Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen–negative chronic hepatitis B

Abstract

The incidence of HBsAg seroclearance after stopping Nuc was much higher than that during therapy and highest in patients without virologic and clinical relapse; patients with clinical relapse who remained untreated had a 7.34 times higher incidence of HBsAg clearance than those who received retreatment, suggesting that transient untreated clinical relapse may drive sufficient immune control to functional cure. (Hepatology 2017).

The safety of stopping nucleos(t)ide analogue treatment in patients with HBeAg‐negative chronic hepatitis B

“…Despite the different rates of HBsAg seroclearance in European and Asian cohorts, hepatitis flare played an important role in both studies, which was almost the prerequisite for HBsAg seroclearance. In the Taiwanese study, untreated hepatitis flare increased the incidence of HBsAg seroclearance for 7.34 times, suggesting that transient hepatitis may drive sufficient immune control to achieve functional cure . However, during the long‐term follow‐up of the patients who stopped NA in our previous study, none of the patients cleared HBsAg even after a median follow‐up of 5.1 ± 0.4 years (unpublished data).…”

“…Stopping NA in CHB patients has been a hot topic over the last few years, as it may induce “good flare” which subsequently leads to dramatic HBsAg decline or even HBsAg seroclearance . APASL guidelines recommended to consider stopping NA after 2 years of NA treatment with the three 6 monthly consecutive serum HBV DNA measurements are negative.…”

“…Even so, the annual incidence of pegIFN‐induced HBsAg seroclearance varies from 2.6% to 4.4% in Western countries, but of a much lower annual incidence of 0.46% in Asia . The difference between the East and the West is further elaborated by the very different rates of HBsAg seroclearance (13% in 6 years in a Taiwanese cohort vs 19% in 2 years in a German cohort) in 2 recent studies involving patients who stopped NA treatment . On the other hand, the common observation in these 2 studies was that hepatitis flare was the key factor leading to HBsAg seroclearance …”

Hepatitis B Treatment: What We Know Now and What Remains to Be Researched

“…Recent studies suggest paradoxically that, for patients who are HBeAg‐negative who had been virally suppressed for >2 to 3 years, withdrawal of an NA may be associated with a higher rate of HBsAg loss compared to those who continued the NA . This has led the APASL and EASL guidelines to include a provision for such an approach as long as patients agree to close monitoring after treatment is discontinued.…”

“…However, overly rigorous or prolonged immune lysis of infected hepatocytes can result in liver failure. Moreover, this same study showed that patients who had no viral relapse and those who had viral but not clinical relapse had higher rates of HBsAg loss than those who had clinical relapse, indicating that hepatitis flares are not required for HBsAg loss …”