Reduced risk of relapse after long‐term nucleos(t)ide analogue consolidation therapy for chronic hepatitis B

Chi, Heng; Hansen, Bettina E.; Yim, Colina; Arends, Pauline; Abu‐Amara, Mahmoud; Eijk, Annemiek A. van der; Feld, Jordan J.; Knegt, Robert J. de; Wong, David; Janssen, Harry L.A.

doi:10.1111/apt.13150

Cited by 94 publications

(112 citation statements)

References 30 publications

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“…A previous study of HBeAg-negative patients reported a high rate of HBsAg loss of 39% within 6 years after adefovir therapy discontinuation, and 13 (72%) out of 18 patients who achieved a sustained response after stopping adefovir therapy were clear of HBsAg 23 . A recent study found that 9% of the HBeAg-positive patients and 14% of HBeAg-negative patients became HBsAg-negative at 3 years after NA discontinuation 24 . Our study is consistent with these studies 23, 24 .…”

Section: Discussionmentioning

confidence: 99%

“…A recent study found that 9% of the HBeAg-positive patients and 14% of HBeAg-negative patients became HBsAg-negative at 3 years after NA discontinuation 24 . Our study is consistent with these studies 23, 24 . We also found that patients with HBsAg ≤ 50 IU/mL, 51–100 IU/mL, and 101–150 IU/mL had similar rates of HBsAg loss (all more than or near 60% at 72 months).…”

Section: Discussionmentioning

confidence: 99%

“…NAs have potent antiviral activity but do not have a direct immunomodulatory effect. Thus, HBsAg seroclearance is rare during NA treatment even with the most potent NA 24–27 . The host immune mechanisms that are modulated during the long period of HBV suppression by NA treatment react effectively to the resumed HBV replication.…”

Section: Discussionmentioning

confidence: 99%

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Incidence and predictors of HBV relapse after cessation of nucleoside analogues in HBeAg-negative patients with HBsAg ≤ 200 IU/mL

Yao

Hung

et al. 2017

Sci Rep

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The predictors of hepatitis B virus (HBV) relapse and HBsAg loss after cessation of nucleos(t)ide analogues (NA) in HBeAg-negative patients with end-of-treatment HBsAg ≤ 200 IU/mL remains unclear. The study recruited 119 chronic hepatitis B (CHB) patients who achieved end-of-treatment HBsAg ≤ 200 IU/mL, were treated with lamivudine (n = 34) and entecavir (n = 85). The 5-year rates of post-treatment virological relapse, clinical relapse, and HBsAg loss at 60 months were 39.4%, 27.6%, and 45.9%, respectively. Cox regression analysis revealed that HBV DNA at entry and end-of-treatment HBsAg levels were independent predictors of virolgical and clinical relapse. HBV genotype C and end-of-treatment HBsAg were independent factors of HBsAg loss. Patients with a combination of end-of-treatment HBsAg < 50 IU/mL and HBV DNA < 2 × 105 IU/mL at entry experienced the lowest virological and clinical relapse rates (5% and 0% at 60 months, respectively). In contract, patients with a combination of end-of-treatment HBsAg ≥ 50 IU/mL and HBV DNA ≥ 2 × 105 IU/mL at entry experienced high virological and clinical relapse (80.7% and 71.5% at 60 months, respectively). No patients experienced hepatic decompensation when clinical relapse occurred after timely retreatment. A combination of HBV DNA levels at entry and end-of-treatment HBsAg levels was useful for predicting the post-treatment HBV relapse in HBeAg-negative patients with HBsAg ≤ 200 IU/mL.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Incidence and predictors of HBV relapse after cessation of nucleoside analogues in HBeAg-negative patients with HBsAg ≤ 200 IU/mL

Yao

Hung

et al. 2017

Sci Rep

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“…In a systematic review among 733 HBeAg‐positive patients who have stopped NA, the probability of off‐therapy response, defined as sustained HBeAg seroconversion with HBV‐DNA < 20,000 IU/mL, was 62.5% at month 12, 53.4% at month 24, and 51.5% at month 36 . It seems that extension of NA consolidation to up to 3 years post‐HBeAg seroconversion can increase the chance of sustainability of off‐treatment response …”

Section: The Decision To Stop Nucleos(t)ide Analogmentioning

confidence: 99%

Okuda lecture: Challenges of hepatitis B in the era of antiviral therapy

Chan

2018

J of Gastro and Hepatol

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Nucleos(t)ide analogs (NAs) are effective, safe, and convenient antiviral therapy to suppress replication of hepatitis B virus, which can be translated into improved long‐term outcome of chronic hepatitis B patients. The current recommended first‐line NAs, namely, entecavir and tenofovir, are largely free from problems of drug resistance. Nonetheless, there are still a few challenges in the era of NA. First, the risk of hepatocellular carcinoma can only be reduced but not eliminated, particularly among cirrhotic patients. For cirrhotic patients who have persistent low‐level viremia on NA, that is, partial responders, the risk of hepatocellular carcinoma is higher than those with complete viral suppression. The best strategy to manage partial responders to entecavir or tenofovir is uncertain. Second, immune‐tolerant patients are very difficult to treat with NA. A significant proportion of immune‐tolerant patients will have detectable viremia despite a few years of continuous NA treatment, and the rate of hepatitis B e‐antigen seroconversion is very low. Third, most patients need long‐term treatment as NA cannot eliminate covalently closed circular DNA in the hepatocytes. Some patients can consider stop NA according to treatment guidelines, but viral and clinical relapses often occur after treatment cessation. There is no concrete consensus on when one should stop NA in a hepatitis B e‐antigen‐negative patient among different treatment guidelines. New biomarkers such as hepatitis B surface antigen level can be used to select patients to stop NA, but the data are still preliminary.

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“…Consolidation therapy of at least three years decreased the rate of relapse and increased the rate of HBsAg loss significantly. [5]…”

Section: Introductionmentioning

confidence: 99%

HBsAg clearance in chronic hepatitis B patients with add-on pegylated interferon alfa-2a to ongoing tenofovir treatment: A randomized controlled study

Ashgar

Peedikayil

Quaiz

et al. 2017

Saudi J Gastroenterol

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Reduced risk of relapse after long‐term nucleos(t)ide analogue consolidation therapy for chronic hepatitis B

Abstract: SUMMARY BackgroundBefore stopping nucleos(t)ide analogue (NA) treatment in chronic hepatitis B (CHB), 6-12 months of consolidation therapy is recommended.

Cited by 94 publications

References 30 publications

Incidence and predictors of HBV relapse after cessation of nucleoside analogues in HBeAg-negative patients with HBsAg ≤ 200 IU/mL

Incidence and predictors of HBV relapse after cessation of nucleoside analogues in HBeAg-negative patients with HBsAg ≤ 200 IU/mL

Okuda lecture: Challenges of hepatitis B in the era of antiviral therapy

HBsAg clearance in chronic hepatitis B patients with add-on pegylated interferon alfa-2a to ongoing tenofovir treatment: A randomized controlled study

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