Distinct Relapse Rates and Risk Predictors After Discontinuing Tenofovir and Entecavir Therapy

Su, Tung‐Hung; Yang, Hung‐Chih; Tseng, Tai‐Chung; Liou, Jyh–Ming; Liu, Chen–Hua; Chen, Chi‐Ling; Chen, Pei‐Jer; Chen, Ding‐Shinn; Liu, Chun‐Jen; Kao, Jia‐Horng

doi:10.1093/infdis/jix690

Cited by 66 publications

(94 citation statements)

References 36 publications

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“…In addition to HBsAg and HBcrAg, we also found that age, ALT level, and tenofovir use were predictive of clinical relapse, consistent with previous reports . In light of the inverse correlation between age and HBsAg level, a carefully adjusted analysis is mandatory to unmask the independent association .…”

Section: Discussionsupporting

confidence: 90%

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Combining hepatitis B core‐related and surface antigens at end of nucleos(t)ide analogue treatment to predict off‐therapy relapse risk

Hsu

Nguyen

et al. 2018

Aliment Pharmacol Ther

131

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Summary Background There remains an unmet need for convenient biomarkers to assess the risks of discontinuing nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB). Aim To investigate if hepatitis B core‐related antigen (HBcrAg) is an independent of surface antigen (HBsAg) for risk prediction of NA cessation. Methods This prospective multicentre study enrolled 135 CHB patients who stopped entecavir or tenofovir after achieving viral remission for a median of 25.2 months. All patients stopped NA with negative HBeAg and undetectable viral DNA, and were then observed for clinical relapse and HBsAg loss. Predictors including HBsAg and HBcrAg levels were explored using Cox proportional hazard model and weighted to develop a risk score. Results During a median follow‐up of 25.9 months, clinical relapse and HBsAg loss occurred in 66 and eight patients, respectively, with a 5‐year cumulative incidence of 56.1% (95% CI 46.7‐66.0%) and 8.8% (95% CI 4.3‐17.4%), respectively. HBcrAg was an independent relapse predictor, as well as HBsAg, age, ALT and tenofovir use. A score (SCALE‐B) was calculated by the equation of 35*HBsAg (log IU/mL) + 20*HBcrAg (log U/mL) + 2*age (year) + ALT (U/L) + 40 for tenofovir use. The concordance rates for clinical relapse were 0.87, 0.88, 0.87, 0.85 and 0.90 at 1, 2, 3, 4 and 5 years, respectively. Moreover, HBsAg loss occurred exclusively in low‐risk patients predicted by the score. Conclusions Serum HBcrAg and HBsAg levels were independent predictors of off‐NA relapse and can be factored into a risk score to guide treatment cessation in patients with CHB.

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Section: Discussionsupporting

confidence: 90%

“…Besides, distinct features of each regimen should be taken in to account in making the decision of treatment cessation and the policy of off‐NA monitoring. Emerging data suggested that discontinuation of tenofovir as compared with entecavir was associated with a more rapid and potentially more severe clinical relapse …”

Section: Discussionmentioning

confidence: 99%

Combining hepatitis B core‐related and surface antigens at end of nucleos(t)ide analogue treatment to predict off‐therapy relapse risk

Hsu

Nguyen

et al. 2018

Aliment Pharmacol Ther

131

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“…This study echoed the findings of a systematic review of predominantly Asian studies, which showed that the weighted probability of HBsAg seroclearance was only 2% . Several studies have now indicated that the relapse occurs later with entecavir than with TDF; whether this is related to the differences in NAs or ethnic groups warrants further investigation by prospective studies of different ethnicities …”

Section: Discussionsupporting

confidence: 76%

“…This study echoed the findings of a systematic review of predominantly Asian studies, which showed that the weighted probability of HBsAg seroclearance was only 2%. 24 Several studies have now indicated that the relapse occurs later with entecavir than with TDF [25][26][27] ;…”

Section: (165)mentioning

confidence: 99%

The safety of stopping nucleos(t)ide analogue treatment in patients with HBeAg‐negative chronic hepatitis B

