Four years of lamivudine treatment in Chinese patients with chronic hepatitis B

Chang, Ting‐Tsung; Lai, Ching–Lung; Chien, Rong‐Nan; Guan, R; Lim, Seng-Gee; Lee, Chuan–Mo; Ng, Keng-Yeen; Nicholls, Graham J.; Dent, J. C.; Leung, Nancy

doi:10.1111/j.1440-1746.2004.03428.x

Cited by 226 publications

(177 citation statements)

References 27 publications

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“…It was observed in other studies that genotypic resistance to LAM increases from 15 to 30% after 1 year of treatment to 70% after 5 years of treatment [2,[22][23][24]. It is almost similar for longer duration but was less for shorter duration because we have studied VBT, whereas others had studied genotypic resistance.…”

Section: Discussionmentioning

confidence: 71%

Pretreatment and on-treatment predictors of viral breakthrough in lamivudine therapy for chronic hepatitis B

et al. 2008

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Purpose There are remarkable advances in the treatment of chronic hepatitis B (CHB) in the last few years. Unfortunately, prolonged antiviral treatment is associated with increasing risk of drug resistance/viral breakthrough (VBT), which may lead to flare-up and rapid decompensation. We have designed this study to predict the pretreatment and on-treatment factors responsible for development of VBT. Methods This study was conducted during the period of February 2000 to November 2007. We have included 423 patients who received lamivudine (LAM) therapy for at least 1 year and at least 2 follow-ups at 6 months' interval. Follow-up period was 12-78 months. Chi-square test, student's t test, and logistic regression analysis were performed to prove the validity. Results Of the 423 study cases, 367 (86.8%) were of male patients and 261 (61.7%) patients were HBeAg positive; the age of the patients was 30.8 ± 12.9 years. Development of VBT was 4. 4, 22.8, 45.3, and 74% at 1, 2, 3, and 4 or more years, respectively. Pretreatment high HBV DNA (P = 0.005) and female sex (P = 0.01) were associated with VBT and pretherapy ALT (P = 0.698), HBeAg status (P = 0.273), and age (P = 0.059) were not associated. Duration of treatment, failure to lose HBeAg at 1 year, and HBV DNA nonresponder at 6 months were significantly (P = 0.001) associated with development of VBT. Conclusion Persistence of HBeAg at 1 year and HBV DNA nonresponder at 6 months are good predictors of development of VBT.

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Section: Discussionmentioning

confidence: 71%

Pretreatment and on-treatment predictors of viral breakthrough in lamivudine therapy for chronic hepatitis B

et al. 2008

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“…Lamivudine has demonstrated efficacy and long-term safety and was shown to result in histologic improvement when administered for up to 3 years [16,18,19]. However, resistance to lamivudine emerges at a rate of approximately 20% per year and is found in approximately 70% of patients after 4 years of therapy [20,21]. The emergence of lamivudine resistance may be associated with increases in HBV DNA and alanine aminotransferase (ALT) levels, and loss of histologic response [16,18,22].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

et al. 2010

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Purpose Lamivudine treatment of chronic hepatitis B (CHB) is associated with frequent resistance and loss of clinical benefit. We present outcomes of lamivudinerefractory Japanese patients treated with entecavir for 3 years. Methods Eighty-two patients refractory to lamivudine therapy received entecavir 0.5 or 1 mg daily for 52 weeks in phase II study ETV-052, directly entered rollover study ETV-060, and received entecavir 1 mg daily. Responses were evaluated among patients with available samples.Results After 96 weeks in ETV-060 (148 weeks total entecavir treatment time), 55% (36/65) of patients had hepatitis B virus (HBV) DNA of [400 copies/mL, 85% (52/61) had alanine aminotransferase (ALT) of C1 9 upper limit of normal (ULN), and 14.6% (7/48) achieved HBe seroconversion. A subset of 42 patients received entecavir 1 mg from phase II baseline through 148 weeks: 54% (19/35) had HBV DNA of [400 copies/mL, 84% (27/32) had ALT of C1 9 ULN, and 15% (4/27) achieved HBe seroconversion. Sixteen patients in the 1-mg subset had baseline and week 148 evaluable biopsy pairs: 81% (13/16) showed histologic improvement and 38% (6/16) showed 123Hepatol Int (2010) 4:414-422 DOI 10.1007/s12072-009-9162-x improvement in fibrosis. Genotypic resistance to entecavir emerged in 31 patients for a 3-year cumulative resistance probability of 35.9%. Entecavir was generally well tolerated during ETV-060, with no on-treatment ALT flares. Conclusions Long-term entecavir treatment of lamivudine-refractory CHB resulted in virologic suppression, ALT normalization, and improvements in liver histology. Resistance was consistent with that observed in worldwide studies.

