Effectiveness of Ursodeoxycholic Acid As Prophylactic Agent Against Hepatic Sinusoidal Obstruction Syndrome in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Treatment of Hematological Malignancies

Hepatic sinusoidal obstruction syndrome (SOS) is a major and potentially fatal complication of hematopoietic cell transplantation (HCT). In May 2008, a risk-adapted SOS prophylaxis guideline was implemented for patients undergoing allogeneic HCT in Singapore General Hospital. Patients were stratified into 3 risk categories according to conditioning regimen and risk factors including preexisting hepatitis/cirrhosis or hepatic dysfunction. Low risk patients did not receive routine prophylaxis, and patients at moderate or high risk received oral ursodeoxycholic acid 250 mg TDS starting before conditioning till D+21 of HCT.

This study aimed to evaluate the efficacy of ursodeoxycholic acid in preventing hepatic SOS in patients undergoing allogeneic HCT. In addition, additional risk factors associated with SOS were also identified.

A retrospective study of patients who underwent allogeneic HSCT between Jan 2005 and May 2012 was carried out where medical records were reviewed. Outcomes were compared between patients who received ursodeoxycholic acid as prophylaxis (from May 2008 to May 2012) against historical controls (from Jan 2005 to Apr 2008). The primary outcome was the incidence of SOS. Secondary outcomes included SOS-related mortality, and liver function post HCT.

A total of 202 patients were included with 129 patients in the study group and 73 historical controls. The incidence of SOS was 14% in the study group vs 23.3% in historical controls (p=0.121). In the moderate risk category, a statistically significant reduction of 12.7% in SOS occurrence was associated with routine prophylaxis (12.7% vs 25.4%, p=0.039). Among high risk patients, the incidence was 27.3% in the study group and 10% in controls, p=0.586. SOS-related mortality was comparable between the 2 groups. Elevation in liver function tests (including bilirubilin, ALT, AST, ALP, and GGT) post HCT was significantly lower in patients receiving ursodeoxycholic acid as prophylaxis. Prior HCT was identified as risk factor associated with SOS (OR, 9.082; 95% CI, 2.57 – 32.089; p=0.01).

The use of ursodeoxycholic acid as prophylaxis resulted in a significant reduction in SOS occurrence in patients at moderate risk for this complication. However, the high incidence of VOD among high risk patients underscores the need for more effective prophylactic strategies in this population.

No relevant conflicts of interest to declare.