Veno-Occlusive Disease of the Liver in the Absence of Elevation in Bilirubin in Pediatric Patients after Hematopoietic Stem Cell Transplantation

Abstract

Veno-occlusive disease (VOD) of the liver is a well-described and significant complication of hematopoietic stem cell transplantation (HSCT), with limited successful therapeutic options in severe cases. Prompt diagnosis and initiation of treatment is crucial to restrict the extent of disease. However, a subset of patients may not meet all current diagnostic criteria at presentation, and waiting for these to be met may delay therapy. We retrospectively reviewed 794 HSCT patients treated at our institution between 2003 and 2013, identifying 17 (2.1%) who developed VOD. Of these, 5 (29%) were noted to have an absence of elevated bilirubin at the time of VOD diagnosis and reversal of portal venous flow on ultrasound. Median total and conjugated bilirubin at VOD diagnosis were 1.0 and 0.2 mg/dL, respectively. All 5 patients were subsequently diagnosed with multiorgan failure associated with VOD, including 1 with encephalopathy. Four were treated with intravenous high-dose methylprednisolone (500 mg/m2 per dose every 12 hours for 6 doses). One patient received defibrotide therapy in addition to steroids and another supportive care alone. VOD resolved in 4 of 5 patients, with median time to resolution of VOD, defined as recovery of all organ function and normalization of bilirubin and portal venous flow, of 8 days. Two patients died later from progressive primary disease and chronic graft-versus-host disease, respectively. We conclude that a high index of suspicion for VOD should be maintained in patients despite lack of bilirubin elevation in the presence of other diagnostic criteria such as hepatomegaly, abdominal pain, ascites, or weight gain. Early ultrasound evaluation in these patients may lead to more timely diagnosis and therapeutic interventions.

Anicteric veno-occlusive disease after hematopoietic stem cell transplantation in children

“…Our results are similar to the study by Myers et al 10 who reported five patients with anicteric VOD at diagnosis, two of those remained anicteric and one of these two died. 10 Our study reconfirms the importance of not overlooking a diagnosis of VOD simply due to lack of hyperbilirubinemia. Anicteric VOD is common in children after HSCT and carries a significant morbidity and even mortality.…”

“…Total serum bilirubin is often used as a marker for response to treatment with defibrotide, as discussed in studies by Ho et al 7 and Richardson et al 8 However some patients with VOD may not have hyperbilirubinemia but still have all the other features consistent with VOD. 9,10 In a recent study by Myers et al, 10 five patients had a bilirubin of ⩽ 2 mg/dL at the time of diagnosis of VOD and reversal of portal venous flow (PVF) by ultrasonography; two of these continued to have a bilirubin of o 2 mg/dL. 10 There have been few studies focusing specifically on anicteric VOD.…”

“…9,10 In a recent study by Myers et al, 10 five patients had a bilirubin of ⩽ 2 mg/dL at the time of diagnosis of VOD and reversal of portal venous flow (PVF) by ultrasonography; two of these continued to have a bilirubin of o 2 mg/dL. 10 There have been few studies focusing specifically on anicteric VOD. The primary aim of this study is to assess the clinical course and outcomes of patients with anicteric VOD after HSCT in children.…”

Late effects in children who underwent hematopoietic stem cell transplantation (review)

“…Печеночная РТПХ является сегодня наиболее распространенным осложнением, ведущим к остаточным проявлениям в виде поздних эффектов, которые проявляются как поствоспалительный склероз и изменения внутри-печеночных желчных протоков [59]. В случае разви-тия ВОБ у пациента на ранних этапах после ТГСК в поздней перспективе будут отмечаться гепатомега-лия и дисфункция органа.…”

“…В случае разви-тия ВОБ у пациента на ранних этапах после ТГСК в поздней перспективе будут отмечаться гепатомега-лия и дисфункция органа. К развитию ВОБ чаще всего приводит использование бусульфана, треосульфана, циклофосфамида и кармустина [59]. В определен-ных случаях у ряда пациентов может фиксироваться очаговая гиперплазия, связанная с ВОБ.…”