OBJECTIVE: Little is known about the long-term clinical outcome and durability of HBsAg seroclearance following nucleos(t)ide analogue (NUC) therapy in patients with chronic hepatitis B (CHB). DESIGN: During a median follow-up period of 6 years (33 567 patient-years) of 5409 CHB patients who were initially treated with lamivudine or entecavir, a total of 110 achieved HBsAg seroclearance (0.33% annual seroclearance rate) and were included in this study. RESULTS: Baseline alanine aminotransferase (ALT) level >5 times of upper limit of normal was associated with higher probability of HBsAg seroclearance (HR 1.80, p<0.01), while HBeAg positivity (HR 0.46, p<0.01), high HBV DNA level (log(10) IU/mL; HR 0.61, p<0.01), and cirrhosis (HR 0.48, p<0.01) were inversely associated with the probability of HBsAg seroclearance by multivariable analysis. During follow-up for 287 patient-years after HBsAg seroclearance, only two patients with baseline cirrhosis developed hepatocellular carcinoma (HCC) or died (0.7% annual risk), which was of a significantly lower rate compared with propensity score-matched patients without HBsAg seroclearance (HR 0.09, p<0.01). HBsAg reversion and/or HBV DNA reversion occurred in 18 patients, most of which were transient with extremely low serum levels of HBsAg (0.05-1.00 IU/mL) and HBV DNA (17-1818 IU/mL). None required retreatment. The cumulative probability of anti-HBs seroconversion (detection of anti-HBs) at 4 years was 67.4% by Kaplan-Meier analysis. Selection for lamivudine-resistance HBV mutants during treatment was not associated with composite reversion (p=0.66). CONCLUSIONS: HBsAg seroclearance achieved after NUC treatment was associated with favourable clinical outcomes and was durable in most cases during long-term follow-up. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
OBJECTIVE: Little is known about the long-term clinical outcome and durability of HBsAg seroclearance following nucleos(t)ide analogue (NUC) therapy in patients with chronic hepatitis B (CHB). DESIGN: During a median follow-up period of 6 years (33 567 patient-years) of 5409 CHB patients who were initially treated with lamivudine or entecavir, a total of 110 achieved HBsAg seroclearance (0.33% annual seroclearance rate) and were included in this study. RESULTS: Baseline alanine aminotransferase (ALT) level >5 times of upper limit of normal was associated with higher probability of HBsAg seroclearance (HR 1.80, p<0.01), while HBeAg positivity (HR 0.46, p<0.01), high HBV DNA level (log(10) IU/mL; HR 0.61, p<0.01), and cirrhosis (HR 0.48, p<0.01) were inversely associated with the probability of HBsAg seroclearance by multivariable analysis. During follow-up for 287 patient-years after HBsAg seroclearance, only two patients with baseline cirrhosis developed hepatocellular carcinoma (HCC) or died (0.7% annual risk), which was of a significantly lower rate compared with propensity score-matched patients without HBsAg seroclearance (HR 0.09, p<0.01). HBsAg reversion and/or HBV DNA reversion occurred in 18 patients, most of which were transient with extremely low serum levels of HBsAg (0.05-1.00 IU/mL) and HBV DNA (17-1818 IU/mL). None required retreatment. The cumulative probability of anti-HBs seroconversion (detection of anti-HBs) at 4 years was 67.4% by Kaplan-Meier analysis. Selection for lamivudine-resistance HBV mutants during treatment was not associated with composite reversion (p=0.66). CONCLUSIONS: HBsAg seroclearance achieved after NUC treatment was associated with favourable clinical outcomes and was durable in most cases during long-term follow-up. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Christine I Wooddell; Man-Fung Yuen; Henry Lik-Yuen Chan; Robert G Gish; Stephen A Locarnini; Deborah Chavez; Carlo Ferrari; Bruce D Given; James Hamilton; Steven B Kanner; Ching-Lung Lai; Johnson Y N Lau; Thomas Schluep; Zhao Xu; Robert E Lanford; David L Lewis Journal: Sci Transl Med Date: 2017-09-27 Impact factor: 17.956