Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study

Background & Aims: There is currently no virological cure for chronic hepatitis B but successful nucleos(t)ide analogue (NA) therapy can suppress hepatitis B virus (HBV) DNA replication and, in some cases, result in HBsAg loss. Stopping NA therapy often leads to viral relapse and therefore life-long therapy is usually required. This study investigated the potential to discontinue tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Methods: Non-cirrhotic HBeAg-negative patients who had received TDF for >= 4 years, with suppressed HBV DNA for >= 3.5 years, were randomly assigned to either stop (n = 21) or continue (n = 21) TDF monotherapy. Standard laboratory tests including HBV DNA viral load, HBsAg and alanine aminotransferase (ALT) measurements, and adverse event reporting were carried out during treatment and post-treatment follow-up for 144 weeks. Results: Of the patients who stopped TDF therapy, 62% (n = 13) remained off-therapy to Week 144. Median HBsAg change in this group was -0.59 log(10)IU/ml (range -4.49 to 0.02 log(10)IU/ml) vs. 0.21 log(10)IU/ml in patients who continued TDF therapy. Four patients (19%) achieved HBsAg loss. Patients stopping therapy had initial fluctuations in viral load and ALT; however, at Week 144, 43% (n = 9) had either achieved HBsAg loss or had HBV DNA <2,000 IU/ml. There were no unexpected safety issues identified with stopping TDF therapy. Conclusions: This controlled study demonstrated the potential for HBsAg loss and/or sustained virological response in noncirrhotic HBeAg-negative patients stopping long-term TDF therapy. Lay summary: Nucleos(t) ide analogue (NA) is usually a life-long therapy for HBV patients. This randomised controlled study investigated the discontinuation of tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Of the patients who stopped TDF therapy, 62% remained off-therapy to Week 144, of which 43% of patients had achieved either HBsAg loss or HBV DNA <2,000 IU/ml. This offers a potential for long-term HBV-suppressed patients without cirrhosis to stop NA therapy under strict surveillance. Clinical trial number: NCT01320943. (C)2017 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.