Considerations for the long-term treatment of chronic hepatitis B with nucleos(t)ide analogs

Figures & data

Figure 1. Cumulative annual incidence of resistance of nucleos(t)ide analogs.

Data for telbivudine are through year 2, and for adefovir and tenofovir through year 5.

Data taken from [15,16,56–60].

Table 1. Virologic, biochemical and serologic effectiveness of long-term entecavir therapy in nucleos(t)ide-naive patients with chronic hepatitis B.

Study design	Patients	ETV arm (n)	Treatment duration, mean (years)	Outcomes					Ref.
				Undetectable HBV DNA (%)	ALT ≤1.0 × ULN (%)	HBeAG loss	HBeAG SC (%)	HBeAG loss (n)
Randomized, comparative Phase III trial, followed by open-label rollover (NC = M)	HBeAg(+)	146	5	94^†	80	NR^‡	23^‡	2^‡	[48]
European cohort study	HBeAg(+) or HBeAg(-)	418	Median: 3.5	97^§	88	NR	56^¶	12^¶	[49]
Hong Kong cohort study (prospective, open-label)	HBeAg(+) or HBeAg(-)	222	4	96^§	91	NR	52	1	[50]
Randomized, noncomparative Phase II trial, followed by open-label rollover (NC = M)	Japanese HBeAg(+) or HBeAg(-)	167	3	88^#	90	39^††	26^††	1	[51]

^†<300 copies/ml.

^‡Patients who had lost HBeAg or HBsAg during years 1 or 2 of the Phase III trial discontinued study therapy and did not enrol in the long-term analysis.

^§<12 IU/ml.

^¶Kaplan–Meier estimate.

^#<400 copies/ml.

^††Among those HBeAg(+) at baseline.

ALT: Alanine aminotransferase; ETV: Entecavir; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; M: Missing; NC: Noncompleter; NR: Not reported; SC: Seroconversion; ULN: Upper limit of normal.

Table 2. Virologic, biochemical and serologic effectiveness of long-term tenofovir therapy in nucleos(t)ide-naive patients with chronic hepatitis B.

Study design	Patients	N (TDF arm)	Treatment duration	Outcomes					Ref.
				Undetectable HBV DNA (%)	ALT ≤1.0 × ULN (%)	HBeAG loss (%)	HBeAG SC (%)	HBeAG loss (number of patients)
Comparative, randomized Phase III trial, followed by open-label rollover (on-treatment analysis; missing = excluded)	HBeAg(+) or HBeAg(-)	218^† (327 total)	Up to 5 years	98^‡,§	79	51	40	11^¶	[53]
Retrospective/prospective cohort	HBeAg(+) or HBeAg(-) ± cirrhosis or HCC	302	Median: 28 months	91^#	NR	NR	33	7	[54]

^†Number of patients entering final year.

^‡<400 copies/ml.

^§Includes 19 patients who added emtricitabine.

^¶Kaplan−Meier estimate.

^#<12 IU/ml.

ALT: Alanine aminotransferase; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; NR: Not reported; SC: Seroconversion; TDF: Tenofovir; ULN: Upper limit of normal.

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Chang TT, Lai CL, Kew Yoon S et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology 51(2), 422–430 (2010).

 PubMed Web of Science ®Google Scholar

Lampertico P, Vigano M, Soffredini R et al. Entecavir monotherapy for nuc-naive chronic hepatitis B patients from field practice: high efficacy and favorable safety profile over 3 years. Hepatology 54 (Suppl. 1), Abstract 1436 (2011).

 Google Scholar

Seto WK, Lai CL, Fung J, Yuen JC, Wong DK, Yuen MF. Outcome of 4-year treatment of entecavir for treatment-naive chronic hepatitis B. J. Hepatol. 54, S301 (2011).

 Web of Science ®Google Scholar

Yokosuka O, Takaguchi K, Fujioka S et al. Long-term use of entecavir in nucleoside-naive Japanese patients with chronic hepatitis B infection. J. Hepatol. 52(6), 791–799 (2010).

 PubMed Web of Science ®Google Scholar

Marcellin P, Buti M, Gane EJ et al. Five years of treatment with tenofovir DF (TDF) for chronic hepatitis B (Chb) infection is associated with sustained viral suppression and significant regression of histological fibrosis and cirrhosis. Hepatology 54 (Suppl. 1), Abstract 1375 (2011).

 PubMedGoogle Scholar

Lampertico P, Soffredini R, Viganò M et al. 2-year effectiveness and safety of tenofovir in 302 NUC-naive patients with chronic hepatitis B: a multicenter European study in clinical practice. Hepatology 54 (Suppl.), 1041A (2011).

 Google Scholar