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DOI: 10.1055/s-0040-1716038
Response to discontinuation of nucleos(t)ide analogue treatment in HBeAg-negative chronic hepatitis B: results from the Stop-NUC trial
Background and aims Discontinuation of long-term suppression of HBV replication with nucleos(t)ide analogues (NUCs) can result in durable immune control of hepatitis B virus (HBV) replication in HBeAg negative patients. We have assessed the effect of NUC discontinuation in HBeAg negative patients in a prospective, multicenter, randomized trial (the Stop-NUC study).
Method HBeAg-negative patients without cirrhosis who had achieved suppressed HBV DNA for ≥4 years during NUC therapy were randomly assigned to either stop (Arm A) or continue (Arm B) treatment. The primary endpoint was sustained HBsAg loss at week 96. Secondary end points included HBsAg seroconversion, virologic response (HBV DNA ≤ 20 IU/mL), biochemical response, (alanine aminotransferase (ALT) < upper level normal (ULN)) anumber of ALT flares (ALT > 3 ULN) and time to re-therapy in the non-treatment arm. All patients were observed for 96 weeks. In each arm 83 patients were randomized. The full analysis set comprised 158 patients (79 vs 79).
Results At week 96 after NUC discontinuation, HBsAg loss or seroconversion were found in 8/79 (10 %) and 6/79 (8 %) patients in Arm A and in no patient in Arm B, respectively (p =0.006 and p =0.028). After NUC discontinuation, all patients in Arm A and no patient in Arm B experienced an HBV DNA flare, however, at week 96 HBV DNA were levels ≤ 20 IU/mL in 24/79 (31 %) patients in Arm A and in all patients in Arm B (p < 0.001). ALT flare occurred in 28/79 (35 %) patients in Arm A and in no patient in Arm B, and ALT levels were within normal ranges in 69/79 (88 %) patients in Arm A and in 77/79 (97 %) patients in Arm B at week 96 (p =0.032). Re-treatment with NUCs due to severe ALT flares had to be reinstalled in 11/79 (14 %) of patients in Arm A. At week 96, 8/79 (10 %) patients had HBsAg loss, and in addition 54/79 (68 %) patients had no indication for treatment according to current EASL recommendations. No patient in Arm A suffered any serious adverse event possibly related to discontinuation of NUC therapy.
Conclusion This first large-scale randomized study demonstrates the potential of discontinuation of long-term NUC treatment for induction of durable immune control and functional cure in patients with HBeAg negative chronic hepatitis B (EudraCT-Nr.: 2013-004882-15).
Publikationsverlauf
Artikel online veröffentlicht:
08. September 2020
© Georg Thieme Verlag KG
Stuttgart · New York