Antiviral treatment for chronic hepatitis B in renal transplant patients

Table 1 Dosage adjustment of nucleos(t)ide analogue for patients with reduced creatinine clearance

	Recommended dosage		Dosage forms
Creatinine clearance (mL/min)	Lamivudine[25]		Lamivudine[25]
> 50	100 mg once daily		Tablets: 100 mg
30-49	100 mg first dose, then 50 mg once daily		Oral solution: 10 mg/mL
15-29	100 mg first dose, then 25 mg once daily
5-14	35 mg first dose, then 15 mg once daily
< 5	35 mg first dose, then 10 mg once daily
	Adefovir[26]		Adefovir[26]
> 50	10 mg every 24 h		Tablets: 10 mg
30-49	10 mg every 48 h		Oral solution: not available
10-29	10 mg every 72 h
Hemodialysis	10 mg every 7 d following dialysis
	Telbivudine[27]		Telbivudine[27]
> 50	600 mg every 24 h		Tablets: 600 mg
30-49	600 mg every 48 h		Oral solution: 100 mg/5 mL
10-29	600 mg every 72 h
Hemodialysis	600 mg every 96 h following dialysis
	Entecavir[28]	Entecavir in Lamivudine-Refractory[28]	Entecavir[28]
> 50	0.5 mg once daily	1 mg once daily	Tablets: 0.5 mg and 1 mg Oral solution: 0.05 mg/mL
30-49	0.25 mg once daily OR	0.5 mg once daily OR
	0.5 mg every 48 h	1 mg every 48 h
10-29	0.15 mg once daily OR	0.3 mg once daily OR
	0.5 mg every 72 h	1 mg every 72 h
Hemodialysis	0.05 mg once daily OR	0.1 mg once daily OR
	0.5 mg every 7 d following dialysis	1 mg every 7 d following dialysis
	Tenofovir[29]		Tenofovir[29]
> 50	300 mg every 24 h		Tablets: 300 mg
30-49	300 mg every 48 h		Oral powder: 40 mg per 1 g of oral powder
10-29	300 mg every 72 to 96 h
Hemodialysis	300 mg every 7 d or after approximately 12 h of dialysis

Table 2 Definition of response to nucleos(t)ide analogue antiviral therapy of chronic hepatitis B

Category of response
Biochemical (BR)	Decrease in serum ALT to within the normal range
Virologic (VR)	Decrease in serum HBV DNA to undetectable
	levels by PCR assays, and loss of HBeAg in
	patients who were initially HBeAg positive
Primary non-response	Decrease in serum HBV DNA by 2 log10 IU/mL
	after at least 24 wk of therapy
Virologic relapse	Increase in serum HBV DNA of 1 log10 IU/mL
	after discontinuation of treatment in at least
	two determinations more than 4 wk apart
Histologic (HR)	Decrease in histology activity index by at least 2
	points and no worsening of fibrosis score
	compared to pre-treatment liver biopsy
Complete (CR)	Fulfill criteria of biochemical and virological
	response and loss of HBsAg
Time of assessment
On-therapy	During therapy
Maintained	Persist throughout the course of treatment
End-of-treatment	At the end of a defined course of therapy
Off-therapy	After discontinuation of therapy
Sustained (SR-6)	6 mo after discontinuation of therapy
Sustained (SR-12)	12 mo after discontinuation of therapy

HBV: Hepatitis B; HBsAg: Hepatitis B surface antigen.

Table 3 Definition of terms relating to antiviral resistance to nucleos(t)ide analogue treatment

Term	Definition
Virologic breakthrough	Increase in serum HBV DNA by > 1 log10 (10-fold) above nadir after achieving virologic response, during continued treatment
Viral rebound	Increase in serum HBV DNA to > 20000 IU/mL or above pretreatment level after achieving virologic response, during continued treatment
Biochemical breakthrough	Increase in ALT above upper limit of normal after achieving normalization, during continued treatment
Genotypic resistance	Detection of mutations that have been shown in “in vitro” studies to confer resistance to the NA that is being administered
Phenotypic resistance	In vitro confirmation that the mutation detected decreases susceptibility (as demonstrated by increase in inhibitory
	concentrations) to the NUC administered

NUC: Nucleos(t)ide analogue.