Evolution of hepatitis B management in kidney transplantation

Table 1 The major clinical trials regarding the use of oral nucleoside/tides for HBsAg-positive kidney transplant recipients

Oral Nucleoside/tides	Study design	n	Major treatment outcomes
Lamivudine
Rostaing et al[32] (1997)	Prospective	6	LAM as initial Rx → ALT normalization and HBV DNA undetectability in 4/6 patients
Chan et al[1] (2002)	Prospective	11	LAM as initial Rx → ALT normalization and HBV DNA undetectability in all patients; e-seroconversionrate (21.4%); markedly improved patient survival when compared to historical controls who had no anti-viral Rx (P < 0.001)
Fabrizi et al[33] (2004)	Meta-analysis	184	LAM as initial Rx → HBV-DNA undetectability [91% (95%CI: 86%-96%)], ALT normalization [81% (95%CI: 70%-92%)] and LAM-resistance [18% (95%CI: 10%-37%)] after 12 mo; e-seroconversion rate (0%-46%) in 4 trials
Thabut et al[34] (2004)	Prospective	14	LAM as initial Rx → HBV undetectability (57%) andALT normalization (57%) after 3 mo; LAM-resistance (57%) after median of 15 mo
Filik et al[31] (2006)	Prospective	15	LAM as initial Rx → HBV DNA undetectability (46.7%) after 2 yr
Yap et al[24] (2010)	Retrospective	38	LAM as initial Rx → LAM-resistance (64%) after 4 yr; improved long-term patient survival (83% vs 34% at 20-yr, P = 0.006) when compared to historical controls who had no anti-viral Rx
Adefovir
Fontaine et al[37] (2005)	Prospective	11	ADV as mono-therapy for LAM-resistant KTR → 5 log ↓ HBV DNA after 1 yr, only 1 patient had transient deterioration of allograft function
Kamar et al[40] (2009)	Prospective	11	ADV for LAM-resistant KTR → significant ↓ in HBV DNA (P = 0.01) and ALT normalization after 12 mo, ↑serum creatinine and proteinuria after 24 mo (P = 0.02)
Tse et al[43] (2010)	Retrospective	4	ADV for LAM-resistant KTR → 4 log ↓ HBV DNA and significant ↓ ALT levels (P = 0.029) after 18 mo, no significant change in allograft function
Lampertico et al[41] (2011)	Prospective	11	ADV as add-on Rx to LAM for LAM-resistant KTR → HBV undetectability (88%) after 3 yr; no significant changes in renal function and proteinuria
Lai et al[42] (2012)	Retrospective	14	ADV as mono- (n = 5) or add-on (n = 9) therapy in LAM-resistant KTR → HBV DNA undetectability [5 (35.7%) and 6 (42.8%) patients]after 12 and 24 mo with no virological breakthrough; ALT normalization in 13 patients (92.8%) after 1 yr; moderate to severe renal insufficiency (29%)
Entecavir
Kamar et al[48] (2008)	Prospective	10	ETV for ADV-resistant (n = 9) or LAM-resistant (n = 1) KTR → HBV DNA undetectability (50%) after 16.5 mo
Hu et al[47] (2012)	Prospective	27	ETV in KTR patients without LAM-resistance → HBV DNA undetectability (96% and 100%) after 12 and 24 mo, with no virological breakthrough
Tenofovir
Daudé et al[52] (2011)	Prospective	3	TFV as mono-therapy → HBV DNA undetectability (43%); no changes in allograft function

ADV: Adefovir; ALT: Alanine transaminase; ETV: Entecavir; LAM: Lamivudine; KTR: Kidney transplant recipients; TFV: Tenofovir; HBV: Hepatitis B virus.