Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone: Results of a pilot study

Serfaty, Lawrence; Thabut, Dominique; Zoulim, Fabien; Andréani, Tony; Chazouillères, Olivier; Carbonell, Nicolas; Loria, Alain; Poupon, Raoul

doi:10.1053/jhep.2001.26819

Cited by 77 publications

(58 citation statements)

References 31 publications

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“…We assumed that not only HBeAg/anti-HBe status, HBV-DNA, and ALT levels but also a change in the nucleotide sequence in the precore region of HBV-DNA may serve in the decision making for the appropriate timing of the cessation of lamivudine treatment. No drastic advantage was seen in the combination therapy of both lamivudine and IFN, in comparison with lamivudine monotherapy [Schalm et al, 2000;Serfaty et al, 2001;Tatulli et al, 2001]. However, in these studies, the emergence of lamivudineresistant mutants was nil or rare.…”

Section: Discussionmentioning

confidence: 86%

Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy

Kuwahara

Kumashiro

Murashima

et al. 2003

Journal of Medical Virology

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It has been reported that spontaneous or interferon (IFN)-induced hepatitis B e (HBe) seroconversion has usually been associated with the development of a stop codon in the precore region. However, the difference between lamivudine-induced seroconversion and spontaneous or IFN-induced seroconversion is not known. The aim of this study was to investigate the correlation between the evolution of the precore and core promoter mutations and lamivudine-induced seroconversion. Forty-five patients with chronic hepatitis B virus (HBV) infection who were treated with lamivudine for more than 1 year were enrolled. The nucleotide sequence of the precore and core promoter region was determined before and after treatment with lamivudine for 1 year. Among 29 patients who were hepatitis B e antigen (HBeAg)-positive before treatment, 12 (41.3%) lost HBeAg during the course of treatment for 1 year. Of these, eight patients (66.7%) still had precore wild type HBV after 1 year. After 1 year, reversion to precore wild type HBV was detected in 11 (64.7%) of 17 patients who had precore mutant HBV before treatment. Twelve (70.6%) of 17 patients who were persistently HBeAg-positive had precore wild type HBV before and after treatment for 1 year. Despite the loss of HBeAg, two thirds of the patients still had precore wild type HBV after the 1-year treatment. It is suggested that lamivudine-induced seroconversion differs from spontaneous or IFN-induced seroconversion in the change of nucleotides in the precore region. The reversion in the precore region may be caused by the difference of drug-susceptibility to lamivudine. The antiviral effect of lamivudine may be more effective in the precore mutant HBV than in the precore wild type HBV.

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Section: Discussionmentioning

confidence: 86%

Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy

Kuwahara

Kumashiro

Murashima

et al. 2003

Journal of Medical Virology

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“…8,9 The present case highlights the possibility of hepatitis B associated MN in children presenting with nephrotic syndrome and the possible harm by initiating steroids without confirming HBsAg status. It is recommended that hepatitis B serology should be part of the initial screen in all children presenting with nephrotic syndrome, especially those from endemic areas where hepatitis B is prevalent.…”

Section: Discussionmentioning

confidence: 81%

Steroid resistant nephrotic syndrome in a child with chronic hepatitis B infection

Dhingra¹,

Kanitkar²,

Sengupta

2012

Medical Journal Armed Forces India

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We present a case of SRNS in a 5-yr-old boy who had received 3 weeks of daily steroids before referral to our hospital. At presentation the child had urinary tract infection (UTI) which was adequately treated. The child had persistence of proteinuria, even after completing 4 weeks of daily steroids in adequate dose. Secondary causes of nephrotic syndrome were looked for which revealed presence of chronic HBV infection in the patient with a very high viral load. Kidney biopsy was characteristic of MN with predominant IgG,

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“…They find that, when compared with pegylated IFN-α monotherapy, lamivudine given 4 wk before 24 wk of pegylated IFN-α treatment was associated with a better sustained response with a higher proportion of patients with undetectable HBV DNA levels and sustained HBeAg loss 24 wk after off-treatment, though these differences were not shown at the end of treatment. Serfaty and his colleagues also show similar findings, that pretreatment with 20 wk of lamivudine before IFN-α is associated with a better-sustained virologic response (14). Pretreatment HBV DNA level has been shown to an important predictive factor for treatment response with IFN-α.…”

mentioning

confidence: 67%

Combination Therapy for Chronic Hepatitis B: Simultaneous or Sequential?

Yuen¹,

Lai²

2007

Am J Gastroenterol

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Various regimens of combination or sequential therapy using nucleoside/nucleotide analogues (NAs) and interferon-alfa (IFN-α) have been tried for the treatment of chronic hepatitis B. To date, combination therapy of two NAs and of IFN-α and NAs fails to achieve extra viral suppression. Sequential therapy with lamivudine followed by IFN-α seems to have better sustained virologic response. However, the long-term beneficial effect of using this approach remains to be defined. (Am J Gastroenterol 2007;102:105-106) Unlike the treatment of chronic hepatitis C, total eradication of the hepatitis B virus (HBV) is still elusive. There are two groups of agents for the treatment of chronic hepatitis B (CHB): nucleoside/nucleotide analogues (NAs) and interferon-alfa (IFN-α). Many studies have been performed to determine whether combination of various drugs for CHB can; (a) synergistically increase the efficacy; (b) minimize side effects; and (c) reduce the rate of emergence of drugresistant mutations. One can combine two or three NAs, or IFN-α (conventional or pegylated) with NAs.Disappointingly, nearly all trials with different combinations of NAs show no added advantage in HBV DNA reduction compared to that achieved by the more potent of the two agents used alone (1-3). The chance of emergence of drug-resistant mutations is reduced with some of these combinations, especially if the study is extended beyond 1 yr.Combining IFN-α with NAs seems to be a logical approach alternative, because IFN-α and NAs act through different mechanisms for the control of CHB. There are two differing strategic plans for such combination. First, combination of IFN-α and lamivudine is given to patients at the same time. Secondly, lamivudine is given to patients several weeks before the administration of IFN-α.In the studies using lamivudine and IFN-α simultaneously, the IFN-α treatment is usually given for 16-24 wk or 48-52 wk. However, the lamivudine is also given for only 48-52 wk and then stopped. These trials consistently show that there is no difference observed in the HBV DNA reduction between combination therapy and lamivudine or IFN-α monotherapy after 6 months of cessation of treatment (4-7). Some trials, however, show that addition of IFN-α reduces the chance of emergence of lamivudine-resistant mutations (8,9). This advantage may not be of great significance, because the newer NAs such as adefovir and entecavir are associated with a much lower rate of drug-resistant mutations. However, the major fault in the design of all these trials that renders their results of dubious significance is that lamivudine is stopped after 1 yr of therapy. In the first place, this is not consistent with the usual clinical practice in the use of NAs, it being well established that for durable response, NAs should not be stopped until 6-12 months after stable HBeAg seroconversion for HBeAg-positive patients and should be maintained on a long-term basis for HBeAg-negative patients. In the second place, at the end of combination therapy with lamivudine a...

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Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone: Results of a pilot study

Cited by 77 publications

References 31 publications

Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy

Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy

Steroid resistant nephrotic syndrome in a child with chronic hepatitis B infection

Combination Therapy for Chronic Hepatitis B: Simultaneous or Sequential?

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