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. 2012 Oct;16(4):342-6.

Virologic response and resistance to lamivudine in patients with chronic hepatitis B: a ten-year retrospective analysis

E Gigi  1 , A Sykia, E Sinakos, G Koumerkeridis, M Raptopoulou-Gigi, Al Bellou, D Mougiou, E Orfanou, E Vrettou
Affiliations

Virologic response and resistance to lamivudine in patients with chronic hepatitis B: a ten-year retrospective analysis

E Gigi et al. Hippokratia. 2012 Oct.

Abstract

Background: Emergence of resistance was recognized shortly after the introduction of lamivudine. This 10 year retrospective study investigates resistance to lamivudine and the modifications of antiviral strategies required.

Patients and methods: Two hundred and nine patients were treated with lamivudine. Sixty seven out of 209 patients were excluded from the present study. HBVDNA was tested using the PCR assay and genotypic resistance was performed using the direct PCR sequencing.

Results: In the 125 patients initially treated with lamivudine monotherapy: Α) 48 (38.4%) patients with a mean time of 63.6±26.2 months under lamivudine treatment have normal ALT levels with negative (19%) or low (<1X102) HBVDNA levels, 10% developed cirrhosis, 1 HCC and 6% cleared HBsAg. Β) Resistance was developed in 61.60% patients within 45±23.84 months of lamivudine treatment. These patients were: 1) either switched to adefovir (9), entecavir (2) or tenofovir (2) or adefovir was added to lamivudine (21) for a short time and then they were switched to adefovir alone. Six out of 34 patients developed cirrhosis and 4 HCC while on treatment. 2) or adefovir was added-on to lamivudine (43). In 39 out of 43 treatment is ongoing while on virological response. No one developed cirrhosis or HCC. C) Seventeen patients received de novo combination therapy with lamivudine and adefovir and 2 out of 17 (11.7%) showed resistance to adefovir after 24 months of therapy.

Conclusions: Our results showed that a) approximately 38.4% of patients maintain viral suppression more than 5 years of lamivudine treatment and b) rescue therapy with add-on adefovir to ongoing lamivudine, seems to be a better treatment strategy associated with long term benefit regarding disease complications.

Keywords: Hepatitis B; adefovir; lamivudine; rescue therapy; resistance; treatment.

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Figures

Figure 1
Figure 1. Schematic patient chart enrolled in the study.
Figure 2
Figure 2. Time to lamivudine resistance with Kaplan-Meier curve
Figure 3
Figure 3. Development of resistance to lamivudine per-every 10 months of follow-up.
Figure 4
Figure 4. Development of cirrhosis per therapeutic strategy for resistance to lamivudine.
See this image and copyright information in PMC

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