Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic Hepatitis B Virus Infection: Systematic Review and Meta-analysis

Anderson, Ryan T.; Choi, Hannah; Lenz, Oliver; Peters, Marion G.; Janssen, Harry L.A.; Mishra, Poonam; Donaldson, Eric F.; Westman, Gabriel; Buchholz, Stephanie; Miller, Veronica; Hansen, Bettina E.

doi:10.1016/j.cgh.2020.05.041

Cited by 88 publications

(78 citation statements)

References 45 publications

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“…Recently, there has been interest in functional cure of CHB, defined as loss of hepatitis B virus surface antigen (HBsAg) 24 weeks after end of therapy 3 . These have significantly improved clinical outcomes such as better survival, reduced HCC and liver‐related mortality 4 . Current widely prescribed therapies such as nucleos(t)ide analogues (NAs) and immunomodulators (pegylated interferon) are limited in their ability to achieve functional cure.…”

Section: Introductionmentioning

confidence: 99%

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)

Lim

Phyo

Ling

et al. 2020

Aliment Pharmacol Ther

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SummaryBackgroundBiomarkers such as quantitative HBsAg (qHBsAg), quantitative hepatitis B virus (HBV) core‐related antigen (qHBcrAg) and HBV RNA may be useful in predicting HBsAg loss in patients with chronic hepatitis B (CHB) undergoing antiviral therapy.Aim(s)Our study evaluated qHBsAg, HBV RNA and qHBcrAg as a posthoc analysis of a randomized clinical trial of peginterferon±NA to determine their utility in predicting HBsAg loss.MethodsCHB patients who completed therapy with 48weeks peginterferon alpha2b ± nucleoside analogue therapy (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBsAg loss. The predictive ability of qHBsAg, qHBcrAg, HBV RNA and other variables were investigated by univariate and multivariate logistic models for HBeAg‐negative patients by odds ratios, area under the curve (AUC), sensitivity, specificity, and positive and negative likelihood ratios (LR).ResultsHBsAg loss occurred in 15/114(13%) HBeAg‐negative CHB patients who completed 48 weeks of peginterferon. At baseline, qHBsAg was superior to HBcrAg and HBV RNA with AUC 0.916, 0.649 and 0.542, respectively. Using multivariate analysis, the model comprising treatmentarm, age, gender, baseline qHBsAg, HBcrAg and HBV RNA, weeks 4 & 8 qHBsAg had the highest AUC(0.98), but the univariate model with week 8 qHBsAg <70 IU/mL had AUC 0.96. Hence, the contributions of variables other than qHBsAg were marginal. HBV RNA and qHBcrAg were weak predictors of HBsAg loss. Kinetics of the novel markers showed only qHBsAg had a good relationship with HBsAg loss while HBV RNA had a marginal relationship and HBcrAg did not change at all, and none had a good relationship with viral rebound.ConclusionsOn‐treatment biomarker predictors were better than baseline ones, and the best predictor of HBsAg loss at 72 weeks was week 8 qHBsAg <70 IU/mL.

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Section: Introductionmentioning

confidence: 99%

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)

Lim

Phyo

Ling

et al. 2020

Aliment Pharmacol Ther

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“…One meta-analysis of 34 published studies estimated the pooled annual rate to be 1% with a cumulative 5-year rate of 4% with a higher likelihood of clearance noted in those with lower HBV DNA levels or with HBe antigen negative status at baseline [54]. Additional strategies are needed to achieve higher and more consistent rates of functional cure in persons with chronic HBV with or without HIV as HBsAg loss has been shown to be associated with improved clinical outcomes [53,55]. Chronic HBV poses a variety of challenges to reaching this goal apart from HBV DNA integration.…”

Section: Management Issues: Functional Cure Fibrosis Assessment Andmentioning

confidence: 99%

Chronic Hepatitis B and HIV Coinfection: a Continuing Challenge in the Era of Antiretroviral Therapy