Wong

Chan

Yuen

et al. 2019

Liver International

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Background The rates of hepatitis B surface antigen (HBsAg) seroclearance after stopping nucleos(t)ide analogues (NA) in European (19% in 2 years) and Asian (13% in 6 years) patients with chronic hepatitis B (CHB) vary dramatically. We evaluated the incidence of hepatitis flare and HBsAg seroclearance in hepatitis B e antigen (HBeAg)‐negative Chinese CHB patients who had stopped NA. Methods This was a territory‐wide retrospective study in Hong Kong. We identified HBeAg‐negative CHB patients from January 2000 to December 2017 who had stopped NA treatment for more than 3 months. Hepatitis flare was defined as ALT >2×ULN. Results The 1076 patients were predominantly middle‐aged men (mean age 52 years, male 74.8%) when starting NA; they stopped NA after 82 ± 35 months of treatment. At 44.3 ± 24.6 months after stopping NA, 147 (13.6%) patients had hepatitis flare, which led to resumption of NA; whereas 77 (7.2%) patients had flare but did not resume NA. Decompensation occurred in 7/914 (0.8%) patients. A total of 695 (64.6%) patients remained on NA treatment at the last visit. Eleven patients had achieved HBsAg seroclearance (6 of them had hepatitis flare and 1 of these 6 patients achieved HBsAg seroclearance after NA was restarted). Hepatic events developed in 75/695 (10.8%) patients who had NA resumed vs 43/381 (11.3%) patients who did not resume NA (P = .677). Conclusions Hepatitis flare and retreatment were common in HBeAg‐negative CHB patients who stopped NA treatment; whereas HBsAg seroclearance rarely occurred. Stopping NA to achieve functional cure should not be recommended at this moment.

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“…We found the cumulative incidence of lymphoma in patients exposed to anti‐viral therapy was slightly lower than those without therapy. However, the indication, duration, and compliance of anti‐viral therapy vary, and current anti‐viral therapy only suppresses the virus and virus relapse occurs easily after its discontinuation . Patients received hepatoprotectants did not influence the risk of lymphoma in our study; however, the HBV viral load could not be adjusted in our analysis.…”

Section: Discussionmentioning

confidence: 75%

Chronic hepatitis B is associated with an increased risk of B‐cell non‐Hodgkin's lymphoma and multiple myeloma

Liu

Tseng

et al. 2019

Aliment Pharmacol Ther

Self Cite

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Background: Chronic hepatitis B has been linked to lymphoma with contradictory results.Aim: To investigate the association between chronic hepatitis B and lymphoma by using a nationwide population-based cohort. Methods: Records of patients diagnosed with chronic hepatitis B (hepatitis B virus[HBV] cohort) or without (non-HBV cohort) during 2004-2007 were retrieved from the Taiwan National Health Insurance Research Database. Age, sex, comorbidities, and medical visits were matched using propensity scores between both cohorts, and they were followed up longitudinally until 2012 to determine any new lymphoma development.Results: A total of 203 031 patients were included in each cohort with a mean follow-up of 7-9 years. The lymphoma incidence rate was significantly higher in the HBV cohort than in the non-HBV cohort (29.4 vs 15.9 per 100 000 person-years, P < 0.0001). After adjustment for comorbidities and medical visits, HBV infection was found to be an independent risk factor associated with the development of lymphoma (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.76-2.43, P < 0.0001) and non-Hodgkin's lymphoma (HR: 2.18, 95% CI: 1.80-2.65, P < 0.0001); specifically with an increased risk of diffuse large B-cell lymphoma (HR: 2.69, 95% CI: 2.05-3.52, P < 0.0001), other B-cell lymphoma (HR: 3.11, 95% CI:1.89-5.11, P < 0.0001), and also for multiple myeloma (HR: 1.63, 95% CI: 1.10-2.42, P = 0.016). The association was significant even after excluding lymphoma development within the first year (HR: 2.08, 95% CI: 1.75-2.47, P < 0.0001). Conclusions:Chronic hepatitis B is temporally associated with a 2-fold increased risk of lymphoma, particularly with B-cell non-Hodgkin's lymphoma, and also an increased risk for multiple myeloma.

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Distinct Relapse Rates and Risk Predictors After Discontinuing Tenofovir and Entecavir Therapy

Abstract: Discontinuation of tenofovir disoproxil fumarate treatment rather than entecavir treatment is associated with earlier relapse, and NUC-specific posttherapy monitoring is necessary.

Cited by 66 publications

References 36 publications

Combining hepatitis B core‐related and surface antigens at end of nucleos(t)ide analogue treatment to predict off‐therapy relapse risk

Combining hepatitis B core‐related and surface antigens at end of nucleos(t)ide analogue treatment to predict off‐therapy relapse risk

The safety of stopping nucleos(t)ide analogue treatment in patients with HBeAg‐negative chronic hepatitis B

Chronic hepatitis B is associated with an increased risk of B‐cell non‐Hodgkin's lymphoma and multiple myeloma

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