Nucleos(t)ide withdrawal vs Nucleos(t)ide withdrawal with adjuvant pegylated-interferon in HBeAg-negative hepatitis B virus infection (NUC-B Trial)

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); p=0.037). In the control arm 34.9% of patients returned to NA therapy compared to 28.4% in the PEG_IFNa- arm. Exaggerated flares occurred in 27.9% of patients in the control arm compared with 13.4% in the PEG-IFNa arm. 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.