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HBsAg loss in a New Zealand community study with 28-year follow-up: rates, predictors and long-term outcomes

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Abstract

Background and aims

HBsAg seroclearance is the most desired endpoint in chronic hepatitis B (CHB) but occurs uncommonly. Recent studies have shown baseline HBsAg levels to be predictive of HBsAg loss up to 10 years. We report the 28-year rates of HBsAg loss and outcomes in the Kawerau study cohort from New Zealand, and assess the predictive value of baseline HBsAg levels to predict long-term HBsAg loss.

Methods

The 1984 Kawerau community study identified 572 CHB patients, followed up for 28 years (41 % HBeAg-positive, median age 17 years, range 1–71 years). In 2012, surviving individuals attended a local clinic for an interview, blood tests and transient elastography.

Results

384/218 (74 %) surviving individuals attended the clinic in 2012. Spontaneous HBsAg loss occurred in 145 (33 %) after 12,702 person-years of follow-up (1.14 per 100 person-years). Liver stiffness measurements were significantly lower if HBsAg loss occurred <50 years (mean 6.1 kPa) versus >50 years (mean 11.6 kPa), p = 0.0002. No HCC occurred following HBsAg loss (median follow-up 72 months). Predictors of HBsAg loss were older age and lower baseline HBsAg level (HR for HBsAg loss at 28 years 2.7 (95 % CI 1.7–4.2), 6.7 (95 % CI 3.9–11.4) and 9.4 (95 % CI 5.2–16.9), respectively, for HBsAg 1000–9999, 100–999 and <100 IU/mL compared to HBsAg >10,000 IU/mL at baseline, (p < 0.0001). Baseline HBsAg was a superior predictor of HBsAg loss compared to HBV DNA at all time-points: AUROC at 15 years: 0.87 (95 % CI 0.82–0.93) versus 0.73 (95 % CI 0.66–0.80) (p < 0.0001) and AUROC at 28 years: 0.74 (95 % CI 0.69–0.79) versus 0.67 (95 % CI 0.62–0.72) (p = 0.0007). The optimal cut-off HBsAg level to predict HBsAg seroclearance at 28 years is HBsAg <10,000 IU/mL (sensitivity 72 %, specificity 64 %, NPV 88 %).

Conclusions

Rates of HBsAg loss in our community cohort were high, and occurred earlier than previously reported. Earlier HBsAg loss was associated with less severe liver fibrosis. Baseline HBsAg level was a good predictor of long-term HBsAg loss up to 28 years and superior to HBV DNA.

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Acknowledgements

Helen Purcell of The Hepatitis Foundation of New Zealand.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand

    Tien Huey Lim

  2. New Zealand Liver Transplant Unit, Auckland City Hospital, Private Bag 92024, Auckland, New Zealand

    Edward Gane

  3. The Hepatitis Foundation of New Zealand, Whakatane, New Zealand

    Chris Moyes

  4. Centre for Public Health Research, Massey University, Wellington, New Zealand

    Barry Borman

  5. Research Centre for Māori Health and Development, Massey University, Wellington, New Zealand

    Chris Cunningham

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Correspondence to Tien Huey Lim.

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Conflict of interest

Tien Huey Lim, Edward Gane, Chris Moyes, Barry Borman and Chris Cunningham declare that they have no conflict of interest.

Ethical approval

The 1984 study was approved by the local ethics committee and funded by the New Zealand Medical Research Council. The current 2012 follow-up study was approved by the Northern Y ethics committee and funded by the Health Research Council of New Zealand.

Informed consent

All procedures followed were in accordance with the ethical standards of the Northern Y ethics committee and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study.

Financial support

This study is funded by the Health Research Council of New Zealand and the New Zealand Society of Gastroenterology who do not have any role in the study design, collection, analysis or interpretation of data.

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Lim, T.H., Gane, E., Moyes, C. et al. HBsAg loss in a New Zealand community study with 28-year follow-up: rates, predictors and long-term outcomes. Hepatol Int 10, 829–837 (2016). https://doi.org/10.1007/s12072-016-9709-6

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  • DOI: https://doi.org/10.1007/s12072-016-9709-6

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