Efficacy and Safety of Lamivudine on Replication of Recurrent Hepatitis B After Cadaveric Renal Transplantation

Abstract

Lamivudine therapy was associated with (i) a normalization of alanine aminotransferase levels in four of five patients when these levels were increased at the beginning (n=5); (ii) a rapid disappearance of HBV DNA from the serum (detected by hybridization) in all of the patients; (iii) the negativity of HBV DNA by polymerase chain reaction in four patients; and (iv) no change in renal function and in proteinuria when present (one patient). Finally, no adverse effects were noted. When lamivudine therapy was stopped for four patients after 6 months, it was associated with a biochemical and virological relapse within the weeks that followed. Lamivudine therapy was therefore resumed for these patients.

Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients

“…34,35 Lamivudine is effective and well tolerated in renal allograft recipients. 12,13,15 However, the optimal timing to start or stop treatment remains obscure. Early treatment seems advisable, because lifethreatening complications may not be averted by treatment that is started after the development of severe liver disease.…”

“…The high incidences of relapses following treatment withdrawal reported by different investigators have resulted in the common practice of continuing lamivudine in these patients indefinitely. 12,19 We therefore selected HBeAg-negative patients on low-dose immunosuppression who had virologic and clinical response for a trial of stopping lamivudine. Our data show that 44.4% of patients satisfied the selection criteria and that treatment could be successfully withdrawn in 18.5%.…”

“…10,11 Short-term studies have shown virologic and biochemical efficacy in small series of renal transplant recipients. [12][13][14][15][16] We and others have reported favorable results with lamivudine in the treatment of fibrosing cholestatic hepatitis B, which hitherto has been associated with nearly uniform mortality. 17,18 However, many critical issues remain unresolved.…”

“…At present, lamivudine is often administered prophylactically at the time of kidney transplantation and continued indefinitely in view of the high rate of relapse after discontinuation. 12,19 Although this approach is clinically convenient, its scientific validity has not been substantiated, and the emergence of lamivudineresistant HBV variants with prolonged treatment is an escalating problem. 15,20 Because it would not be ethical to conduct placebocontrolled studies to examine these issues, we have devised a protocol for HBsAg-positive renal transplant recipients so that lamivudine therapy can be commenced early in patients with evidence of accelerated HBV replication, concomitant with or before the development of overt clinical hepatitis.…”

Viral Infection in the Renal Transplant Recipient

“…Lamivudine is effective in normalizing aminotrans-ferases and eliminating HBV DNA (167,168). Lamivudine resistance has emerged; in one study of renal transplant recipients, half of the patients had resistance 17 mo after initiating therapy (169).…”