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Impact of prior lamivudine use on the antiviral efficacy and development of resistance to entecavir in chronic hepatitis B patients.

Hwang JA, Kim KB, Yang MJ, Lim SG, Hwang JC, Cheong JY, Cho SW, Kim SS - Clin Mol Hepatol (2015)

Bottom Line: In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149).However, prior LAM use without refractoriness did not affect the development of ETV resistance.The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

ABSTRACT

Background/aims: To determine the efficacies of entecavir (ETV) in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B (CHB) patients and in those with prior lamivudine (LAM) use who did not develop resistance.

Methods: We retrospectively enrolled 337 patients with CHB who were treated with ETV (0.5 mg daily) for at least 30 months. The study included 270 (80.1%) NA-naïve patients and 67 (19.9%) LAM-use patients. Ten of the LAM-use patients were refractory to LAM therapy without developing resistance.

Results: Genotypic resistance to ETV developed more frequently in the LAM-use group (13.1%) than in the NA-naïve group (2.6%) at 60 months (P=0.009). In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149). Prior LAM refractoriness and a higher hepatitis B virus DNA level at month 12 were independent predictive factors for the development of ETV resistance.

Conclusions: ETV resistance developed more frequently in LAM-use patients with CHB. However, prior LAM use without refractoriness did not affect the development of ETV resistance. The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier curves for the cumulative probabilities of virological breakthrough and the development of entecavir (ETV) resistance. (A) Comparison of cumulative probabilities of virological breakthrough during ETV treatment between the nucleos(t)ide (NA)-naïve group and lamivudine (LAM)-use group (with or without refractoriness) in all study populations. (B) Comparison of the incidence of ETV resistance between the NA-naïve group and the LAM-use group (with or without refractoriness) in the study population. (C) Comparison of the cumulative probabilities of virological breakthrough during ETV therapy after excluding patients with prior lamivudine experience in the NA-naïve and LAM-use groups. (D) Comparison of the cumulative probabilities of ETV resistance during ETV therapy after excluding patients with prior lamivudine experience in the NA-naïve group and LAM-use group. VB, virologic breakthrough.
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Figure 3: Kaplan-Meier curves for the cumulative probabilities of virological breakthrough and the development of entecavir (ETV) resistance. (A) Comparison of cumulative probabilities of virological breakthrough during ETV treatment between the nucleos(t)ide (NA)-naïve group and lamivudine (LAM)-use group (with or without refractoriness) in all study populations. (B) Comparison of the incidence of ETV resistance between the NA-naïve group and the LAM-use group (with or without refractoriness) in the study population. (C) Comparison of the cumulative probabilities of virological breakthrough during ETV therapy after excluding patients with prior lamivudine experience in the NA-naïve and LAM-use groups. (D) Comparison of the cumulative probabilities of ETV resistance during ETV therapy after excluding patients with prior lamivudine experience in the NA-naïve group and LAM-use group. VB, virologic breakthrough.

Mentions: During the ETV treatment, virological breakthrough occurred in four patients in the NA-naïve group and six patients in the LAM-use group. The cumulative probabilities of virological breakthrough at months 36, 48, and 60 were 0.4%, 2.2%, and 3.5% in the NA-naïve group, 3.1%, 15.8%, and 15.8% in the LAM-use group. Virological breakthrough occurred more frequently in the LAM-use group than in the NA-naïve group (log rank P=0.001) (Fig. 3A). Among the 10 patients who developed virological breakthrough, genotypic ETV resistance was demonstrated in seven (three NA-naïve and four LAM-use patients). ETV resistance occurred more frequently in the LAM-use group compared to the NA-naïve group (log rank P=0.009). The cumulative probabilities of ETV resistance at months 36, 48 and 60 were 0.4%, 1.3%, and 2.6% in NA-naïve group and 0.0%, 13.1%, and 13.1% in the LAM-use group (Fig. 3B).


