Peginterferon Alfa-2a, Lamivudine, and the Combination for HBeAg-Positive Chronic Hepatitis B

Lau, George; Piratvisuth, Teerha; Luo, K.X.; Marcellin, Patrick; Thongsawat, Satawat; Cooksley, Graham; Gane, Edward; Fried, Michael; Chow, Wan Cheng; Paik, Seung Woon; Chang, Wei‐An; Berg, Thomas; Flisiak, Robert; McCloud, Philip; Pluck, Nigel

doi:10.1056/nejmoa043470

Cited by 1,410 publications

(1,541 citation statements)

References 35 publications

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“…Subsequent follow-up showed that the loss of HBsAg differed according to HBV genotype: 14% for genotype A, 9% for genotype B, 3% for genotype C, and 2% for genotype D (A vs. D: P = 0.006) [112]. In another multicenter phase 3 trial using a standard dose of pegylated IFN-a 2a for 48 weeks, genotype A patients had the highest HBeAg seroconversion rate (50%) but the difference between genotype B and C patients was not significant (30% vs. 31%) [113]. In a recent randomized controlled trial from China, Zhao et al assessed the efficacy of low-dose, 24-week IFN or pegylated IFN treatment as well as factors predicting sustained response in patients with HBeAgpositive chronic hepatitis B [114].…”

Section: Genotypesmentioning

confidence: 96%

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: 96%

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

Kao

2007

Hepatol Int

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“…Immunoreactivity is represented by high levels of ALT, low levels of HBV-DNA and high necroinflammatory activity at histological analysis. High pretreatment ALT levels and low HBV-DNA levels are associated with higher rates of seroconversion with interferon treatment 45,46,48,49 and also associated with responses to PEG-IFN alpha-2a in HBeAg-negative patients; ALT > 5 -fold the upper limit of normality (ULN) was the most important predictor of combined response (ALT normalization, HBV-DNA suppression) in week 24 postreatment. 50 Quantitative HBsAg has recently become an important area of scientific interest.…”

Section: Pretreatment Predictors Of Response To Peg-ifnmentioning

confidence: 99%

“…44 The HBV genotype A, prevalent in Western Europe and America, is also associated with higher rates of response to treatment with interferon. [45][46][47] In Asia and the Pacific regions, genotypes B and C are more prevalent and there is a controversy whether there is any difference regarding their response to interferon. 15,45,46 Based on the results of well-designed studies, patients with good immunoreactivity tend to respond better to interferon.…”

Section: Pretreatment Predictors Of Response To Peg-ifnmentioning

confidence: 99%

Response predictors to treatment with pegylated interferon in chronic hepatitis B

Ferreira

Tenore

2010

Braz J Infect Dis

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The clinical and epidemiological importance of chronic B hepatitis is currently unquestionable as a cause of end-stage liver disease and hepatocellular carcinoma. Recently, predictors of treatment response of this disease have been studied, both before and during the course of medication. Therapy stopping rules have been proposed, which may be useful in patients presenting poor treatment tolerance. This review discusses the treatment response predictors usefulness, with emphasis on ALT, quantitative HBsAg and HBeAg, quantitative HBV-DNA and HBV genotyp

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“…PegIFN-a therapy results in HBeAg seroconversion rates of up to 32% and 48%, respectively, when assessed at weeks 24 and 48 post-treatment [43][44][45][46] and sustained after cessation of therapy in the majority (80-90%) of HBeAgpositive patients [47]. Baseline HBV and ALT levels are predictive factors for HBeAg seroconversion [47].…”

Section: Treatment-induced Hbeag Seroconversion and Disease Progressionmentioning

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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Peginterferon Alfa-2a, Lamivudine, and the Combination for HBeAg-Positive Chronic Hepatitis B

Abstract: In patients with HBeAg-positive chronic hepatitis B, peginterferon alfa-2a offers superior efficacy over lamivudine, on the basis of HBeAg seroconversion, HBV DNA suppression, and HBsAg seroconversion.

Cited by 1,410 publications

References 35 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

Response predictors to treatment with pegylated interferon in chronic hepatitis B

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

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