Recognize Hepatic Sinusoidal Obstruction Syndrome in patients with cancer.
Hepatic sinusoidal obstruction syndrome (SOS), a serious complication that can occur following either allogeneic or autologous hematopoietic stem cell transplantation (HSCT), was described by Tracy Krimmel, MSN, AOCN[R], APRN-BC, and Loretta A. Williams, PhD, RN, in the January 2008 issue of the Oncology Nursing Forum. Hepatic SOS develops early in the transplantation process, usually by day 35, and, in its severe form, can have a mortality rate as high as 67%. The incidence of hepatic SOS can be as high as 70%, depending on factors such as the conditioning regimen used and hepatic function prior to transplantation.
Although the pathogenesis of hepatic SOS is not understood, it is thought to begin with injury to the hepatic venules. The vascular inflammatory process leads to deposits of fibrin in the portal vessels, causing obstruction. The sinusoids become dilated and hepatocytes become necrotic when collagen accumulates in the sinusoids and venules. Injury to the sinusoidal endothelial cells and the hepatocytes in zone 3 of the liver, located around the central veins, is an important initial event in hepatic SOS. Hepatocytes in zone 3 contain high concentrations of cytochrome P450, an enzyme that metabolizes many chemotherapeutic agents, including busulfan (Myleran[R], GlaxoSmithKline) and metabolites of cyclophosphamide. Inability to effectively metabolize those chemotherapeutic agents increases liver damage. These events lead to widespread disruption of liver function.
Cytotoxic agents implicated in the development of hepatic SOS include busulfan, a common conditioning agent used in HSCT, and gemtuzumab ozogamycin (Mylotarg[R], Wyeth Pharmaceuticals), an anti-CD33 monoclonal antibody. Risk factors for hepatic SOS include
* Karnofsky score less than 90%
* Age older than 20 years
* History of liver disease
* Intensive conditioning regimen
* Fungal infection
* Elevated aspirate aminotransferase at the start of HSCT
* Previous abdominal radiation
* Female gender
* Advanced malignancy
* Prior exposure to amphotericin B
* Total number of days on broad-spectrum antibiotics
* Total number of days with fever before HSCT.
Having an unrelated donor and advanced-stage malignancy also are substantial risk factors for hepatic SOS in pediatric patients.
Symptoms and Diagnosis
Clinical symptoms of hepatic SOS include unexplained weight gain, painful hepatomegaly, and jaundice. Diagnostic criteria include jaundice (total bilirubin > 2.0 mg/dl) and at least two of the following.
* A gain of more than 5% of the patient's total body weight
Hepatic SOS is difficult to diagnose because of the many causes of hepatic toxicity in patients undergoing HSCT and because the diagnostic criteria overlap with many other complications that can occur following HSCT.
Because of the danger of bleeding or infection from invasive procedures during HSCT, diagnosis of hepatic SOS often is made clinically based on the classic signs of weight gain, painful hepatomegaly, hyperbilirubinemia, and ascites. Transfemoral or transjugular liver biopsy and wedged hepatic venous pressure gradient measurement are the preferred methods of pathologic diagnosis of hepatic SOS. Percutaneous liver biopsy is not recommended. Doppler ultrasound of the liver, computed tomography of the abdomen, magnetic resonance imaging of the liver, and a hepatitis panel can assist in the clinical diagnosis.
No definitive treatment exists for hepatic SOS, and recommendations center around supportive care measures. Approximately 70% of cases of hepatic SOS following HSCT will resolve spontaneously with supportive care.
* Maintain adequate intake and output.
* Adjust medication doses if hepatic and renal impairment is present.
* Protect the patient's kidney function.
Defibrotide has been studied in the prevention and treatment of hepatic SOS. For recommendations, refer to Krimmel and Williams (2008).
Nursing assessments should include monitoring mental status changes to detect the development of hepatic encephalopathy, daily measurement of abdominal girth for ascites, and daily weight measurement to assess fluid retention. Supportive care should continue until the hepatic SOS resolves and liver cells regenerate.
Krimmel, T., & Williams, L.A. (2008). Hepatic sinusoidal obstruction syndrome following hematopoeitic stem cell transplantation. Oncology Nursing Forum, 35(1), 3740.
RELATED ARTICLE: Key Definitions.
Conditioning regimen: provides immunosuppression to prevent rejection of the transplanted graft; traditionally achieved by delivering maximally tolerated doses of multiple chemotherapeutic agents with nonoverlapping toxicities, with or without radiation
Hematopoietic stem cell transplantation: IV infusion of autologous (self-donor) or allogeneic (non-self-donor) stem cells collected from bone marrow, peripheral blood, or umbilical cord blood to reestablish hematopoietic function in patients with damaged or defective bone marrow or immune systems
Hepatic sinusoidal obstruction syndrome: a toxic injury to sinusoidal endothelial cells causing a cascade of events, including compromised blood flow to centrilobular hepatocytes, fibrosis, and obstruction of hepatic blood flow; also known as veno-occlusive disease of the liver
Hepatocytes: functional cells of the liver that are supported by reticuloendothelial cells
Sinusoids: the vascular spaces that separate individual plates of hepatocytes; blood from the hepatic and portal veins combine in the sinusoids and drain into the central venules.
RELATED ARTICLE: Case Study.
J.M., a 43-year-old man with acute myelogenous leukemia with a monosomy 7 cytogenetic abnormality, received an allogeneic hematopoietic stem cell transplant (HSCT) from his human leukocyte antigen-matched brother. Past treatments included idarubicin and cytarabine induction therapy followed by a cycle of high-dose cytarabine. J.M. was in complete remission prior to the HSCT. The conditioning regimen for the HSCT was busulfan and cyclophosphamide. Eighteen days after his HSCT, J.M.'s total bilirubin rose from 1.0 mg/dl to 3.6 mg/dl within 24 hours. His alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were normal. J.M. complained of mild right upper-quadrant abdominal pain (3 on a 010 scale). J.M. had been gaining one to two pounds per day over the past few days, for a total of 10 pounds in the past week. He was slightly jaundiced. The transplantation team suspected that J.M. was developing hepatic sinusoidal obstruction syndrome (SOS).
What were J.M.'s risk factors for hepatic SOS? What were J.M.'s diagnostic signs of hepatic SOS? What are the most reasonable management options for J.M.'s hepatic SOS? Visit http://bloodmarrow.vc.ons.org/page/4917 to discuss the case with other readers.
"Five-Minute In-Service" is a monthly feature that offers readers a concise recap of a full-length article published in the Clinical Journal of Oncology Nursing or Oncology Nursing Forum (ONF). This edition summarizes "Hepatic Sinusoidal Obstruction Syndrome Following Hematopoeitic Stem Cell Transplantation" by Tracy Krimmel, MSN, AOCN[R], APRN-BC, and Loretta A. Williams, PhD, RN, which is featured in the January 2008 issue of ONF. Questions regarding the information presented in this Five-Minute In-Service should be directed to the ONF editor at ONFEditor@ons.org. Photocopying of this article for educational purposes and group discussion is permitted.