Z Gastroenterol 2013; 51 - K103
DOI: 10.1055/s-0033-1352743

Stopping long-term NUCs therapy before HBsAg loss in HBeAg negative patients: follow-up of long-term responders

J Petersen 1, P Buggisch 1, H Hinrichsen 2, S Mauss 3, T Berg 4, M Cornberg 5, A Stoehr 1
  • 1IFI Institute for Interdisciplinary Medicine at the Asklepios Clinics St. Georg Hamburg, Liver Unit, Hamburg, Germany
  • 2Gastroenterologische Schwerpunktpraxis, Kiel, Germany
  • 3Hepatogastroenterologische Schwerpunktpraxis, Düsseldorf, Germany
  • 4University, Leipzig, Germany
  • 5Medical High School Hannover, Gastroenterology, Hannover, Germany

Background and aim: Long-term treatment with nucleos(t)ide analogues (NUC) is highly effective but HBsAg loss is a rare event in HBeAg-negative patients. Small pilot trials have challenged the question of sustained remission after discontinuation of long-term NUC-therapy in some patients. We recently reported on high relapse rates (72%) after treatment discontinuation in 32 HBeAg-negative patients (AASLD 2011). Here we report on the long-term outcome of patients without HBV relapse after stopping antiviral treatment after 37 – 80 months.

Methods: 9/32 patients without relapse were identified by retrospective data base search. These patients were prospectively followed (median 30 months).

Results: All patients were HBeAg-negative, 7/9 male, median age 43 years, genotype A or D. Three patients had received lamivudine, two adefovir, one telbivudine, and three entecavir. At stopping treatment all responder patients showed qHBsAg levels of < 1000IU/ml, seven lost HBsAg off therapy (at months 6, 9, 12, 14, 20, 28, 32) and three of these developed anti-HBs (16, 18, 26 months after treatment termination). All nine patients showed an ongoing reduction of qHBsAg levels, demonstrated long-term normal or close to normal ALT-levels, with HBV-DNA ranging from undetectable levels to 6.9 × 103 log IU/ml. No patient displayed apparent liver disease progression by regular fibroscan measurements, whereas a trend towards improvement (albeit not significant) could be detected.

Conclusions: Stopping long-term NUC therapy in HBeAg-negative CHB patients with non-advanced liver disease might be an option for patients with HBsAg titers < 1000 IU/ml. These results suggest that these patients may have developed some degree of immunological control of HBV during and off-treatment. Quantification of HBsAg in patients during long-term antiviral therapy might help to define treatment responders but immunological characterization of CHB patients with an indication for antiviral treatment is urgently needed to better identify predictive markers to stop otherwise indefinite NUC-therap in HBeAg negative patients.