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BACKGROUND & AIMS: Nucleos(t)ide analogues (NUCs) are the standard and mostly lifelong treatment for chronic HBeAg-negative hepatitis B, as functional cure (loss of HBsAg) is rarely achieved. … Discontinuation of NUC treatment may lead to functional cure; however, to date, the evidence for this has been based on small or non-randomized clinical trials. The STOP-NUC trial was designed with the aim of increasing the HBsAg loss rate using a NUC treatment interruption approach. METHODS: In this multicenter, randomized-controlled trial, 166 HBeAg-negative patients with chronic hepatitis B on continuous long-term NUC treatment, with HBV DNA <172 IU/ml (1,000 copies/ml) for >/=4 years, were randomized to either stop (Arm A) or continue NUC treatment (Arm B) for a 96-week observation period. In total, 158 patients were available for final analysis, 79 per arm. The primary endpoint was sustained HBsAg loss up to week 96. RESULTS: Our study met its primary objective by demonstrating HBsAg loss in eight patients (10.1%, 95% CI 4.8%-19.5%) in Arm A and in no patient in Arm B (p = 0.006). Among patients with baseline HBsAg levels <1,000 IU/ml, seven (28%) achieved HBsAg loss. In Arm A, re-therapy was initiated in 11 (13.9%) patients, whereas 32 (40.5%) patients achieved sustained remission. A decrease of HBsAg >1 log IU/ml was observed in 16 patients (20.3%) in Arm A and in one patient (1.3%) in Arm B. No serious adverse events related to treatment cessation occurred. CONCLUSIONS: Cessation of NUC treatment was associated with a significantly higher rate of HBsAg loss than continued NUC treatment, which was largely restricted to patients with end of treatment HBsAg levels <1,000 IU/ml. IMPACT AND IMPLICATIONS: As HBeAg-negative patients with chronic hepatitis B on nucleos(t)ide analogues (NUCs) rarely achieve functional cure, treatment is almost always lifelong. The STOP-NUC trial was conducted to investigate whether discontinuing long-term NUC treatment can increase the cure rate. We found that some patients achieved functional cure after stopping NUCs, which was especially pronounced in patients with HBsAg levels <1,000 at the end of NUC treatment, and that many did not need to resume therapy. The results of the Stop-NUC trial provide evidence for the concept of stopping NUC treatment as a therapeutic option that can induce functional cure.
Authors: F. van Bommel, K. Stein, R. Heyne, J. Petersen, P. Buggisch, C. Berg, S. Zeuzem, A. Stallmach, M. Sprinzl, E. Schott, A. Pathil-Warth, U. von Arnim, V. Keitel, J. Lohmeyer, K. G. Simon, C. Trautwein, A. Trein, D. Huppe, M. Cornberg, F. Lammert, P. Ingiliz, R. Zachoval, H. Hinrichsen, A. Zipprich, H. Klinker, J. Schulze Zur Wiesch, A. Schmiedeknecht, O. Brosteanu, T. Berg
Date Published: 18th Apr 2023
Publication Type: Journal
PubMed ID: 37062574
Citation: J Hepatol. 2023 May;78(5):926-936. doi: 10.1016/j.jhep.2022.12.018. Epub 2023 Mar 28.
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