SUPERStudy: Hepatic Sinusoidal Obstruction Syndrome (HSOS)

By usmlevideoss

Introduction

Hepatic Sinusoidal Obstruction Syndrome (HSOS), formerly known as veno-occlusive disease (VOD), is a condition marked by obstruction of small hepatic veins and sinusoids. This leads to liver dysfunction, portal hypertension, and systemic complications. It often occurs after chemotherapy or hematopoietic stem cell transplantation (HSCT).

Etiology

  1. Primary Causes:
    • Chemotherapy/Radiotherapy: Particularly alkylating agents (e.g., cyclophosphamide, busulfan).
    • Hematopoietic Stem Cell Transplantation (HSCT): High-risk conditioning regimens.
    • Herbal Medications: Pyrrolizidine alkaloid-containing plants.
  2. Other Causes:
    • Liver irradiation.
    • Autoimmune diseases.
    • Hepatic infections.

Epidemiology

  • Incidence: 5–60% in HSCT recipients, depending on the conditioning regimen.
  • Risk Factors:
    • High-dose chemotherapy.
    • Preexisting liver disease.
    • Concurrent use of hepatotoxic drugs.
  • Population: More common in pediatric and immunocompromised patients.

Pathophysiology

  1. Endothelial Cell Injury:
    • Toxins or chemotherapeutic agents damage sinusoidal endothelial cells.
    • Endothelial injury causes detachment and narrowing of sinusoids, leading to thrombosis.
  2. Venous Outflow Obstruction:
    • Increased sinusoidal pressure causes hepatocellular injury, portal hypertension, and hepatic congestion.
  3. Hepatic Consequences:
    • Sinusoidal congestion, fibrosis, and hepatocellular necrosis.

Clinical Manifestations

  1. Early Symptoms (within 21 days of insult):
    • Right upper quadrant pain.
    • Hepatomegaly.
    • Jaundice.
    • Ascites.
  2. Severe Cases:
    • Rapid weight gain due to fluid retention.
    • Multi-organ failure (e.g., kidney and pulmonary involvement).
    • Hepatic encephalopathy.

Diagnosis

  1. Clinical Criteria (e.g., Seattle or Baltimore Criteria):
    • Weight gain >5% of baseline.
    • Hepatomegaly with right upper quadrant pain.
    • Elevated bilirubin (>2 mg/dL).
  2. Imaging:
    • Doppler Ultrasound: Reduced hepatic venous flow or reversal of portal flow.
    • CT/MRI: Evidence of hepatic congestion.
  3. Liver Biopsy:
    • Rarely performed due to bleeding risk.
    • Confirms sinusoidal congestion and fibrosis.

Treatment

  1. Supportive Care:
    • Fluid management.
    • Diuretics: For ascites control.
    • Pain management.
  2. Specific Therapies:
    • Defibrotide: Improves endothelial cell function; approved for severe HSOS.
    • Anticoagulation: Used in select cases.
  3. Preventive Strategies:
    • Reduced-intensity conditioning regimens.
    • Prophylactic defibrotide in high-risk patients.

Prognosis

  • Mild Cases: Often self-limiting with supportive care.
  • Severe Cases: Mortality >80% if untreated due to multi-organ failure.
  • Improved Outcomes:
    • Early diagnosis and treatment with defibrotide significantly improve survival.

SUPERPoint

Early recognition and treatment with defibrotide are critical to improving outcomes in hepatic sinusoidal obstruction syndrome.

SUPERFormula

Patient presents with right upper quadrant pain, jaundice, hepatomegaly, and ascites + recent history of hematopoietic stem cell transplantation + endothelial injury from toxins/chemotherapy + sinusoidal congestion and fibrosis + hepatic venous outflow obstruction + portal hypertension = Hepatic Sinusoidal Obstruction Syndrome (HSOS).

References

Rezvani AR, Negrin RS. Hematopoietic Stem Cell Transplantation. In: Kaushansky K, Prchal JT, Burns LJ, Lichtman MA, Levi M, Linch DC. eds.Williams Hematology, 10e. McGraw-Hill Education; 2021.

Mehta RS, Hosing C. Allogeneic Transplantation. In: Kantarjian HM, Wolff RA, Rieber AG. eds. The MD Anderson Manual of Medical Oncology, 4e. McGraw Hill Education; 2022.