Veno-occlusive Hepatic Disease Treatment & Management
- Author: James L Harper, MD; Chief Editor: Jennifer Reikes Willert, MD more...
No specific treatment modality for veno-occlusive disease (VOD) that could serve as a reference or criterion standard has been established. Studies on the use of many drugs to treat VOD are limited to case reports and small series.
The primary goal of treatment is to normalize the flow in the sinusoidal vessels and veins by controlling the vasculitis and fibrin deposition.
Low-dose tissue plasminogen activator (t-PA) has been used to increase fibrin degradation. However, it achieved responses in less than one third of patients [27, 28] A recent pediatric series reported on 12 children with veno-occlusive disease, including 5 with multiorgan failure who were treated with t-PA.  The survival rate in the 5 patients with severe veno-occlusive disease treated with t-PA was only 20%. t-PA may be associated with fatal hemorrhage, and its use is not recommended in the presence of multiorgan failure. [28, 30]
Additional approaches have included antithrombin III (ATIII) replacement and ATIII administered in combination with heparin/t-PA. Although the combination of ATIII and heparin/t-PA has become the most commonly administered treatment in the United States, as of August 2000, no large-scale studies of these treatment approaches and no head-to-head comparison studies have been conducted. Therefore, definitive treatment recommendations are not available.
Various other anticoagulant strategies have been tried, with mixed results.
Defibrotide is a single-stranded polydeoxyribonucleotide derived from porcine tissue that possesses antithrombotic, thrombolytic, anti-inflammatory, and anti-ischemic properties. [31, 32, 33]
- In March 2016, the FDA approved defibrotide (Defitelio) for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT). Approval was based on findings of a phase 3 trial (n = 102) which observed significant improvement in survival and complete response with defibrotide 6.25 mg IV q6h compared to 32 historical controls. Survival at Day+100 post-HSCT was 38.2% in the defibrotide group and 25% in the control group (estimated difference of 230%; 95.1% confidence interval [CI] 5.2%-40.8%; P=.0109, using a propensity-adjusted analysis based on 4 prognostic factors of survival). Observed Day+100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% in the controls (19% difference using similar methodology; 95.1% CI 3.5-34.6; P=.0160).
- In preclinical studies, defibrotide exerted a protective effect on injured microvasculature.[35, 36, 37, 38, 39]
- Encouraging responses were observed in early retrospective clinical trials of defibrotide, mostly in adult patients who fulfilled criteria for severe veno-occlusive disease based on the presence of multiorgan failure. The initial study by Richardson et al showed a resolution of severe veno-occlusive disease in 8 of 19 patients, with 6 of 8 surviving past day 100.
- In a similar high-risk population, a complete response was shown in 36% of study participants after a median duration of treatment with defibrotide for 18 days
- A single-arm cohort study and a prospective randomized trial that mostly consisted of adult patients with severe veno-occlusive disease showed efficacy of defibrotide in the treatment of patients with severe veno-occlusive disease.[41, 42]
- In a pediatric study, preemptive treatment with defibrotide within 24 hours of clinical diagnosis was associated with a significantly superior outcome
The availability of defibrotide is limited to clinical studies and compassionate use because it is currently not licensed by the US Food and Drug Administration. Supportive care currently remains the mainstay of treatment because of the paucity of established and effective treatment modalities. This care includes support of renal and pulmonary function, which are commonly compromised in patients with veno-occlusive disease.
General recommendations are as follows:
Minimize exposure to potential hepatotoxic (ie, cyclosporine) and nephrotoxic agents (ie, aminoglycosides).
Avoid the use of low-dose dopamine because experimental evidence suggests that it may divert splanchnic blood flow.
Judiciously manage the sodium and water balance.
Diuretic medication is indicated when symptoms associated with excess extravascular volume are observed.
Opiate analgesia should be copiously administered, if indicated (ie, right upper quadrant pain).
When ascites cause respiratory compromise, paracentesis is appropriate. However, it should be performed with caution, and careful attention should be paid to coagulation parameters.
Renal and pulmonary failure are managed with hemodialysis, ultrafiltration, and mechanical ventilation, as indicated.
Patients with severe veno-occlusive disease and multiorgan failure are at increased risk for infection. Thus, even though engraftment may have occurred, vigilance regarding infection is appropriate, and recognition that febrile responses may be blunted is important.
Total parenteral nutrition, almost always used during hematopoietic stem cell transplantation (HSCT), is a potential source of additional liver damage and should be modified according to the guidelines in consideration of the hepatic injury.
Coagulopathy should be corrected.
Patients usually require consultation with several specialists because they frequently develop other end-organ dysfunction and multiorgan failure. The following specialists may be consulted:
Critical care specialist
Infectious disease specialist
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