Introduction Tenofovir Disoproxil Fumarate (TDF) is a potent and effective oral antiviral used to treat Chronic Hepatitis B (CHB), but concerns remain about possible long-term toxicity and the costs of indefinite use. An induction-maintenance treatment strategy may allow the use of combination Lamivudine (LAM) and TDF, to avert the development of resistance, followed by maintenance of viral suppression with LAM. To date, there are no data on such a step-down strategy in HBeAg negative CHB. Here we report on patients in whom we safely discontinued TDF, while maintaining viral suppression and normal liver biochemistry.
Methods We selected patients who were had received combination therapy for a minimum of 18 months. Selection criteria included HBeAg negative disease, fibrosis score of <4/6 on biopsy, undetectable HBV DNA and normal serum ALT for a minimum of 12 consecutive months. Patients meeting these criteria were invited to stop TDF and step-down to maintenance LAM monotherapy. Patients were followed at monthly intervals to determine whether viral suppression and ALT normalisation was maintained in the absence of TDF.
Results 21 patients (13 male), median age 47, (range 39–62) discontinued TDF. Median follow-up was 3 months (range 1–10 months). During monthly follow-up biochemical and serological data have been measured. All patients had undetectable HBV DNA prior to step-down therapy to LAM and this remained undetectable during follow-up. Pre-discontinuation of TDF the median ALT was 27 (range 15–38) and during follow-up, on LAM monotherapy, was 22 (range 15–45), (p=NS). Median HBsAg level pre-discontinuation of TDF was log 3.48 (range 1.55–4.49) and 3.49 (range 1.55–4.55), (p=NS) on LAM monotherapy.
Conclusion We demonstrate no viral breakthroughs or biochemical flares on discontinuing TDF. These data suggest that an induction-maintenance strategy may be pursued in selected CHB patients to avoid long-term exposure to TDF and reduce the burden on healthcare budgets in the context of lifelong oral antiviral therapy.
Competing interests None declared.