Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea

Song, Byung–Cheol; Suh, Dong Jin; Lee, Han Chu; Chung, Young‐Hwa; Lee, Yung Sang

doi:10.1053/jhep.2000.16665

Cited by 309 publications

(297 citation statements)

References 24 publications

(50 reference statements)

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“…Whether lamivudine can be discontinued in patients who have completed 1 year of treatment and have sustained HBeAg loss but no detectable anti-HBe remains to be determined. Based on data from the Korean study, 201 it is not advisable to discontinue treatment before 1 year in patients who have early HBeAg seroconversion.…”

Section: Hbsag-positive Clinical Cirrhosismentioning

confidence: 99%

Chronic hepatitis B

2001

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PREAMBLEThese guidelines have been written to assist physicians and other health care providers in the recognition, diagnosis, and management of patients chronically infected with the hepatitis B virus (HBV). They are intended to suggest preferable approaches to the clinical management of chronic hepatitis B. The recommendations are flexible and are not intended as the only acceptable approach to management and treatment. As the appropriate course of treatment will vary in light of the relevant facts and circumstances surrounding each individual patient with chronic hepatitis B, guidelines are not intended to define the applicable standard of medical care and may be updated periodically as new information becomes available.These guidelines were developed under the auspices of, and approved by, the Practice Guidelines Committee of the American Association for the Study of Liver Diseases. They should be taken as guidelines and not "standards of care." Data used to support the recommendations made were obtained by a literature search of peer-reviewed articles concerning the natural history, diagnosis, and treatment of chronic hepatitis B. In addition, the proceedings of a recent National Institutes of Health workshop on the "Management of Hepatitis B" were considered in the development of these guidelines. 1 The strength of each recommendation is categorized based on the quality of evidence in the literature according to the rating system indicated in Table 1. 2

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Section: Hbsag-positive Clinical Cirrhosismentioning

confidence: 99%

Chronic hepatitis B

2001

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“…Week 24 HBV-DNA level during NA therapy is also predictive of HBeAg seroconversion [22,48]. In addition, a retrospective analysis of HBeAg seroconversion involving 98 HBeAg-positive patients with genotype C CHB who were treated with lamivudine, the cumulative relapse rates at 1 and 2 years post-treatment were 37.5 and 49.2%, respectively, and most relapses were accompanied by an elevation in ALT levels (94%) and reappearance of HBeAg (81%) [50]. More recently, higher rates of HBeAg seroconversion (20-25%) have been reported in clinical trials of newer oral Adapted from Lin et al [14] Hepatol…”

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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“…[7][8][9] The discrepancy between Oriental and Western patients is unknown. However, additional lamivudine treatment after HBeAg seroconversion, 7 serum HBV DNA at the time of HBeAg seroconversion, 8 and age 9 have been reported to be factors for durability. Obviously, these inconsistent results need further studies to clarify the discrepancy.…”

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confidence: 99%

Determinants for Sustained Hbeag Response to Lamivudine Therapy

Chien¹

2003

Hepatology

193

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There are inconsistent data on the durability of hepatitis B e antigen (HBeAg) seroconversion after lamivudine is discontinued. The aim of this study was to examine the determinants for sustained HBeAg response to lamivudine therapy. Both host and viral factors as well as the drug factor were compared between 43 patients with sustained HBeAg response and 39 patients whose response was not sustained. All of them received a mean period of 16 months (range, 3-55 months) lamivudine therapy and had achieved complete response (HBeAg seroconversion plus HBV DNA seroclearance by hybrid capture assay and normal alanine aminotransferase [ALT]) and were followed-up for a mean period of 44 months (range, 12-88 months). Stepwise logistic regression model was used to estimate the sustained response on the presence of the following variables: age; gender; pretherapy ALT; total bilirubin and HBV DNA levels; time to HBeAg seroconversion; additional lamivudine treatment after HBeAg seroconversion; total duration of treatment; hepatitis activity index scores; periportal, intralobular, and portal inflammation and fibrosis scores; scores excluding fibrosis; status of precore mutation; basal core promoter mutation; and genotype. The results showed that genotype (OR, 5.922; 95% CI, 1.611-21.768; P ‫؍‬ .007), age (OR, 0.943; 95% CI, 0.891-0.997; P ‫؍‬ .040), and additional treatment (OR, 1.097; 95% CI, 1.028-1.171; P ‫؍‬ .005) were independent factors to sustained HBeAg response. Further categorical analysis disclosed that patients with genotype B, age <36 years, and additional lamivudine treatment over 8 months have higher sustained response. In conclusion, HBV genotype, age, and additional treatment are the major determinants for the sustained HBeAg response to lamivudine therapy. (HEPATOLOGY 2003;38:1267-1273 L amivudine is a nucleoside analogue with rapid and potent inhibitory effects on hepatitis B virus (HBV) polymerase/reverse transcriptase activity. 1 Previous studies have shown that both Asian and white patients with a pretherapy alanine aminotransferase (ALT) level over 5-fold the upper limit of normal have a higher hepatitis B e antigen (HBeAg) seroconversion rate (ϳ64%) after 1-year lamivudine therapy. 2,3 Although HBV suppression during lamivudine therapy may reduce hepatic inflammation even in the absence of HBeAg seroconversion, 4 HBeAg seroconversion has been accepted as an important indicator of response and has been considered a critical step to ensure sustained HBV suppression. 5 Most of the published studies have shown that full HBeAg seroconversion response was durable in the Western patients (77% [30/39] after a median of 36.6 months). 6 However, it was not durable in Oriental countries such as Korea (62% [20/32] at 1 year; 50% [16/32] at 2 years) and Taiwan (69% at 24 weeks, 55% at 48 weeks, and 44% at 72 weeks). [7][8][9] The discrepancy between Oriental and Western patients is unknown. However, additional lamivudine treatment after HBeAg seroconversion, 7 serum HBV DNA at the time of HBeAg seroconversion, 8 ...

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Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea

Cited by 309 publications

References 24 publications

Chronic hepatitis B

Chronic hepatitis B

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

Determinants for Sustained Hbeag Response to Lamivudine Therapy

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