Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger?

Table 1 Main virological and biochemical features in the different clinical phases of chronic hepatitis B in HBsAg+ patients

Phase 1: Immune tolerant	Phase 2: Immune active	Phase 3: Asymptomatic carrier	Phase 4: HBV reactivation
HBeAg+	Attempt to remove HBeAg	HBeAg-	HBeAg+ or -
HBV-DNA ≥ 108 IU/mL	HBV-DNA ↓	HBV-DNA < 2000 IU/mL	HBV-DNA ↑
Normal LFTs→ no damage	Altered LFTs→ damage	Normal LFTs→ no damage	Altered LFTs→ damage

HBV: Hepatitis B virus; LFT: liver function tests

Table 2 Main studies examining prophylaxis minimization in hepatitis B virus liver transplanted patients, employing different approaches

Specific aim	Ref.	Number of patients	Method	Main results
HBIG minimization	Di Paolo et al[71]	11	HBIG administration on demand (when HBsAb < 70 IU/L) with Lam	No HBV reactivation (1 yr F/U)
	Gane et al[72]	147	Very-low HBIG dose (400-800 IU monthly) with Lam	4% of HBV recurrence (5 yr F/U)
High-genetic barrier nucleos(t)ide analogues monotherapy	Fung et al[73,74]	80	ETV monotherapy	92% HBsAg-100%HBV-DNA undetectable (8 yr F/U)
	Teperman et al[75]	40	TDF monotherapy after HBIG discontinuation	No change (72 wk F/U)
	Manini et al[77]	77	ETV or TDF monotherapy after HBIG discontinuation	100%HBV-DNA undetectable 9% HBsAg reappearance (5 yr F/U)
Complete withdrawal of HBV prophylaxis	Lenci et al[81,82]	30	Sequential discontinuation of HBIG and Lam in low risk (cccDNA negative) patients	90% successful withdrawal 60% HBsAb > 10 IU (6 yr F/U)

cccDNA: Covalently closed circular DNA; HBV: Hepatitis B virus; ETV: Entecavir; F/U: Follow-up; HBIG: HBsAb immunoglobulin; Lam: Lamivudine; TDF: Tenofovir dipivoxyl.