Kim

2020

Curr Hepatology Rep

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Purpose of Review The burden of chronic hepatitis B (HBV) remains disproportionately high among people living with HIV (PLWH) despite the advent of HBV vaccination and HBV-active antiretroviral therapy (ART). This review summarizes new insights and evolving issues in HIV-HBV coinfection. Recent Findings HBV-HIV coinfection is still a leading cause of cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality more than a decade after the approval of tenofovir. While tenofovir-based ART has been shown to improve rates of HBV virologic suppression and halt fibrosis progression, the long-term benefits on the prevention of end-stage liver disease or HCC in HIV-HBV coinfection have yet to be convincingly demonstrated in PLWH. Missed opportunities for HBV vaccination persist despite evidence of ongoing risk for HBV infection in this population. Summary Even as we work towards HBV elimination and functional cure, ongoing efforts should focus on optimizing risk stratification as well as uptake of HBV-active antiviral therapy and HBV immunization in this priority population.

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“…course and minimal risk of HCC development subsequently. [4][5][6] Also, HBsAg seroclearance is associated with a further reduction of HCC risk among CHB patients who achieved complete HBV DNA suppression under NA treatment. 7 While a complete HBV eradication from the host, that is, sterilising cure, is unlikely to be feasible in the near future, 8 HBsAg seroclearance is a more achievable goal and an optimal treatment endpoint of NA treatment for CHB patients as recommended by the international clinical guidelines.…”

Section: Ifn Chb Patients Who Lost Hbsag Usually Have a Favourable Cmentioning

confidence: 99%

“…It can be achieved spontaneously or induced by NA or (PEG)‐IFN. CHB patients who lost HBsAg usually have a favourable clinical course and minimal risk of HCC development subsequently 4‐6 . Also, HBsAg seroclearance is associated with a further reduction of HCC risk among CHB patients who achieved complete HBV DNA suppression under NA treatment 7 .…”

Section: Introductionmentioning

confidence: 99%

Similarly low risk of hepatocellular carcinoma after either spontaneous or nucleos(t)ide analogue‐induced hepatitis B surface antigen loss

Yip

Wong

Tse

et al. 2020

Aliment Pharmacol Ther

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SummaryBackgroundIt is unknown whether patients with chronic hepatitis B (CHB) who achieved hepatitis B surface antigen (HBsAg) seroclearance spontaneously or following anti‐viral therapy have similar clinical outcomes.AimTo compare the risk of hepatocellular carcinoma (HCC) in patients with CHB who either cleared HBsAg spontaneously or following anti‐viral therapyMethodsAdult CHB‐monoinfected patients who cleared HBsAg between January 2000 and March 2019 were identified from a territory‐wide database in Hong Kong. Patients with liver transplantation and/or HCC before HBsAg loss were excluded. Patients’ demographics, comorbidities, anti‐viral treatment, laboratory parameters and HCC development were analysed.ResultsOf 7,124 identified patients with CHB who cleared HBsAg, mean age was 58.1 ± 13.8 years; 4,340 (60.9%) were male; 451 (6.3%) had cirrhosis; 5,917 (83.1%) and 1,207 (16.9%) had spontaneous and nucleos(t)ide analogue (NA)‐induced HBsAg seroclearance, respectively. Most patients had normal liver function at HBsAg loss. Patients with NA‐induced HBsAg seroclearance were younger, and more likely to be male and cirrhotic than patients with spontaneous HBsAg loss. At a median (interquartile range) follow‐up of 4.3 (2.2‐7.6) years, 97 (1.6%) and 16 (1.3%) patients with spontaneous and NA‐induced HBsAg loss developed HCC, respectively. Patients who achieved NA‐induced HBsAg loss had comparable HCC risk as those with spontaneous HBsAg loss (adjusted subdistribution hazard ratio 0.75, 95% CI 0.43‐1.32, P = 0.323). The results remained robust in propensity score weighting and matching analyses.ConclusionThe HCC risk was similarly low after either spontaneous or NA‐induced HBsAg seroclearance in a territory‐wide cohort of patients with CHB who had cleared HBsAg.

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Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic Hepatitis B Virus Infection: Systematic Review and Meta-analysis

Cited by 88 publications

References 45 publications

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)

Chronic Hepatitis B and HIV Coinfection: a Continuing Challenge in the Era of Antiretroviral Therapy

Similarly low risk of hepatocellular carcinoma after either spontaneous or nucleos(t)ide analogue‐induced hepatitis B surface antigen loss

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