LIVER-TRANSPLANTATION FOR HEPATITIS-B CIRRHOSIS - CLINICAL SEQUELA OFPASSIVE-IMMUNIZATION

Aggressive administration of hepatitis B immune globulin (HBIg) has be en shown to prevent hepatitis B viral (HBV) infection of the allograft ; however, the clinical sequela of such therapy has not been previousl y described. We reviewed our experience with high dose, intravenous in fusion of an intramuscular HBIg preparation to assess the effectivenes s and complications of such therapy, Thirty three orthotopic liver tra nsplants (OLTx) were performed in 32 patients with chronic HBV cirrhos is at the University of Virginia between March 1990 and June 1995. Twe nty-nine of 32 (91%) patients remain free of HBV recurrence (defined b y undetectable serum HBsAg and HBV-DNA) after a mean of 21 months (2-5 4 months), with one patient requiring retransplantation. Three (10%) p atients died of non-HBV causes (two vascular events, one infectious ev ent). Twenty episodes of acute cellular rejection were treated in 18 p atients (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 le ast one documented infection. Six patients were treated for CMV infect ion (five empirically). Eight patients were treated for HSV infections (seven mild herpetic labialis and one herpetic keratitis). Four patie nts had documented fungal infection (one mucormycosis pneumonia and th ree minor superficial mucosal infections). With the exception of one n ecrotizing pneumonia, 11 bacterial infections were successfully treate d with conventional antimicrobial agents. No patient developed post-tr ansplant lymphoproliferative disorder. Symptoms associated with HBIg i nfusion were intermittent but frequent and consisted of myalgias, pred ominantly back pain (90%), headache (20%) and flushing (5%). No patien t experienced anaphylaxis, fever, rash, arthritis or hypotension. Desp ite the potential for mercury toxicity and HCV transmission in the HBI g formulations currently available in the United States, serum mercury levels remained below standards for industrial exposure (60 mu g/ml), and only one individual developed post-transplant HCV infection after receiving multiple units of unscreened blood prior to 1991. Summary: High-dose HBIg prevented HBV infection of the allograft in 29 of 32 pa tients transplanted for HBV cirrhosis with three non-HBV associated de aths. 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 ne ed for a new intravenous formulation of HBIg. HBIg therapy successfull y decreases post-OLTx HBV recurrence with no clinical events associate d with immunosuppression. Patients did not experience allergic or infu sion-related complications that altered or terminated therapy. Manufac turing modifications of HBIg may allow for improved patient tolerance and decreased risks.