents that cause sinusoidal obstruction syndrome include:
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Chemotherapeutic agents like alkylating agents, such as Busulfan, Cyclophosphamide, Melphalan, Carmustine (BCNU), Dacarbazine, and Thiotepa.
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Platinum coordination complexes - Carboplatin, Cisplatin, Oxaliplatin.
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The thiopurines like Mercaptopurine, Azathioprine, and Thioguanine.
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The pyrrolizidine alkaloids (found in many plants and shrubs) can also lead to this syndrome.
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Exposure linked with bush tea, contaminated rice, and wheat food sources with pyrrolizidine-containing plants and weeds.
How Is the Diagnosis Made for Sinusoidal Obstruction Syndrome?
After successful hematopoietic cell transplantation or cancer chemotherapy, the obstruction syndrome can be diagnosed based on the clinical signs and symptoms. Clinical interpretation of sinusoidal obstruction syndrome is mainly based on the criteria of liver injury within 20 days of bone marrow transplantation:
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Sudden weight gain (bodyweight >2 %).
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Hepatomegaly and pain in the liver.
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Increase in the levels of serum bilirubin.
Some blood investigations aid in the diagnosis, like bilirubin levels in the blood.
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Liver Histology- It is a viable approach because of thrombocytopenia and neutropenia after myeloablation or chemotherapy.
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Transjugular Liver Biopsy- It is the most reliable means of diagnosis and grading severity. Concurrent measurement of hepatic venous pressure.
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Ultrasound- To diagnose changes in liver texture due to congestion, ascites, and hepatomegaly. This may also reveal portal vein dilation, venous pulsatility, hepatofugal portal venous flow, and gallbladder wall thickening.
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CT (Computed Tomography) Scan- This scan can reveal hepatomegaly, ascites, portal vein dilation, and nutmeg liver.
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MRI (Magnetic Resonance Imaging)- MRI along with hepatocyte-specific agent shows a diffuse hypointense reticular pattern and T1 delayed hepatobiliary phase.
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Doppler Ultrasound-It helps in the diagnosis of portal hypertension, impedance to hepatic artery blood flow. Measurement of the hepatic venous gradient can assist in predictive value also.
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Hepatic Elastography- It is an invasive imaging technique to give accurate monitoring of treatment response.
What Is the Treatment Given for Sinusoidal Obstructive Syndrome?
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The primary treatment element includes managing complications like electrolyte, acid and base imbalance, hypotension, renal and pulmonary failure, and infections.
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If venous thrombosis is present, anticoagulants are given.
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In acute liver failure cases, infusions of N-acetyl cysteine to replenish glutathione levels are beneficial.
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Defibrotide (a mixture of oligodeoxyribonucleotides with antithrombotic and pro fibrinolytics) can be beneficial.
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Liver transplantation is rarely recommended in severe cases of advanced malignancy and myeloablation.
What Preventive Measures Can Be Taken to Avoid Sinusoidal Obstruction Syndrome?
The preventive measures for this condition are likely effective after applying therapies when the liver injury has occurred. The use of chemotherapies and conditioning regimes with lower rates can be helpful to patients with a high risk of pre-existing liver conditions. Replacing glutathione with N-acetyl cysteine is an excellent approach after cytotoxic therapy and myeloablation, but this decreases the efficiency of chemotherapy. Use of less aggressive myeloablative regimens, monitoring of drug levels, appropriate use of pharmacokinetics information, decreased level of bone marrow recipients in chronic hepatitis C cases, screening of donor blood for anti- HCV, and decrease in post-transfusion hepatitis C. All the above methods can reduce the intensity and prevent the condition.
What Is the Differential Diagnosis of Sinusoidal Obstruction Syndrome?
The differential diagnosis of this condition are:
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Sepsis (infective damage to one's own tissues is a life-threatening condition).
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Graft versus host defense.
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Drug-induced liver injury (liver inflammation due to exposure to certain drugs).
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Viral hepatitis (inflammation of the liver due to viral infection).
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Herpes simplex.
What Is the Prognosis of Sinusoidal Obstruction Syndrome?
The risk of death is about 10 % in mild diseases and ranges up to 20 % in moderate cases. It can be greater than 80 % when associated with bone marrow transplantation and multiorgan failure.
Conclusion:
After a hematopoietic cell transplant, sinusoidal obstructive syndrome is a rare but devastating condition. Mild conditions do not require medical attention; for patients with moderate conditions, fluid management with a concentration on intravascular volume is done to maintain kidney perfusion. The ascitic fluid is removed judiciously to control pain in the abdomen and discomfort with breathing. Prompt treatment is necessary in severe cases, and preventive measures should be implemented to avoid high risks. Though the complication of this condition is devastating and life-threatening, the significantly affected individuals improve with the proper medical intervention.
