title: HBsAg loss in a New Zealand community study with 28-year follow-up: rates, predictors and long-term outcomes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand. tienhuey@gmail.com.
authors.forename: Tien Huey
authors.initials: TH
authors.lastname: Lim
authors.affiliation: New Zealand Liver Transplant Unit, Auckland City Hospital, Private Bag 92024, Auckland, New Zealand.
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.affiliation: The Hepatitis Foundation of New Zealand, Whakatane, New Zealand.
authors.forename: Chris
authors.initials: C
authors.lastname: Moyes
authors.affiliation: Centre for Public Health Research, Massey University, Wellington, New Zealand.
authors.forename: Barry
authors.initials: B
authors.lastname: Borman
authors.affiliation: Research Centre for Māori Health and Development, Massey University, Wellington, New Zealand.
authors.forename: Chris
authors.initials: C
authors.lastname: Cunningham
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D054459:Elasticity Imaging Techniques; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D011237:Predictive Value of Tests; D011379:Prognosis; D055815:Young Adult
chemical_list: D006513:Hepatitis B e Antigens
keywords: Baseline HBsAg level; HBsAg loss; Hepatocellular carcinoma; Seroconversion