NUC discontinuation shows durable immune control in e antigen-negative hepatitis B

Discontinuation of long-term nucleos(t)ide analogues has the potential to induce durable immune control and functional cure in patients with e antigen-negative, or HBeAG, chronic hepatitis B, according to a presenter at The Digital International Liver Congress.

In his presentation, Florian van Bömmel, from University Hospital Leizig in Germany, said that discontinuing nucleos(t)ide analogues (NUCs) can result in durable control of HBV replication in patients without HBeAg. He and his colleagues sought to assess this effect in a prospective, randomized trial called The Stop-NUC study.

Researchers included patients who were HBeAg negative without cirrhosis who had achieved suppressed HBV DNA for at least 4 years during NUC therapy. They randomly assigned patients to either stop (arm A, n = 79) or continue NUC therapy (arm B, n = 79). The primary endpoint of the study was sustained hepatitis B surface antigen (HBsAG) loss at week 96, and investigators also explored several secondary endpoints, including HBsAg seroconversion and virologic response.

At week 96, eight patients in arm A achieved HBsAg loss and six achieved seroconversion compared with none in arm B (P = .006 and P = .028).

All patients in arm A experienced an HBV DNA flare greater than 20 IU/mL compared with none in arm B. However, at week 96, HBV DNA were levels no more than 20 IU/mL in 24/79 (31%) patients in arm A and in all patients in arm B (P < .001). Additionally, 35% of patients in arm A experienced alanine aminotransferase (ALT) flare compared with none in arm B, and ALT levels were within normal ranges in 88% of patients in arm A and 97% in arm B.

Although 14% of patients in arm A had to restart NUC therapy, 68% had no indication for treatment according to current guidelines. No patients in arm A had a serious adverse event related to NUC discontinuation.

“This is the first large-scale randomized study demonstrating the potential of discontinuation of long-term treatment for induction of durable control and functional cure in patients [who were] e-antigen negative,” van Bömmel said. “A follow-up at greater than 24 months after stopping NUCs is mandatory to assess the efficacy of NUC discontinuation, as HB surface antigen losses occurred during the whole observation. Therefore, the Stop-NUC trial will be continued.”