ABSTRACT FINAL ID: 1860
TITLE: 4-year outcomes after cessation of tenofovir in immune-tolerant chronic hepatitis B patient
SPONSORSHIP - THIS STUDY WAS SPONSORED BY: (IF THIS ABSTRACT WAS NOT SPONSORED PLEASE INDICATE):
The original trial was supported by Gilead Sciences, but the investigators have not received additional support for this follow-up study.
Background: With emerging efficacy and safety data, some patients with immune-tolerant chronic hepatitis B may receive temporary antiviral therapy (e.g. to prevent vertical transmission of hepatitis B virus [HBV]). The long-term outcome after cessation of antiviral therapy in such patients is unknown.
Methods: This was a follow-up study of a phase 2 trial at 2 Hong Kong centers (NCT00507507). Immune-tolerant patients were randomized to receive tenofovir disoproxil fumarate (TDF) or TDF plus emtricitabine (FTC) for 4 years. Patients who discontinued TDF±FTC were followed for another 4 years. Virological relapse was defined as HBV DNA >2000 IU/ml; clinical relapse was defined as HBV DNA >2000 IU/ml and alanine aminotransferase (ALT) >2 times the upper limit of normal (ULN).
Results: 20 patients stopped treatment (age 36±9; 65% females; 10 treated with TDF and 10 with TDF+FTC; 10 genotype B and 10 genotype C) and were followed for 206±14 weeks. All patients developed virological relapse at post-treatment Week 4 (HBV DNA 7.07±1.45 log IU/ml). 10 (50%) patients developed clinical relapse at 15±11 weeks, among whom 6 had ALT >5 times ULN and 3 had ALT >10 times ULN (highest 1149 U/l). All patients with clinical relapse had the first ALT elevation at or before Week 24. No patient developed liver decompensation or hepatocellular carcinoma. 11 (55%) patients were restarted on antiviral therapy (7 on entecavir and 4 on TDF); 4 achieved complete HBV DNA suppression, 10 had ALT normalization, and 1 achieved hepatitis B e antigen (HBeAg) seroconversion. Among the 9 patients not restarted on therapy, 2 patients had HBeAg seroconversion at week 45 and month 33, with normal ALT and HBV DNA of 7.12 log IU/ml and 1.62 IU/ml, respectively. The remaining 7 untreated patients continued to have positive HBeAg, high HBV DNA (8.50±0.34 log IU/ml) and normal ALT for 196±18 weeks post-treatment.
Conclusions: Rapid virological relapse is universal and clinical relapse is common after stopping antiviral therapy in patients with immune-tolerant chronic hepatitis B. Treatment initiation and cessation do not enhance HBeAg seroconversion. Therefore, immune-tolerant patients should only be treated when there are strong indications. If temporary antiviral therapy is needed, a drug with high genetic barrier to resistance should be used, and liver biochemistry should be monitored closely for at least 6 months after treatment cessation.