New approaches in the management of chronic hepatitis B: role of tenofovir

Figures & data

Figure 1 The natural of history of chronic hepatitis B virus infection.

Abbreviations: HBV, chronic hepatitis B virus; HBeAg, hepatitis B e antigen; ALT, alanine aminotransferase.

Table 1 One year efficacy, advantages, and disadvantages of approved treatments of chronic hepatitis B

	Peg-IFN		Lamivudine		Adefovir		Entecavir		Telbivudine		Tenofovir
	e(+)	e(−)	e(+)	e(−)	e(+)	e(−)	e(+)	e(−)	e(+)	e(−)	e(+)	e(−)
Dose/route	subcutaneous		oral		oral		oral		oral		oral
HBV DNA
Log reduction	2.4	2.3	5.4–5.8	4.2–4.5	3.6	3.7	6.9	5.0	6.5	5.2	NA	NA
Undetectable^a	14%	19%	40%	73%	12%–21%	51%–59%	67%	90%	60%	88%	74%	92%
HBeAg seroconversion	32%	NP	18%–22%	NP	12%–18%	NP	21%	NP	23%	NP	21%	NP
HBsAg seroconversion	3.0%	2.8%	0%	0%	0%	0%	0%	0%	0%	0%	0%	0%
ALT normalization	41%	59%	60%–75%	73%–79%	48%–54%	72%–78%	68%	78%	77%	74%	69%	77%
Side effects	Many		Negligible		Nephrotoxicity		Negligible		Negligible		Nephrotoxicity
Drug resistance
Year 1	NA		24%		0%		0.1%		6.8%		0%
Year 2	NA		42%		3%		0.3%		17%		0%
Year 3	NA		53%		11%		0.4%		NA		NA
Year 4	NA		70%		18%		0.8%		NA		NA
Year 5	NA		74%		29%		1.2%		NA		NA

a Undetectable HBV DNA is defined as less than 400 copies/mL. Studies on entecavir and telbivudine used 300 copies/mL.

Abbreviations: ALT, alanine aminotransferase; HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; NA, not applicable; NP, not possible; Peg-IFN, pegylated interferon.

Table 3 Recommendations for administration of tenofovir disiproxil fumarate 300 mg to patients with renal impairment

Clinical condition	Administration interval
CLcr (mL/min)^a
> 50	Every 24 h
30–49	Every 48 h
10–29	Twice weekly
ESRD requiring hemodialysis	Every 7 days or after a total of approximately 12 h of dialysis

a Creatinine clearance.

Abbreviation: ESRD, end stage renal disease.

Figure 2 Study design of two randomized trials comparing the efficacy of tenofovir to adefovir in both HBeAg-positive and HBeAg-negative chronic hepatitis B patients. At or after week 72 there is an option to initiate emtricitabine–tenofovir combination therapy for confirmed HBV DNA > 400 copies/mL. Current follow-up is up to 96 weeks of treatment.

Abbreviations: HBeAg, hepatitis B e antigen.

Table 2 Clinical efficacy of tenofovir in nucleos(t)ide-naïve patients with chronic hepatitis B

Drug	Number of patients	Histological improvement			Undetectable HBV DNA (<400 copies/mL)^b			HBeAg-seroconversion			HBsAg loss
		Week 48	Week 72	Week 96	Week 48	Week 72	Week 96	Week 48	Week 64	Week 96	Week 48	Week 64	Week 96
HBeAg (+) patients
TDF-TDF^a	176	74	NA	NA	76	79 (89)	77 (89)	21	26	27	3	5	6
ADV-TDF^a	90	68	NA	NA	13	76 (82)	78 (85)	18	21	22	0	0	6
p-value		NS			p < 0.001	NS	NS	NS	NS	NS	p = 0.02	p = 0.004	NS
HBeAg (−) patients
TDF-TDF^a	250	72	NA	NA	93	91 (98)	90 (98)	NA	NA	NA	0	0	0
ADV-TDF^a	125	69	NA	NA	63	88 (98)	89 (98)	NA	NA	NA	0	0	0
p-value		NS			p < 0.001	NS	NS				NS	NS	NS

Notes: All results are presented in proportions of patients.

a Patients were randomized to initiate either with TDF or with ADV for the first 48 weeks and switch to TDF thereafter.

b Results are presented in proportions of patients: intention-to-treat (patients on therapy).

Abbreviations: HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; NA, not applicable; NS, not significant; ADV, adefovir dipivoxil; TDF, tenofovir disproxil fumarate.