Impact of prior lamivudine use on the antiviral efficacy and development of resistance to entecavir in chronic hepatitis B patients.

Hwang JA, Kim KB, Yang MJ, Lim SG, Hwang JC, Cheong JY, Cho SW, Kim SS - Clin Mol Hepatol (2015)

Kaplan-Meier curves for the cumulative probabilities of virological breakthrough and the development of entecavir (ETV) resistance. (A) Comparison of cumulative probabilities of virological breakthrough during ETV treatment between the nucleos(t)ide (NA)-naïve group and lamivudine (LAM)-use group (with or without refractoriness) in all study populations. (B) Comparison of the incidence of ETV resistance between the NA-naïve group and the LAM-use group (with or without refractoriness) in the study population. (C) Comparison of the cumulative probabilities of virological breakthrough during ETV therapy after excluding patients with prior lamivudine experience in the NA-naïve and LAM-use groups. (D) Comparison of the cumulative probabilities of ETV resistance during ETV therapy after excluding patients with prior lamivudine experience in the NA-naïve group and LAM-use group. VB, virologic breakthrough.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493356&req=5

Figure 3: Kaplan-Meier curves for the cumulative probabilities of virological breakthrough and the development of entecavir (ETV) resistance. (A) Comparison of cumulative probabilities of virological breakthrough during ETV treatment between the nucleos(t)ide (NA)-naïve group and lamivudine (LAM)-use group (with or without refractoriness) in all study populations. (B) Comparison of the incidence of ETV resistance between the NA-naïve group and the LAM-use group (with or without refractoriness) in the study population. (C) Comparison of the cumulative probabilities of virological breakthrough during ETV therapy after excluding patients with prior lamivudine experience in the NA-naïve and LAM-use groups. (D) Comparison of the cumulative probabilities of ETV resistance during ETV therapy after excluding patients with prior lamivudine experience in the NA-naïve group and LAM-use group. VB, virologic breakthrough.
Mentions: During the ETV treatment, virological breakthrough occurred in four patients in the NA-naïve group and six patients in the LAM-use group. The cumulative probabilities of virological breakthrough at months 36, 48, and 60 were 0.4%, 2.2%, and 3.5% in the NA-naïve group, 3.1%, 15.8%, and 15.8% in the LAM-use group. Virological breakthrough occurred more frequently in the LAM-use group than in the NA-naïve group (log rank P=0.001) (Fig. 3A). Among the 10 patients who developed virological breakthrough, genotypic ETV resistance was demonstrated in seven (three NA-naïve and four LAM-use patients). ETV resistance occurred more frequently in the LAM-use group compared to the NA-naïve group (log rank P=0.009). The cumulative probabilities of ETV resistance at months 36, 48 and 60 were 0.4%, 1.3%, and 2.6% in NA-naïve group and 0.0%, 13.1%, and 13.1% in the LAM-use group (Fig. 3B).

Bottom Line: In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149).However, prior LAM use without refractoriness did not affect the development of ETV resistance.The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

ABSTRACT

Background/aims: To determine the efficacies of entecavir (ETV) in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B (CHB) patients and in those with prior lamivudine (LAM) use who did not develop resistance.

Methods: We retrospectively enrolled 337 patients with CHB who were treated with ETV (0.5 mg daily) for at least 30 months. The study included 270 (80.1%) NA-naïve patients and 67 (19.9%) LAM-use patients. Ten of the LAM-use patients were refractory to LAM therapy without developing resistance.

Results: Genotypic resistance to ETV developed more frequently in the LAM-use group (13.1%) than in the NA-naïve group (2.6%) at 60 months (P=0.009). In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149). Prior LAM refractoriness and a higher hepatitis B virus DNA level at month 12 were independent predictive factors for the development of ETV resistance.

Conclusions: ETV resistance developed more frequently in LAM-use patients with CHB. However, prior LAM use without refractoriness did not affect the development of ETV resistance. The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.

No MeSH data available.


Related in: MedlinePlus