Stopping long-term nucleos(t)ide analogue therapy before HBsAg loss or seroconversion in HBeAg negative CHB patients: experience from five referral centers in Germany
AASLD 2011 abstract 1417. Stopping long-term nucleos(t)ide analogue therapy before HBsAg loss or seroconversion in HBeAg negative CHB patients: experience from five referral centers in Germany
J. Petersen1; P. Buggisch1; A. Stoehr1; H. Hinrichsen2; S. Mauss3; T. Berg4; K. Port5; M. P. Manns 5; H. Wedemeyer 5
1. Asklepiosklinik St. Georg, Liver Center Hamburg IFI Institute, Hamburg, Germany.
2. Gastroenterology, Gastroenterologische Schwerpunkt Praxis, Kiel, Germany.
3. Hepatology Center, Gastroenterologische Schwerpunktpraxis, Dusseldorf, Germany.
4. Gastroenterology and Hepatology, University of Leipzig, Leipzig, Germany.
5. Gastroenterology and Hepatology, Hanover Medical School, Hanover, Germany.
Background and aim: Long-term treatment with nucleos(t)ide analogues (NUCs) is highly effective but associated with increasing rates of side effects and nonadherence. HBsAg loss or seroconversion is a rare event in HBeAg negative patients. Small pilot trials have challenged the question of a sustained biochemical and virological remission after discontinuation of long-term NUC therapy in some HBeAg negative patients. Here we report on relapse rates of HBV DNA, ALT flares, re-therapy rates and HBsAg loss in CHB patients without advanced liver disease after stopping NUC therapy after long-term viral suppression (3-7 yrs).
Methods: Retrospective data base search. 32 patients were identified in which NUC therapy was stopped, 14 pts during lamivudin, 7 adefovir, 6 telbivudine, 5 entecavir. All patients were HBeAg negative, 66 % male, median age 47 years. All patients showed durable suppression of HBV DNA for NUC therapy in between 3-7yrs (2000 IU/ml) and biochemical hepatitis flares (ALT levels 2.2-7 x ULN) and were restarted on antiviral therapy in between one month and 12 months after stopping therapy. 9 patients remained without antiviral therapy (3 after Lam-, two after ADV-, one after LdT therapy, 3 after entecavir). Of those nine patients, the majority showed HBsAg levels of less than 1000IU/ml at stopping point, four lost HBsAg off therapy (6, 9, 12, 14 months), two of those developed anti-HBs (16,18 months after termination of therapy). All nine patients demonstrated normal or close to normal ALT levels with HBV-DNA ranging from undetectable levels to 4.6x106 log copies/ml. All nine patients showed no apparent progress of liver disease.
Conclusion: Stopping long-term NUC therapy in HBeAg negative CHB patients with non-advanced liver disease might be an option for some patients, especially in those with low HBsAg titers. Immunological characterization of these patients and prospective studies investigating termination of NUC therapy are urgently needed