Liver transplantation for hepatitis B cirrhosis: clinical sequela of passive immunization

Aggressive administration of hepatitis B immune globulin (HBIg) has been shown to prevent hepatitis B viral (HBV) infection of the allograft; however, the clinical sequela of such therapy has not been previously described. We reviewed our experience with high dose, intravenous infusion of an intramuscular HBIg preparation to assess the effectiveness and complications of such therapy. Thirty three orthotopic liver transplants (OLTx) were performed in 32 patients with chronic HBV cirrhosis at the University of Virginia between March 1990 and June 1995. Twenty-nine of 32 (91%) patients remain free of HBV recurrence (defined by undetectable serum HBsAg and HBV-DNA) after a mean of 21 months (2-54 months), with one patient requiring retransplantation. Three (10%) patients died of non-HBV causes (two vascular events, one infectious event). Twenty episodes of acute cellular rejection were treated in 18 patients (two had two episodes). Sixteen rejections occurred within 18 d of transplant, 19 by day 120, and one late rejection occurred at 18 months owing to medication non-compliance. Eighteen patients had at least one documented infection. Six patients were treated for CMV infection (five empirically). Eight patients were treated for HSV infections (seven mild herpetic labialis and one herpetic keratitis). Four patients had documented fungal infection (one mucormycosis pneumonia and three minor superficial mucosal infections). With the exception of one necrotizing pneumonia, 11 bacterial infections were successfully treated with conventional antimicrobial agents. No patient developed post-transplant lymphoproliferative disorder. Symptoms associated with HBIg infusion were intermittent but frequent and consisted of myalgias, predominantly back pain (90%), headache (20%) and flushing (5%). No patient experienced anaphylaxis, fever, rash, arthritis or hypotension. Despite the potential for mercury toxicity and HCV transmission in the HBIg formulations currently available in the United States, serum mercury levels remained below standards for industrial exposure (60 micrograms/ml), and only one individual developed post-transplant HCV infection after receiving multiple units of unscreened blood prior to 1991.

High-dose HBIg prevented HBV infection of the allograft in 29 of 32 patients transplanted for HBV cirrhosis with three non-HBV associated deaths. The intravenous infusion of HBIg was frequently associated with minor side effects that were safely tolerated by patients. The risk of HCV transmission and mercury toxicity are minimal, but support the need for a new intravenous formulation of HBIg. HBIg therapy successfully decreased post-OLTx HBV recurrence with no clinical events associated with immunosuppression. Patients did non experience allergic or infusion-related complications that altered or terminated therapy. Manufacturing modifications of HBIg may allow for improved patient tolerance and decreased risks.