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

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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 10years. 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. The 1984 Kawerau community study identified 572 CHB patients, followed up for 28years (41% HBeAg-positive, median age 17years, range 1-71years). In 2012, surviving individuals attended a local clinic for an interview, blood tests and transient elastography. 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<50years (mean 6.1kPa) versus>50years (mean 11.6kPa), p=0.0002. No HCC occurred following HBsAg loss (median follow-up 72months). Predictors of HBsAg loss were older age and lower baseline HBsAg level (HR for HBsAg loss at 28years 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<100IU/mL compared to HBsAg>10,000IU/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 15years: 0.87 (95% CI 0.82-0.93) versus 0.73 (95% CI 0.66-0.80) (p<0.0001) and AUROC at 28years: 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 28years is HBsAg<10,000IU/mL (sensitivity 72%, specificity 64%, NPV 88%). 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 28years and superior to HBV DNA.