The long-term outcome of interferon-α treated and untreated patients with HBeAg-negative chronic hepatitis B

Papatheodoridis, George; Manesis, Emanuel K.; Hadziyannis, Stephanos J.

doi:10.1016/s0168-8278(00)00094-5

Cited by 269 publications

(261 citation statements)

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“…Such a survival rate was observed in a patient population with 2 baseline factors, old age (mean of 52 years), and frequent (Ͼ30%) presence of cirrhosis, which have been repeatedly shown to be strongly associated with development of liver-related complications and poor survival. 26,28 These data may reflect the results of long-term antiviral therapy in attentive clinical practice, because we included patients from 4 liver centers treated with similar therapeutic strategies, but not according to a strict therapeutic protocol. The efficacy of lamivudine was similar to what has been previously reported in other studies from Greece 16,17 and Italy 29 with approximately one third of patients remaining in remission at 4 years of therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Such a management is associated with outcomes similar to those observed after sustained response to IFN␣, both being significantly better than the outcomes in patients without sustained response after IFN␣ or in untreated cases. 26 In HBeAg-negative CHB patients under long-term lamivudine monotherapy, major liver complications usually develop in the presence of baseline cirrhosis or advanced fibrosis following the emergence of breakthroughs. Thus, in such patients with advanced fibrosis, very close follow-up for lamivudine resistance and prompt onset of effective additional antiviral therapy is required in an effort to reduce the rate of complications, or alternatively the ab initio use of agent(s) with low resistance rates should be considered.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Two other cohorts of HBeAg-negative CHB patients, who constituted the population in another published study, 26 were also evaluated. Two hundred nine IFN␣-treated and 195 untreated patients fulfilled inclusion and exclusion criteria described previously in detail 26 and being similar to the criteria used for the main popu-lation. No patient of these 2 historical cohorts was treated with any nucleos(t)ide agent during the follow-up period of our previous study, 26 which ended in December 1998, when such agents were not approved for the treatment of CHB.…”

Section: Methodsmentioning

confidence: 99%

“…Two hundred nine IFN␣-treated and 195 untreated patients fulfilled inclusion and exclusion criteria described previously in detail 26 and being similar to the criteria used for the main popu-lation. No patient of these 2 historical cohorts was treated with any nucleos(t)ide agent during the follow-up period of our previous study, 26 which ended in December 1998, when such agents were not approved for the treatment of CHB. In IFN␣-treated patients, sustained off-therapy biochemical response was observed in 57 (sustained responders) and biochemical relapse or no response in the remaining 152 cases (non-sustained responders).…”

Section: Methodsmentioning

confidence: 99%

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Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine

et al. 2005

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We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients treated for 3.8 ؎ 1.4 years and 2 historical similar cohorts: 1 treated with interferon-alfa (n ‫؍‬ 209) and 1 untreated (n ‫؍‬ 195). Virological or biochemical remission rate at 48 months under lamivudine was 34% or 36%, respectively, whereas adefovir was administered in 79 patients with virological-biochemical breakthroughs or no response. Of the lamivudinetreated patients, 4 died, 1 underwent a transplantation, and another 8 developed major events, all having advanced fibrosis at baseline and all but 1 having experienced breakthroughs or no response. At 5 years, survival was 96%, and major event-free survival was 93%. The major event-free survival was significantly better in patients with than in those without virological remission under lamivudine. At the end of follow-up, both survival and major event-free survival were independently associated with type of and response to treatment, being significantly better in patients under long-term antiviral therapy or interferon sustained responders than in interferon non-sustained responders or untreated cases (5-year survival: 96% or 98% vs. 88% or 90%, respectively). In conclusion, in HBeAg-negative chronic hepatitis B, long-term nucleos(t)ide analog therapy starting with lamivudine significantly improves survival and reduces the risk of major complications, compared with interferon non-sustained responders or untreated patients. In such patients with advanced fibrosis, close follow-up for lamivudine resistance and prompt onset of additional antiviral therapy is required or the ab initio use of agent(s) with low resistance rates should be considered. (HEPATOLOGY 2005;42:121-129.) H epatitis e antigen (HBeAg)-negative chronic hepatitis B (CHB) represents a rather late phase in the course of chronic hepatitis B virus (HBV) infection 1,2 usually associated with replication of HBV variants that are unable to produce HBeAg because of mutations either at the precore or basic core promoter region of the viral genome. 2,3 HBeAg-negative CHB is a potentially severe and progressive form of chronic liver disease with rare spontaneous remissions, frequent progression to cirrhosis, and increased risk of hepatocellular carcinoma (HCC). [4][5][6][7] The management of CHB has improved over the last years with the addition of lamivudine and more recently adefovir dipivoxil (ADV), but it is still suboptimal in achieving sustained off-therapy responses. [8][9][10][11] In particular in HBeAg-negative CHB, interferon-alfa (IFN␣), the first available effective therapeutic option in CHB, is the agent offering the higher chances for sustained-off therapy response ranging between 18% and 30%. 10-13 Conversely, both lamivudine and ADV, 2 oral, safe, and well-

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine

et al. 2005

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Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults

Chou¹,

Dana²,

Bougatsos³

et al. 2020

JAMA

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ImportanceA 2014 review for the US Preventive Services Task Force (USPSTF) found antiviral therapy for hepatitis B virus (HBV) infection associated with improved intermediate outcomes, although evidence on clinical outcomes was limited.ObjectiveTo update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF.Data SourcesCochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020.Study SelectionRandomized clinical trials (RCTs) on screening and antiviral therapy; cohort studies on screening, antiviral therapy clinical outcomes, and the association between achieving intermediate outcomes after antiviral therapy and clinical outcomes.Data Extraction and SynthesisOne investigator abstracted data; a second investigator checked accuracy. Two investigators independently assessed study quality. Random-effects profile likelihood meta-analysis was performed.ResultsThirty trials and 20 cohort studies, with a total of 94 168 participants, were included. No study directly evaluated the effects of screening for HBV infection vs no screening on clinical outcomes such as mortality, hepatocellular carcinoma, or cirrhosis. Screening strategies that focused on risk factors such as ever having immigrated from high-prevalence countries and demographic and behavioral risk factors would identify nearly all HBV infection cases. In 1 study (n = 21 008), only screening immigrants from high-prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (n = 2972), antiviral therapy compared with placebo or no treatment was associated with greater likelihood of achieving intermediate outcomes, such as virologic suppression and hepatitis B e-antigen (HBeAg) or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virologic suppression to 17 for HBeAg seroconversion. Based on 12 trials (n = 4127), first-line antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (n = 4809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (n = 3893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes but were heterogeneous (hazard ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events vs placebo or no antiviral therapy.Conclusions and RelevanceThere was no direct evidence for the clinical benefits and harms of HBV screening vs no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes.

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