Stopping Tenofovir Disoproxil Fumarate (TDF) treatment after long term virologic suppression in HBeAg-negative CHB: Week 48 interim results from an ongoing randomized, controlled trial („FINITE CHB“)

Background and Aims: Long-term effective NUC therapy may lead to partial restoration of HBV-specific T cell functions. Stopping therapy in HBV-DNA suppressed HBeAg-negative patients may lead to initial viral rebound and hepatic flare followed by HBsAg clearance. We investigated HBsAg kinetics after controlled stopping of long-term TDF therapy.

Methods: Subjects on effective TDF therapy for at least 4 years were randomized to either stop or to continue TDF for 144 weeks (advanced fibrosis/cirrhosis excluded). Primary endpoint is HBsAg loss at W144. TDF could be restarted in case of clinically significant hepatitis B flares.

Results: 45 subjects were randomized in this open-label study at 13 sites in Germany. 21 Stop-TDF and 21 Continue-TDF subjects completed W48 (n = 3 withdrew consent- data excluded). At W48, Continue-TDF subjects maintained viral suppression, stable ALT, none lost HBsAg. 19 of 21 Stop-TDF subjects had early (first 12 weeks) substantial HBV DNA rebound (median 205,380 IU/mL, [Q1 59,995 IU/mL; Q3: 444,147 IU/mL]) accompanied by ALT elevations (median 106 IU/mL; [Q1 76 IU/ml; Q3 233 IU/mL]). 2 subjects had minimal HBV DNA rebound (max 259 IU/mL) and normal ALT; both had HBsAg levels 1 log (n = 5, median -1.62 log) compared those with decline.

Conclusion: Stopping TDF in chronic HBV HBeAg negative long-term suppressed subjects with defined restarting criteria appears to be safe and led to a significantly greater early HBsAg decline as compared to continued TDF monotherapy. HBsAg loss was observed so far in two subjects (9.5%). If necessary, TDF can be effectively restarted. Lower HBsAg level at BL seems to be a predictive factor for HBsAg decline.