Determinants for sustained HBeAg response to lamivudine therapy

Chien, Rong‐Nan

doi:10.1053/jhep.2003.50458

Cited by 193 publications

(203 citation statements)

References 30 publications

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“…These data imply that HBV genotype may have no substantial impact on the response to lamivudine treatment. However, Chien et al reported that the sustained response rate to lamivudine was much higher in patients with genotype B than those with genotype C [123]. As to the emergence of drug resistance to lamivudine after prolonged therapy, we found that the development of lamivudine resistance was similar between genotypes B and C [119].…”

Section: Genotypesmentioning

confidence: 46%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host interactions, the natural history of HBV carriers who are infected in early life can be divided into four dynamic phases. The frequency, extent, and severity of hepatitis flares or acute exacerbation in the second immune clearance and/or fourth reactivation phase predict liver disease progression in HBV carriers. In the past decade, hepatitis B viral factors including serum HBV DNA level, genotype, and naturally occurring mutants predictive of clinical outcomes have been identified. The higher the serum HBV DNA level after the immune clearance phase, the higher the incidence of adverse outcomes over time. In addition, high viral load, genotype C, basal core promoter mutation, and pre-S deletion correlate with increased risk of cirrhosis and HCC development. As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. In conclusion, serum HBV DNA level, genotype, and naturally occurring mutants are identified to influence liver disease progression and therapy of chronic hepatitis B. More investigations are needed to clarify the molecular mechanisms of the viral factors involved in the pathogenesis of each stage of liver disease and the response to antiviral treatments.

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Section: Genotypesmentioning

confidence: 46%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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“…In our study, patients infected with genotype C achieved HBeAg seroconversion just as well as those infected with genotype B (32% vs. 30%, respectively). This is in contrast to CHB patients treated with lamivudine, where a higher sustained response has been previously noted in patients infected with genotype B (61%) than genotype C (25%, P = 0.009) [35]. This has particular importance for treating Asian patients, since genotype C was reported to have a high prevalence in studies of Korean patients and was associated with a lack of durability of HBeAg seroconversion [36,37].…”

Section: Discussionmentioning

confidence: 72%

Sustained response to peginterferon alfa-2a (40 kD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B

et al. 2008

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Purpose The 2 reported trials investigated the effectiveness of treatment with peginterferon alfa-2a in Asian patients with chronic hepatitis B (CHB). Methods Patients with HBeAg-positive (n = 708) or HBeAg-negative (n = 332) CHB were enrolled in 2 randomized, double blind, placebo-controlled studies.Patients received peginterferon alfa-2a 180 lg once weekly, peginterferon plus lamivudine 100 mg per day, or lamivudine alone for 48 weeks. Patients were followed up at 6 and 12 months posttreatment. Results Peginterferon alfa-2a provided significantly higher rates of HBeAg seroconversion (31%) in HBeAgpositive patients than did lamivudine (19%, P = 0.005) 6 months posttreatment, irrespective of genotype. Of these, 83% achieving seroconversion during treatment or early posttreatment sustained their response at 12 months posttreatment. In patients who seroconverted, 69% maintained HBV DNA suppression at \10,000 copies/ml and alanine aminotrasferase (ALT) normalization. In HBeAg-negative patients, peginterferon produced a significantly higher combined response of HBV DNA at \20,000 copies/ml and ALT normalization (45%) than lamivudine (31%, P = 0.032), irrespective of genotype. Almost 80% of these patients sustained their response at 12 months posttreatment. Conclusions In conclusion, a finite course of peginterferon alfa-2a provides significant and sustained treatment benefit in Asian CHB patients, who have traditionally been regarded as difficult to treat.

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“…The importance of a 6-to 12-month period of consolidation therapy to reduce the risk of relapse after HBeAg seroconversion has been demonstrated in patients with HBeAg-positive CHB [66,67]. In a study that examined determinants for sustained HBeAg responses to lamivudine therapy involving 82 HBeAg-positive CHB patients, an additional 8 months of lamivudine treatment (OR = 1.097; 95% CI = 1.028-1.171; P = 0.005), in addition to genotype B HBV (versus genotype C) and younger age, was an independent factor associated with sustained HBeAg response [66]. Similar findings were reported in a retrospective study that assessed factors predictive of posttreatment relapse after 12 months of lamivudine therapy in 461 Korean patients with CHB, mostly genotype C [67].…”

Section: Socioeconomic Impact Of Hbeag Seroconversion and The Abilitymentioning

confidence: 99%

HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B

2009

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During the natural history of chronic hepatitis B virus (HBV) infection, the loss of serum hepatitis B e antigen (HBeAg) and the development of anti-HBe antibodies (HBeAg seroconversion) mark a transition from the immune-active phase of disease to the inactive carrier state. This review examines the evidence from natural history and cohort studies on the relationship between HBeAg seroconversion and disease progression. The role of HBeAg seroconversion as an important milestone in the management of HBeAg-positive patients with chronic hepatitis B (CHB), as well as the advantages and disadvantages of administering a finite course of therapy for HBeAg-positive CHB, is also discussed. The evidence from natural history and cohort studies indicates that spontaneous or treatment-induced HBeAg seroconversion is associated with lower rates of disease progression to cirrhosis and hepatocellular carcinoma, a potential of hepatitis B surface antigen seroconversion, and improved survival rates. Updated guidelines developed by major liver associations recommend stopping oral therapy for HBeAgpositive patients who achieve sustained HBeAg seroconversion with polymerase chain reaction-undetectable HBV-DNA on two separate occasions for 6 or more months apart, taking into consideration the individual's clinical and virologic response to therapy, as well as the severity of liver disease. Thus, early induction of HBeAg seroconversion with interferon-based therapy or oral nucleos(t)ide analogues has important clinical and socioeconomic implications for the management of CHB.

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Determinants for sustained HBeAg response to lamivudine therapy

Cited by 193 publications

References 30 publications

Role of viral factors in the natural course and therapy of chronic hepatitis B

Role of viral factors in the natural course and therapy of chronic hepatitis B

Sustained response to peginterferon alfa-2a (40 kD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B

HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B

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