Daily Versus Alternate Day Plasma Exchange in Wilson Disease With Acute Liver Failure in Children

Daily Versus Alternate Day Plasma Exchange in Wilson Disease With Acute Liver Failure in Children: A Randomized Controlled Trial

Wilson disease in children has a varied presentation. Wilson disease with acute liver failure is associated with very high mortality and morbidity. The standard therapy i.e chelation (with either D- penicillamine or trientene can be used as a temporizing agent to treat the enormous release of copper into the blood stream; however, substantial removal is not achieved for at least 1 to 3 months. Plasma exchange provides a means of rapid means of removal of copper. As per American Society for Apheresis, TPE in wilson disease with acute liver failure can rapidly remove an average of 20 mg of copper per TPE treatment. Decreased serum copper may decrease hemolysis, prevent progression of kidney failure and provide clinical stabilization. TPE can also remove large molecular weight toxins (aromatic amino acids, ammonia, endotoxins) and other factors, which may be responsible for hepatic coma. The frequency of said TPE is not defined as most evidence is based on case reports and case series.

Copper is highly protein bound and the volume of distribution for copper is large. Under normal conditions, 90-95% of serum copper is ceruloplasmin-bound with the remaining 5-10% being nonceruloplasmin-bound. TPE efficiently removes both ceruloplasmin- and albumin-bound copper. FFP used for exchange can be helpful in treating the associated coagulopathy. TPE has been used as a bridge to liver transplantation as well as seen to improve survival with native liver, the optimum protocol for same remains uncertain.

Study population: Children aged 3 to 18 years with Wilson disease (diagnosed as per Leipzig score >=4) with fulminant presentation (as defined by New Wilson Index>= 11 and INR >= 2.5 ).

Adverse effects: Therapeutic plasma exchange has been shown to be safe and effective in improving native liver survival in Wilson disease patients and is currently standard of care in patients with wilson disease with acute liver failure. However, TPE can be associated with risk of adverse events like infections, fluid overload or circulatory insufficiency, hypersensitivity to blood products.

Stopping rule:

1. Septic Shock
2. Anaphylaxis to blood products
3. HE grade3/4
4. INR > 5 any time point
5. INR >3.5 24 hours after 3 HVP Patients fulfilling criteria 3, 4 and 5 would be listed for liver transplantation. In case of 1, 2 appropriate medical management will be done as per department protocol.

Intervention:

Group 1: Daily plasma exchange + SMT (Maximum 3+1 sessions during a period of 7 days) Group 2: Alternate day therapeutic plasma exchange + SMT

Inclusion Criteria:

1. Wilson disease with New Wilson Index of ≥ 11 and INR ≥ 2.5
2. Children aged 3 years to 18 years

Exclusion Criteria:

1. Grade 3 or grade 4 hepatic encephalopathy
2. Septic shock
3. Disseminated intravascular coagulation
4. Marked hemodynamic instability requiring a high dose of vasopressors (norepinephrine >0.5 mcg/kg/min)
5. Any severe cardio-pulmonary pre-existing disease