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“…Although efficacious and well tolerated, lamivudine therapy is associated with a high rate of viral resistance [6][7][8][9] that may reach up to 70% after 4 years of treatment [6,10,11]. While some studies have suggested that continuing lamivudine in the presence of resistance may promote HBeAg seroconversion and maintain lower alanine aminotransferase (ALT) and HBV DNA levels than were present at baseline [11][12][13], accumulated evidence now shows that there is no benefit to continuing lamivudine in this population.…”

Section: Introductionmentioning

confidence: 99%

“…While some studies have suggested that continuing lamivudine in the presence of resistance may promote HBeAg seroconversion and maintain lower alanine aminotransferase (ALT) and HBV DNA levels than were present at baseline [11][12][13], accumulated evidence now shows that there is no benefit to continuing lamivudine in this population. Patients with lamivudine-resistant HBV who continue to receive lamivudine have been shown to experience increases in viral load [6,10,[14][15][16], hepatic flares that may lead to decompensation [15,[17][18][19], and reduction or reversal of histologic improvement [20]. These observations highlight the need for a treatment alternative for chronic hepatitis B patients who have developed lamivudine resistance.…”

Section: Introductionmentioning

confidence: 99%

Entecavir for the treatment of lamivudine-refractory chronic hepatitis B patients in China

Yao

Zhou

et al. 2007

Hepatol Int

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Purpose This randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and safety of entecavir in Chinese patients with lamivudinerefractory chronic hepatitis B.Methods One hundred forty-five lamivudine-refractory patients with chronic hepatitis B were randomized to double-blind treatment with oral entecavir 1 mg (n = 116) or placebo (n = 29) daily for 12 weeks, followed by 36 weeks of open-label entecavir treatment. The primary efficacy endpoint was the mean change from baseline in serum hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR) assay at week 12.Results At week 12, the mean change from baseline in serum HBV DNA by PCR assay was -4.30 log 10 copies/ml for patients on entecavir compared to -0.15 log 10 copies/ ml for patients on placebo (P < .0001). Among patients with baseline serum alanine aminotransferase (ALT) >1 · upper limit of normal (ULN), a higher proportion of entecavir than placebo patients (68% vs. 6%, respectively) achieved ALT normalization by week 12 (P < .0001). After 48 weeks of entecavir treatment, the mean change in HBV DNA by PCR assay was -5.08 log 10 copies/ml, and 85% of patients with baseline ALT >1 · ULN had achieved ALT normalization. The safety profile of entecavir was similar to that of placebo during the first 12 weeks of blinded dosing. Entecavir was also well tolerated during 36 weeks of open-label treatment. Conclusions Lamivudine-refractory chronic hepatitis B patients treated with entecavir demonstrated marked HBV DNA reduction and normalization of ALT in most cases. Entecavir treatment for 48 weeks was well tolerated.

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Four years of lamivudine treatment in Chinese patients with chronic hepatitis B

Abstract: Despite the emergence of YMDD-variant HBV, Chinese patients showed increased HBeAg seroconversion and improvement in ALT levels with an increased duration of treatment with lamivudine.

Cited by 226 publications

References 27 publications

Pretreatment and on-treatment predictors of viral breakthrough in lamivudine therapy for chronic hepatitis B

Pretreatment and on-treatment predictors of viral breakthrough in lamivudine therapy for chronic hepatitis B

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

Entecavir for the treatment of lamivudine-refractory chronic hepatitis B patients in China

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