Nucleos(t)ide withdrawal vs Nucleos(t)ide withdrawal with adjuvant pegylated-interferon in HBeAg-negative hepatitis B virus infection (NUC-B Trial)
Mark Thursz, Maud Lemoine, Ashley Brown, Ivana Carey, Jack Message, Patrick Kennedy, Daniel Forton, Martin Wiselka, Mark Aldersley, Martin Prince, Stuart McPherson, Sandra Phillips, Shilpa Chokshi, Alice Burton, Mala Maini, Johannes Christiaan Botha, Eleni Nastouli, Samantha Tsao, Emanuela Falaschetti, Hanna Box, Mariam Habib, Kaushik Agarwal,Background:
Finite therapy resulting in sustained hepatitis B surface antigen (HBsAg) loss for patients with chronic HBV infection (CHB) is an important therapeutic goal. In patients with HBeAg-negative infection, nucleos(t)ide analogue (NA) withdrawal may achieve HBsAg loss in 5-20% of patients after 3 years. Pegylated interferon (PEG-IFNa) is a recognised treatment for CHB.
Methods:
NUC-B was a randomised, multi-centre trial in NA-treated non-cirrhotic HBeAg negative patients with CHB. Patients were allocated to either NA withdrawal alone (control) or NA withdrawal followed by a 16 week course of PEG-IFNa 180ug weekly commencing 4 weeks after NA cessation (PEG-IFNa). The primary endpoint was HBsAg loss at 3 years.
Results:
The target recruitment of 240 patients was not achieved. 156 patients, 82 to control arm , 74 to PEG-IFNa arm , were recruited between 2017 and 2021; median age 45 years, 24% female, HBV Genotypes -A 16%, B 6%, C 4%, D 24%, E 22%, other 1%, unknown 26%. At 3 years 3% of patients in the contol arm and 14% of patients in the PEG-IFNa arm lost HBsAg (odds ratio 5.39; 95% confidence interval, (1.11, 26.19);
Conclusions:
The use of adjuvant PEG-IFNa therapy after withdrawal of NA therapy increases the rate of HBsAg loss whilst simultaneously reducing the number of exaggerated flares.