Hepatitis B and liver transplantation: Molecular and clinical features that influence recurrence and outcome

Table 1 Three protocols for prevention of recurrent hepatitis B virus infection after liver transplantation

HBIG-indefinite (HBIG continued for life)	HBIG 10000 IU iv during anhepatic phase;
	then 5000 IU iv daily for 5 d; followed by 800 IU im monthly indefinitely
	Plus
	ETV or TFV indefinitely
HBIG-light (HBIG for first 6 mo only)	HBIG 10000 IU iv during anhepatic phase;
	then 5000 IU iv daily for 5 d; followed by 800 IU im monthly for 6 mo
	Plus
	ETV and/or TFV indefinitely
HBIG-free (No HBIG)	ETV and/or TFV indefinitely

ETV: Entecavir; HBIG: Hepatitis B immune globulin; im: Intramuscular; iv: Intravenous; TFV: Tenofovir. The appropriate annual costs of these are set out in Table 2.

Table 2 Approximate annual costs ($USD) for three post-transplant protocols for hepatitis B virus prophylaxis

Costs for the first year
HBIG-indefinite	HBIG 10K	7051	5K IU	$17628	800 IU monthly	$6723	ETV, TFV	$9900	$41302 ($31059-$51545)
HBIG-light	HBIG 10K	7051	5K IU	$17628	800 IU × 6 monthly	$3385	ETV, TFV	$9900	$37964 ($28549-$47379)
HBIG-free	None	None	None	None	None	None	ETV, TFV	$9900	$9900
Costs in the subsequent years
HBIG-indefinite	None	None	None	None	800 IU monthly	$6723	ETV, TFV	$9900	$16623 ($14097-$19149)
HBIG-light	None	None	None	None	None	None	ETV, TFV	$9900	$9900
HBIG-free	None	None	None	None	None	None	ETV, TFV	$9900	$9900

ETV: Entecavir; HBIG: Hepatitis B immunoglobulin; iv: Intravenous; im: Intramuscular; 1K: 1000 units; 10K: 10000 units; TFV: Tenofovir; NAs: Nucleotide analogues. These costs will be approximately doubled if two NAs are administered.

Table 3 Proposed individualized protocols for prophylaxis of hepatitis B virus recurrence post- liver transplantation, based on risk of recurrence

HBV recurrence risk	First 6 mo post-LT	Withdrawal of HBIG
High-risk:
Resistant mutations pre-LT	HBIG-Light	Combination of NAs
HCC at transplant	Plus	(ETV + TFV)
HDV/HBV co-infection	Monotherapy with NA (ETV or TFV)
HIV/HBV co-infection
Non-adherence
Moderate-risk:
HbcAb + donors into HbsAb-recipients	HBIG-Light	Monotherapy with NA
Early post-LT renal dysfunction requiring	Plus	(ETV or TFV)
Indentation NA dose adjustment	Monotherapy with NA (ETV or TFV)
Low risk:
Undetectable HBV DNA at transplant	HBIG-free	Monotherapy with NA
HbcAb + donors into HbsAb + recipients	Monotherapy with NA (ETV or TFV)	(ETV or TFV)
Unknown risk:
HBV naïve donor into HbcAb + recipient	None	None

Ab: Antibody; ETV: Entecavir; HBIG: Hepatitis B immune globulin; HBc: Hepatitis B core; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HDV: Hepatitis D (delta agent); LT: Liver transplantation; NAs: Nucleotide analogues; TFV: Tenofovir; HIV: Human immunodeficiency virus.