Tenofovir Cessation After Long-Term Treatment in HBV-Infected Patients Associated With Greater Decline in HBsAg:: Presented at EASL

By Chris Berrie

VIENNA, Austria -- April 29, 2015 -- Stopping tenofovir disoproxil fumarate treatment after long-term virologic suppression is safe and associated with a more profound decline in hepatitis B surface antigen (HBsAg) levels than continuous treatment in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who have undetectable hepatitis B virus (HBV) DNA, according to a study presented here at the International Liver Congress, the 50th Annual Meeting of the European Association for the Study of the Liver (EASL).

For patients with HBeAg-negative CHB, optimal nucleos(t)ide therapy duration remains to be defined. The various guidelines recommend long-term nucleos(t)ide therapy until HBsAg loss is reached.

However, “although long-term nucleos(t)ide therapy may partially restore HBV-specific T-cell function, HBsAg loss is rarely achieved in HBeAg-negative patients,” said Thomas Berg, MD, Hepatology Section, Internal Medicine, Leipzig University, Leipzig, Germany, on April 25.

This open-label trial investigated the results of cessation of treatment with the nucleotide analogue reverse transcriptase inhibitor tenofovir disoproxil fumarate after ≥4 years of therapy in HBeAg-negative CHB patients. Inclusion criteria were HBV DNA <400 copies/mL for at least 3 years, with no cirrhosis, and normal alanine transaminase (ALT).

The patients were randomised to continue tenofovir disoproxil fumarate therapy (TDF-continue group; n = 21; median age, 46 years; 71% male) or to stop tenofovir disoproxil fumarate therapy (TDF-stop group; n = 21; median age, 44 years; 86% male). Baseline clinical characteristics were similar in the 2 groups.

In this interim analysis, Dr. Berg noted 3 patients (14%) in the TDF-stop group who restarted tenofovir disoproxil fumarate. Two experienced early flare, and the third experienced persistent high-level viremia without flare.; After restart of the treatment, the patients returned to normal ALT and undetectable HBV DNA levels by week 48.

HBV DNA became detectable in all patients in the TDF-stop group, with a median of 5.32 log10 IU/mL up to week 48. At week 48, 89% had HBV DNA levels of <20,000 IU/mL, with 78% at <2,000 IU/mL. Over this period, only 1 patient (5%) in the TDF-continue group had detectable HBV DNA.

In the TDF-stop group, ALT peaked at >2 times the upper limit of normal (ULN) in 57% of patients, with an overall median of 162 IU/L at week 48. Excluding the 3 restart patients, all patients in this group had ALT <2 times ULN and 83% had levels below ULN. The ALT profiles in the TDF-continue group remained unchanged.

Compared with the TDF-continue group, the TDF-stop group had a more pronounced reduction in mean HBsAg levels at week 48 (0.11 vs 0.77 log10 reduction). There were no significant changes in mean HBsAg levels in the TDF-continue group, with no HBsAg losses.

Overall for the TDF-stop group, at 48 weeks from discontinuation, HBsAg loss was seen in 2 patients (10%), and 57% showed HCV DNA <2,000 IU/mL with ALT <2 times ULN, whereas only 19% showed HCV DNA >2,000 IU/mL and ALT >2 times ULN.

“Sixty-seven percent of patients had a profile not indicative for antiviral treatment,” said Dr. Berg.

“These data do support the concept of stopping antiviral therapy in long-term HBV DNA-suppressed subjects without cirrhosis,” he concluded.

Funding for the study was provided by Gilead Sciences, Inc.

[Presentation title: Stopping Tenofovir Disoproxil Fumarate Treatment After Long-Term Virologic Suppression in HBeAg-Negative CHB: Week 48 Interim Results From an Ongoing Randomized, Controlled Trial (“FINITE CHB”). Abstract O119]

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