Anicteric Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation in Children

Introduction

Hepatic veno-occlusive disease (VOD) is a potentially fatal complication after hematopoietic stem cell transplantation (HSCT).  The Baltimore [1] and the Seattle criteria [2]. Some patients with VOD may not have hyperbilirubinemia, remain anicteric, and still progress to have severe VOD.  The intent of our study is to evaluate the clinical course and outcomes of patients with anicteric VOD compared to those with hyperbilirubinemia. 

Methods

A retrospective review of all patients diagnosed with VOD while undergoing HSCT at Nationwide Children’s Hospital from 1992 until June, 2014 was done. Both Seattle and Baltimore criteria were applied to each patient. Supportive care treatment with level of care (LOC) was defined as: Level 1: General floor level management (i.e. diuretics, pain control, etc.), Level 2: ICU level support for < 2 body systems (i.e. mechanical ventilation (MV) for respiratory failure, vasopressors (VP) for heart failure etc.) and Level 3: ICU level support > 3 body systems (i.e. MV + VP + Dialysis, etc.).  Standard statistical methods were used for analysis.

Results

30 patients were diagnosed with VOD over the last 22 years, 9 (30%) were anicteric, 20 (67%) icteric and one with undocumented bilirubin level was excluded from all further analysis. There was no difference in the characteristics of the two groups in regards to percentage weight gain, hepatomegaly, abdominal pain, demonstration of portal venous flow reversal, or outcome. The total duration of treatment and level of supportive care given was significantly higher in patients with icterus than without (P = 0.224) and P= 0.0081) respectively. Total days for disease resolution in patients with icterus was 32 days compared to 16 days for those without (p=0.022). Nine of the patients with icterus received specific treatment compared to only one in the anicteric group. Seven cases were diagnosed with VOD by the Seattle criteria at a median of day +15 post HSCT, but treatment was delayed  by 1-11 days for lack of hyperbilirubinemia, 2 of these never developed hyperbilirubinemia; 4 of 7 cases died. Overall 2 with anicteric and 12 cases with icteric VOD died.

Discussion

The Baltimore criteria appear to be more stringent and cases with anicteric VOD do not meet these diagnostic criteria. This retrospective study describes the features of anicteric VOD at a single center. Even if the patients met the Seattle criteria, treatment was delayed for lack of hyperbilirubinemia or flow reversal on hepatic ultrasound, neither of which are required criteria. Patients with anicteric VOD had a better outcome than those with hyperbilirubinemia, but our study shows that there can be significant morbidity and even mortality associated with anicteric VOD. There seems to be a poor understanding and awareness of anicteric VOD as a diagnosis. Earlier disease recognition could lead to more prompt and aggressive treatment leading to improved outcomes.