P2863 - Atypical Presentation of Late-Onset Hepatic Sinusoidal Obstruction Syndrome

Shea Nagle, MD, MPH, Steven Park, MD, Edwin Lee, MD, Charlotte Ryan, MD, Maisa Abdalla, MD, MPH
University of Rochester Medical Center, Strong Memorial Hospital, Rochester, NY

Introduction: Hepatic Sinusoidal Obstruction Syndrome (Veno-Occlusive Disease) is a rare life-threatening complication of hematopoietic stem cell transplant (HSCT) caused by damage to sinusoidal endothelial cells. SOS most commonly occurs within 21 days of HSCT and has a high mortality. Early identification of high-risk patients with severe disease is of utmost importance and clinicians should be aware of risk factors and management.

Case Description/Methods: A 58 year-old female with history of NASH and myelodysplastic syndrome s/p pre-conditioning with busulfan/fludarabine and allogenic HSCT (CMV serostatus +/+) complicated by graft-versus-host disease (GVHD) involving the skin (biopsy confirmed) and liver (no biopsy confirmation) presented D75 post-HSCT with weight gain and anasarca. Physical exam was notable for ascites and lower extremity pitting edema without jaundice, abdominal tenderness or organomegaly. Patient’s medications included prednisone and tacrolimus.

Laboratory work-up revealed ALT 31[0-35U/L], AST 25[0-35U/L], Alk Phos 111[35-105U/L], T.Bili 0.5[0-1.2mg/dL], Creatinine 1.29[0.51-0.95mg/dL] and Albumin 3.1[3.5-5.2g/dL]. CMV PCR was undetectable, Tacrolimus level 8.9ng/mL, Ferritin 111[10-120ng/mL], SMA 12[0-19U], and AMA 2.0[0-24.9U]. Patient was HAV immune, non-HBV immune without active Hepatitis B and negative for HCV antibody. Diagnostic paracentesis revealed albumin < 1.0 g/dL, protein 1.7 g/dL and 15 nucleated cells. SAAG was >1.1. A transjugular liver biopsy with pressure measurements revealed HVPG of 14mmHg and pathology findings of acute venous outflow obstruction with central hemorrhage and fibrotic terminal hepatic venules (Figure 1). Patient was started on defibrotide infusion.

Discussion: SOS is a life threatening complication of HSCT occurring classically within 21 days of transplant with a high mortality rate (80%) in severe cases. Damage to the sinusoidal epithelium causes portal hypertension. Risk factors include pre-transplant factors, transplant factors, and medications. Defibrotide is the only FDA-approved treatment for SOS. Our case highlights a difficult diagnosis of late-onset (D75 post-HSCT) SOS given concurrent history of NASH and GVHD, ultimately diagnosed with a liver biopsy. Our patient lacked some common signs and symptoms, such as painful hepatomegaly, hyperbilirubinemia, and ascites with high total protein which make up the diagnostic criteria (Table 1). Understanding the risk factors and clinical manifestations can assist in diagnosis and management.


Figure: Figure 1. Sinusoidal Obstructive Syndrome (Veno-Occlusive Disease). A. Early stage with pronounced centrilobular congestion and sinusoidal dilatation consistent with acute venous outflow obstruction (normal portal tract lower right). B. With progression, the central veins become completely obliterated by fibrous tissue.
Table 1. Criteria for SOS diagnosis, adapted from European Society for Blood and Marrow Transplantation revised diagnostic criteria for classical and late-onset hepatic SOS.

Classical SOS Diagnostic Criteria	Late Onset SOS Diagnostic Criteria
≤ D21 s/p HSCT	> D21 s/p HSCT
Bilirubin ≥ 2mg/dL + Two (2) of the following	Classical SOS Symptoms > D21
Painful hepatomegaly	OR
Weight gain > 5%	Ultrasound evidence of SOS + Two (2) or more of the following
Ascites	Bilirubin ≥ 2mg/dL
	Painful hepatomegaly
	Weight gain > 5%
	Ascites
	OR
	Histological evidence of SOS

Disclosures:
Shea Nagle indicated no relevant financial relationships.
Steven Park indicated no relevant financial relationships.
Edwin Lee indicated no relevant financial relationships.
Charlotte Ryan indicated no relevant financial relationships.
Maisa Abdalla indicated no relevant financial relationships.


Shea Nagle, MD, MPH, Steven Park, MD, Edwin Lee, MD, Charlotte Ryan, MD, Maisa Abdalla, MD, MPH. P2863 - Atypical Presentation of Late-Onset Hepatic Sinusoidal Obstruction Syndrome, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.