Comparison of anti-HBe-positive and HBe-antigen-positive chronic hepatitis B in France

Zarski, Jean Pierre; Marcellin, Patrick; Cohard, Marielle; Lutz, Jean Michel; Bouche, Catherine; Rais, Abbès

doi:10.1016/s0168-8278(05)80352-6

Cited by 61 publications

(52 citation statements)

References 17 publications

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“…57 Patients with HBeAg-negative chronic hepatitis B tend to have lower serum HBV DNA levels and are more likely to run a fluctuating course characterized by persistently elevated or fluctuating ALT levels. 57,60,62 Approximately 0.5% of HBsAg carriers will clear HBsAg yearly; most will develop anti-HBs. 43,69,70 However, low levels of HBV DNA detectable only by polymerase chain reaction (PCR) assays can be found in up to half of these persons after disappearance of HBsAg.…”

Section: Terminology and Natural History Of Chronic Hbv Infectionmentioning

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: Terminology and Natural History Of Chronic Hbv Infectionmentioning

confidence: 99%

Chronic hepatitis B

2001

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“…After reviewing the sources of evidence for this guidance, 374, 375 we identified a Health Technology Assessment report for both treatments published in 2006 by Shepherd et al 371 This report included an economic analysis. Shepherd et al 371 sourced cohort data from a published study undertaken by Fattovich et al, 376 which reported a median age and a male-to-female ratio based on 10 published studies for HBeAg-positive chronic HBV [377][378][379][380][381][382][383][384][385][386][387] and four published studies for HBeAg-negative chronic HBV. [388][389][390][391] We employed the same assumptions as those used by Shepherd et al:…”

Section: Cohort Datamentioning

confidence: 99%

Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation

Crossan

Tsochatzis

Longworth

et al. 2015

Health Technology Assessment

151

190

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BackgroundLiver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established.ObjectiveTo assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease.Data sourcesWe searched various databases from 1998 to April 2012, recent conference proceedings and reference lists.MethodsWe included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted.ResultsGiven a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822.LimitationsA substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments.ConclusionsTreating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD.Study registrationThis study is registered as PROSPERO CRD42011001561.FundingThe National Institute for Health Research Health Technology Assessment programme.

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“…12,75,79,83,84 Other patients become aware of their underlying chronic liver disease only as it reaches an advanced stage with complications. 12,85,86 In general, there are no major differences in presentation compared with HBeAgpositive CHB. 12,86,87 During follow-up, 2 main patterns of disease activity are observed: (1) persistently increased serum aminotransferase levels without tendency for spontaneous remission, with an average 3-to 4-fold increase in ALT values (30%-40% of cases) 71,79 and (2) an erratic pattern of ALT changes with frequent flareups of disease activity (45%-65%).…”

Section: Clinical Aspectsmentioning

confidence: 99%

“…12,85,86 In general, there are no major differences in presentation compared with HBeAgpositive CHB. 12,86,87 During follow-up, 2 main patterns of disease activity are observed: (1) persistently increased serum aminotransferase levels without tendency for spontaneous remission, with an average 3-to 4-fold increase in ALT values (30%-40% of cases) 71,79 and (2) an erratic pattern of ALT changes with frequent flareups of disease activity (45%-65%). 71,79 Sometimes flares are severe resembling acute hepatitis B with ALT values exceeding 1,000 IU/L and positive IgM anti-HBc.…”

Section: Clinical Aspectsmentioning

confidence: 99%

Hepatitis B e antigen-negative chronic hepatitis B

2001

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Thirty years ago, the diagnosis of chronic hepatitis B (CHB) was thought to require the presence of hepatitis B e antigen (HBeAg), as a reliable and sensitive marker of hepatitis B virus (HBV) replication. 1 Individuals positive for hepatitis B surface antigen (HBsAg) but negative for HBeAg were considered to have nonreplicative HBV infection, and if their liver enzymes were normal or nearly normal they were referred to as asymptomatic or healthy HBsAg or HBV carriers. 2 If, on the other hand, they displayed elevated serum aminotransferases and liver histology indicative of chronic hepatitis, they were generally thought to be suffering from other superimposed or complicating conditions such as hepatitis D virus infection, alcohol-induced, metabolic, autoimmune, drug-induced, or other forms of chronic liver disease. 3 In the early 1980s it became apparent that HBV could replicate in the absence of HBeAg. [4][5][6] Patients from the Mediterranean area, although negative for HBeAg and positive for antibodies to HBeAg (anti-HBe), were reported to have CHB with replicating HBV. 7 The term anti-HBe-positive or HBeAgnegative CHB was then proposed 4 and subsequently became widely accepted. In 1989 the molecular basis of this form of CHB was discovered 8,9 with the identification of HBV mutations preventing HBeAg formation from an otherwise normally replicating HBV. 10,11 With time, it became apparent that HBeAg-negative CHB, initially viewed as an atypical and rare form of CHB mainly restricted in the Mediterranean area, had a much wider geographical distribution and that its frequency was increasing. 12 Its molecular virology and immunology were found to be more complex than initially thought, 13 whereas the selection of precore HBV mutants was shown to be largely determined by the HBV genotype. 14 Mutations abolishing or diminishing HBeAg formation were identified along with changes in other parts of the HBV genome. 14 More recently, the new nucleoside analog, lamivudine, has been used to treat a sizeable number of patients with HBeAg-negative CHB, and important information on its efficacy and the development of resistance has been collected. [15][16][17][18] DEFINITION AND NOMENCLATUREThe term HBeAg-negative CHB defines the condition as disease caused by strains of HBV that are not producing HBeAg. 12 It does not specify the mutations responsible for the lack of HBeAg, i.e., a precore stop-codon mutation, 10 a double basic core promoter (BCP) mutation, or other, 14 and it says nothing about the level of HBV replication. The alternative term "precore mutant CHB," used by some investigators, also does not specify the nature of the precore mutation. In clinical practice, the term HBeAg-negative CHB is appropriate for patients with chronic HBV infection who test negative for HBeAg, are usually positive for anti-HBe, have increased alanine aminotransferase (ALT) levels and display detectable HBV DNA in serum by classical hybridization techniques. 12 Despite the fact that the identification of the underlying mutations in ...

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Comparison of anti-HBe-positive and HBe-antigen-positive chronic hepatitis B in France

Cited by 61 publications

References 17 publications

Chronic hepatitis B

Chronic hepatitis B

Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation

Hepatitis B e antigen-negative chronic hepatitis B

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