Efficacy and Safety of Tenofovir Disoproxil Fumarate Cessation in Chronic Hepatitis B: A Prospective Cohort Study in Iran.

Abstract

Background: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment of chronic hepatitis B (CHB) due to its high antiviral potency and genetic barrier to resistance. However, long-term use is associated with renal toxicity, bone mineral loss, and high treatment burden. The European Association for the Study of the Liver (EASL) 2017 guidelines allow for cessation of nucleoside analogues (NAs) in well-selected patients, but data on outcomes following TDF withdrawal in Middle Eastern populations remain limited.

Methods: In this prospective cohort study, 44 Iranian patients with CHB who fulfilled the 2017 EASL criteria for safe TDF discontinuation were followed for 12 months. Virological failure was defined as HBV DNA >2000 IU/mL (HBeAg-negative) or >20000 IU/mL (HBeAg-positive). Biochemical failure was defined as alanine aminotransferase (ALT) >2× upper limit of normal (ULN). Patients were assessed quarterly through laboratory testing and imaging. Outcomes, relapse timing, and predictors of failure were evaluated.

Results: TDF discontinuation was successful in 22 patients (50%) who maintained both virological suppression and normal ALT without reinitiation of therapy. Relapse occurred in the remaining 22 patients, with most failures (81.8%) occurring within the first 6 months. No cases of hepatic decompensation were reported. Virological relapse was more frequent than biochemical relapse. Serum creatinine significantly improved post-cessation (1.14 ± 0.30 to 1.10 ± 0.28 mg/dL, P=0.05), and liver stiffness remained stable in 97.7% of patients (fibro scan result). Longer HBV infection duration and extended TDF treatment were significant predictors of relapse.

Conclusion: TDF cessation in appropriately selected Iranian patients with CHB is safe and feasible, with half maintaining remission over 12 months. Relapse predominantly occurred early and was mild, supporting EASL 2017 guideline recommendations. These findings offer valuable insight into TDF discontinuation in genotype D-predominant populations and support the use of finite therapy strategies with careful post-withdrawal monitoring.